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Mathematical Markup Language (MathML) Version 3.0 3rd Edition

2.3 Conformance

Information nowadays is commonly generated, processed and rendered by software tools. The exponential growth of the Web is fueling the development of advanced systems for automatically searching, categorizing, and interconnecting information. In addition, there are increasing numbers of Web services, some of which offer technically based materials and activities. Thus, although MathML can be written by hand and read by humans, whether machine-aided or just with much concentration, the future of MathML is largely tied to the ability to process it with software tools.

There are many different kinds of MathML processors: editors for authoring MathML expressions, translators for converting to and from other encodings, validators for checking MathML expressions, computation engines that evaluate, manipulate, or compare MathML expressions, and rendering engines that produce visual, aural, or tactile representations of mathematical notation. What it means to support MathML varies widely between applications. For example, the issues that arise with a validating parser are very different from those for an equation editor.

This section gives guidelines that describe different types of MathML support and make clear the extent of MathML support in a given application. Developers, users, and reviewers are encouraged to use these guidelines in characterizing products. The intention behind these guidelines is to facilitate reuse by and interoperability of MathML applications by accurately setting out their capabilities in quantifiable terms.

The W3C Math Working Group maintains MathML Compliance Guidelines. Consult this document for future updates on conformance activities and resources.

2.3.1 MathML Conformance

A valid MathML expression is an XML construct determined by the MathML RelaxNG Schema together with the additional requirements given in this specification.

We shall use the phrase "a MathML processor" to mean any application that can accept or produce a valid MathML expression. A MathML processor that both accepts and produces valid MathML expressions may be able to "round-trip" MathML. Perhaps the simplest example of an application that might round-trip a MathML expression would be an editor that writes it to a new file without modifications.

Three forms of MathML conformance are specified:

  1. A MathML-input-conformant processor must accept all valid MathML expressions; it should appropriately translate all MathML expressions into application-specific form allowing native application operations to be performed.

  2. A MathML-output-conformant processor must generate valid MathML, appropriately representing all application-specific data.

  3. A MathML-round-trip-conformant processor must preserve MathML equivalence. Two MathML expressions are "equivalent" if and only if both expressions have the same interpretation (as stated by the MathML Schema and specification) under any relevant circumstances, by any MathML processor. Equivalence on an element-by-element basis is discussed elsewhere in this document.

Beyond the above definitions, the MathML specification makes no demands of individual processors. In order to guide developers, the MathML specification includes advisory material; for example, there are many recommended rendering rules throughout Chapter 3 Presentation Markup. However, in general, developers are given wide latitude to interpret what kind of MathML implementation is meaningful for their own particular application.

To clarify the difference between conformance and interpretation of what is meaningful, consider some examples:

  1. In order to be MathML-input-conformant, a validating parser needs only to accept expressions, and return "true" for expressions that are valid MathML. In particular, it need not render or interpret the MathML expressions at all.

  2. A MathML computer-algebra interface based on content markup might choose to ignore all presentation markup. Provided the interface accepts all valid MathML expressions including those containing presentation markup, it would be technically correct to characterize the application as MathML-input-conformant.

  3. An equation editor might have an internal data representation that makes it easy to export some equations as MathML but not others. If the editor exports the simple equations as valid MathML, and merely displays an error message to the effect that conversion failed for the others, it is still technically MathML-output-conformant.

2.3.1.1 MathML Test Suite and Validator

As the previous examples show, to be useful, the concept of MathML conformance frequently involves a judgment about what parts of the language are meaningfully implemented, as opposed to parts that are merely processed in a technically correct way with respect to the definitions of conformance. This requires some mechanism for giving a quantitative statement about which parts of MathML are meaningfully implemented by a given application. To this end, the W3C Math Working Group has provided a test suite.

The test suite consists of a large number of MathML expressions categorized by markup category and dominant MathML element being tested. The existence of this test suite makes it possible, for example, to characterize quantitatively the hypothetical computer algebra interface mentioned above by saying that it is a MathML-input-conformant processor which meaningfully implements MathML content markup, including all of the expressions in the content markup section of the test suite.

Developers who choose not to implement parts of the MathML specification in a meaningful way are encouraged to itemize the parts they leave out by referring to specific categories in the test suite.

For MathML-output-conformant processors, information about currently available tools to validate MathML is maintained at the W3C MathML Validator. Developers of MathML-output-conformant processors are encouraged to verify their output using this validator.

Customers of MathML applications who wish to verify claims as to which parts of the MathML specification are implemented by an application are encouraged to use the test suites as a part of their decision processes.

2.3.1.2 Deprecated MathML 1.x and MathML 2.x Features

MathML 3.0 contains a number of features of earlier MathML which are now deprecated. The following points define what it means for a feature to be deprecated, and clarify the relation between deprecated features and current MathML conformance.

  1. In order to be MathML-output-conformant, authoring tools may not generate MathML markup containing deprecated features.

  2. In order to be MathML-input-conformant, rendering and reading tools must support deprecated features if they are to be in conformance with MathML 1.x or MathML 2.x. They do not have to support deprecated features to be considered in conformance with MathML 3.0. However, all tools are encouraged to support the old forms as much as possible.

  3. In order to be MathML-round-trip-conformant, a processor need only preserve MathML equivalence on expressions containing no deprecated features.

2.3.1.3 MathML Extension Mechanisms and Conformance

MathML 3.0 defines three basic extension mechanisms: the element provides a way of displaying glyphs for non-Unicode characters, and glyph variants for existing Unicode characters; the element uses attributes from other namespaces to obtain implementation-specific parameters; and content markup makes use of the attribute, as well as Content Dictionaries and the attribute, to point to external definitions of mathematical semantics.

These extension mechanisms are important because they provide a way of encoding concepts that are beyond the scope of MathML 3.0 as presently explicitly specified, which allows MathML to be used for exploring new ideas not yet susceptible to standardization. However, as new ideas take hold, they may become part of future standards. For example, an emerging character that must be represented by an element today may be assigned a Unicode code point in the future. At that time, representing the character directly by its Unicode code point would be preferable. This transition into Unicode has already taken place for hundreds of characters used for mathematics.

Because the possibility of future obsolescence is inherent in the use of extension mechanisms to facilitate the discussion of new ideas, MathML can reasonably make no conformance requirements concerning the use of extension mechanisms, even when alternative standard markup is available. For example, using an element to represent an 'x' is permitted. However, authors and implementers are strongly encouraged to use standard markup whenever possible. Similarly, maintainers of documents employing MathML 3.0 extension mechanisms are encouraged to monitor relevant standards activity (e.g., Unicode, OpenMath, etc.) and to update documents as more standardized markup becomes available.

2.3.2 Handling of Errors

If a MathML-input-conformant application receives input containing one or more elements with an illegal number or type of attributes or child schemata, it should nonetheless attempt to render all the input in an intelligible way, i.e., to render normally those parts of the input that were valid, and to render error messages (rendered as if enclosed in an element) in place of invalid expressions.

MathML-output-conformant applications such as editors and translators may choose to generate expressions to signal errors in their input. This is usually preferable to generating valid, but possibly erroneous, MathML.

2.3.3 Attributes for unspecified data

The MathML attributes described in the MathML specification are intended to allow for good presentation and content markup. However it is never possible to cover all users' needs for markup. Ideally, the MathML attributes should be an open-ended list so that users can add specific attributes for specific renderers. However, this cannot be done within the confines of a single XML DTD or in a Schema. Although it can be done using extensions of the standard DTD, say, some authors will wish to use non-standard attributes to take advantage of renderer-specific capabilities while remaining strictly in conformance with the standard DTD.

To allow this, the MathML 1.0 specification [MathML1] allowed the attribute on all elements, for use as a hook to pass on renderer-specific information. In particular, it was intended as a hook for passing information to audio renderers, computer algebra systems, and for pattern matching in future macro/extension mechanisms. The motivation for this approach to the problem was historical, looking to PostScript, for example, where comments are widely used to pass information that is not part of PostScript.

In the next period of evolution of MathML the development of a general XML namespace mechanism seemed to make the use of the attribute obsolete. In MathML 2.0, the attribute is deprecated in favor of the use of namespace prefixes to identify non-MathML attributes. The attribute remains deprecated in MathML 3.0.

For example, in MathML 1.0, it was recommended that if additional information was used in a renderer-specific implementation for the element (Section 3.7.1 Bind Action to Sub-Expression ), that information should be passed in using the attribute:

<maction actiontype="highlight" other="color='#ff0000'"> expression </maction>

From MathML 2.0 onwards, a attribute from another namespace would be used:

<body xmlns:my="http://www.example.com/MathML/extensions"> ... <maction actiontype="highlight" my:color="#ff0000"> expression </maction> ... </body>

Note that the intent of allowing non-standard attributes is not to encourage software developers to use this as a loophole for circumventing the core conventions for MathML markup. Authors and applications should use non-standard attributes judiciously.

In boarding the supervisor was offering passengers vouchers because weight restrictions. I couldn't take the morning flight because of the time wasn't suitable for me. I asked the supervisor to put me on a later flight out of JFK so I could leave now and catch that flight. She showed reluctance to do so. Clearly not the service delta wants to provide in this environment with delays.

Delta does a great job. But im now looking for more direct flights in the future. My time is more valuable. I was in the airport/on a plane for 9 hours!

The plane was brand new so did not yet have WiFi installed. Otherwise everything was great for the long flight from Tel Aviv to New York

Timely boarding announcements, fairly roomy seating, and prompt snack delivery. Seats in the waiting area could have USB charging ports on both sides. Minor issue; I charged my phone on the flight.

Seats were surprisingly comfortable and sufficiently roomy. Flight attendants were helpful and courteous. Flight departed on time and arrived a little early. My wife and I both agreed this may have been the best flight we've ever had: a direct flight from Kansas City to Atlanta to visit my son and his family. Convenient, relatively inexpensive, and overall a great experience!

Pros: "Helpful and attentive crew"

Pros: "Crew was super amazing and friendly! Very good service also!"

Cons: "No seat back entertainment.."

Pros: "The best other than the fact it was packed full lol but that’s not Deltas fault"

Pros: "The flight itself was excellent. Friendly, helpful, kind — great attendants and crew."

Cons: "The flight was delayed 4 hours. We never found out why exactly. That was a little tough but staff was great"

Pros: "We were in coach and the crew made us feel like it was business class!"

Pros: "Boarding was very efficient. Flight attendants were helpful and kind and seemed to care."

Cons: "We booked basic seats knowing we might not sit together however we did not know they would separate children. They put my husband and I in an exit row and my daughter at the back of the plane with strangers. I was not comfortable with strangers being responsible for my child. I assumed they would seat children with at least one parent. We did ask to move at the gate and the accommodated us with the last row on the plane. No recline, no window, and right next to the bathrooms. We took it to be with our kid but this policy needs to be revised. Kids should always be seated with the adult responsible for them... who knows what kind of person might end up next to my child. Not to mention if she had needed something is the stranger gonna take care of it? It’s just a bad practice imo."

Pros: "Quick and easy boarding and departing. Wonderful and friendly staff."

Cons: "Honestly, everything was great. Food and entertainment were a little lacking but for a 3 hour flight it was more than acceptable."

Pros: "Great crew, prompt and courteous despite the short flight"

Cons: "Flight departed an hour past scheduled time due to a snafu with flight attendants: they were either absent or really late or a replacement crew. Unacceptable personnel management."

Pros: "Amazing crew"

Pros: "The crew was polite and pleasant unlike the crew from KC to Boston."

Cons: "Telling us to check bags before we get to our seat and find out there is no more room."

Cons: "Just a bunch of weather delays because of the bad storms. I did not like the selection of movies and tv shows on the delta flight. So I just listened to podcast in my phone. But other than that everything was great."

Pros: "Helpful crew."

Cons: "These planes are tiny. Our equipment was B717."

Pros: "Small plane without bells and whistles and no middle seats."

Cons: "The internet would not work. I couldn’t use any of the inflight entertainment."

Pros: "We had the worst flight ever on Delta flight worst Attitude of the flight attendant she was very Rude i even told her she was"

Cons: "We didn't get served nothing to drink until 45 min to kc then by then i was so dehydrated i asked for a can of pop she said NO I SAID REALLY SHE SAID DELTAS NOT IN CHARGE OF STOCKING DRINKS & SNACKS SHE HAD MORE PEOPLE' TO SERVE REALLY EVERBODY IN FRONT OF US GOT WHAT THEY WANTED SO I HAD NOTHIN AT"

Cons: "2nd Delta flight on the same day that was delayed. This one only 44 min."

Pros: "Wonderful friendly crew. Comfy seat. Very pleasantly impressed with the comfort on a CRJ900 -- windows are large and closer to eye level, standing room is enough."

Cons: "Never made it because of my originating flight"

Cons: "The airline cancelled the flight alluring weather conditions, when the reality was they did not wanted the plane to park in Kansas. The weather conditions were even worse on the flight I was moved to, and that flight was not cancelled. They absolutely did not care about the passengers"

Pros: "Overall good experience"

Cons: "Plane 1hr late taking off"

Pros: "Nice people"

Cons: "Waiting at gate in KC"

Pros: "Efficient and friendly"

Pros: "The movies kept my daughter busy."

Pros: "Awesomeness"

Pros: "Professional, courteous, and responsive attendants and flight crew."

Cons: "Nothing."

Pros: "I did not like anything all. But the to last agent to help me after I was send to different airlines"

Cons: "And when I get to US delta Airline ticketr did not even look at my ticket she just send to Virginia Australia make me walk all over. I know it supposed to be delta"

Pros: "The flight was nearly full, but I lucked out. One person in my row did not show up, so myself and the other lady in my row had the benefit of having an open seat in between us. The crew was cheerful and accommodating. They did the normal beverage service, but also brought complimentary water and coffee 3x during the rest of the flight. This was greatly appreciated, especially after 5 days of drinking and partying. My buddies and I spent two and a half days in Las Vegas for a bachelor party followed by two days in the LA area for a wedding (yes we did it Hangover style) :) Thank you Delta!"

Cons: "My only complaint was that the flight was delayed out of LAX by about 30 minutes due to the flight in-bound being delayed. However, the captain made up most of this time in the air so it ended up being a non-issue."

Cons: "We were on the tarmac for almost 2 hours. It's probably LaGuardia but the experience was very bad."

Pros: "Made the best of a overcrowded messy airport"

Pros: "Horrible seats. Scraped up my knees on a screwhead on the seat in front of me. Way too cramped."

Pros: "Boarding was delayed, but flight crew & desk staff moved us quickly through & off we went. It was efficient & well managed."

Cons: "A bit cramped on board. Thinking of the discount carriers while smooshed in with my aisle mates."

Pros: "Big bathrooms, friendly staff, free eyemaks"

Cons: "Delays. Ways late."

Pros: "The service and non stop smooth ride. Boarding was a new experiance taking a bus to the plane. Was quick and crew helpful storing my carryon. Everyone very helpful."

Pros: "Love the free movies and individual screen, and the new seats are more comfortable"

Cons: "That it wasn’t 1970, with full meals and more leg room"

Cons: "Landing was frightening."

Pros: "The quick flight was nice, the flight attendants were super sweet and kind and were willing to give me extra snacks when I requested for them. No screens on this flight, but understandable since it was such a short flight :)"

Cons: "Nothing"

Pros: "Other than the delay by the Hong Kong Airport controller, everything went smoothly. The plane was late to Seattle."

Cons: "The luggage custom clearing would be much better if we could do it like the Vancouver BC where an electronic monitor was used to identify one's luggage without the need to handle them manually. Much more efficient and allowing folks to get on the connecting flights easier."

Pros: "free texting and entertainment!"

Cons: "our flight was delayed half an hour."

Pros: "Crew and landing were fantastic"

Pros: "Nothing."

Cons: "Flight attendant late arriving to his job causing a 30 minute delay in boarding. Desk staff at airport seemed more interested in their own conversations than helping passengers . Fight attendants seemed uninterested in their jobs and lacked warmth. 45 minutes late arriving in Kansas City no announcements from captain"

Pros: "The smootheness of the flight."

Cons: "The fact that the passenger behind me is was kicking the back of my seat. And it wasn't even a child!"

Pros: "The fact that there were no delays!"

Cons: "Nothing"

Pros: "In-flight entertainment (if you brought a tablet or laptop with you), yummy gluten free pretzels, good flight attendants."

Cons: "A complimentary sandwich would have been nice for a 4 hour flight."

Pros: "Flights were on time..."

Cons: "Worst seats ever. Uncomfortable. Didn't recline and were supposed to. Was told by the attendant "that's too bad. It's supposed to" when I mentioned it."

Pros: "The flight attendant. Lovely and professional."

Started with long line for checking, inhospitable customer service (not rude but not friendly), announcement for boarding is so confusing, they called for family with kids, when we proceeded they said no you’re economy so you can’t board which they never specified it when they announced and made us and other families confused. Then the fly attendants professionalism was horrible one of them walk right by me and bump into me while coffee cup in my hands and kept moving like nothing happened, not with even say a word not even a sorry. Food quality went down the hill. I pay more for the RJ every time I fly for the better service quality but this time it’s not. I am not losing money again for RJ and I am so disappointed why would company with good reputation give it up for whatever the reason

Very recommended

It’s was very good and respect and I love it

Cons: "Windows locked dark for whole flight in the DAYTIME going over spectacular scenery in Norway and Greenland. No eye shades given out. Totally depressing. Food very mediocre with nothing Arabic in spite of great Arab food."

Cons: "Let passengers look out the window in the daytime. Going over Norway and Greenland with fantastic scenery and windows are blacked out whole trip. I paid to select a window seat. Totally depressing to be in the dark all day. Windows black even when lunch served. Tasteless Western food. Would have liked something Arab. (I’m a white American)"

Pros: "The crew was nice and courteous. The flight went smoothly. The bathrooms were easily accessible."

Cons: "They barely offered water on the 11-12 hour flights. The crew was not around other than to hand out meals during the first and last few hours."

Pros: "The aircraft is new and the crew are nice"

Cons: "More food and more toilets"

Pros: "Crew attentive, flight left and arrived on time"

Cons: "More movie and TV show options. Also foot rest would have been nice."

Pros: "The flight schedule was better than any other carrier. The flight crew was very helpful."

Cons: "The space between rows really seemed much narrower than a year ago."

Cons: "Didn't think of something because the flight was awesome."

Cons: "I hd a very large person seating next to me. He should have been made to buy 2 seats. Very uncomfortable for such a long flight."

Pros: "Quick boarding and on time departure and arrival."

Pros: "flight was fairly empty, so very comfortable seating as nearby seats were not occupied."

Cons: "everything was fine -- now the departure and connection to another flight was NOT NEARLY AS SMOOTH !!"

Pros: "food"

Pros: "The flight was one time for departure and arrival"

Pros: "nothing. there is no responsibility from voyama towards clients services"

Cons: "every thing"

Cons: "Seating too tight and close three people sit there arm on each other because no room similarly distance between row is also close food tray falls over"

Pros: "Crew exceptionally nice"

Cons: "Can’t turn off the screen"

Pros: "Short trip"

Cons: "No coffee"

Pros: "Nothing"

Cons: "Bag did t arrive no one to talk to horrible service no home delivery I have to keep going back to airport and talk to stupid young guys who talk too much and do nothing"

Pros: "The flight the plane the staff on plane the food the entertainment"

Cons: "waiting lines to get into the gates and passport checks for departure. it was too long and mis-leading since the machines were not working eventually had to go to a manual check (not machine) and almost missed the flight. It's bad management of the Ben Gurion Airport."

Cons: "On counter, some workers were not nice"

Pros: "Had a great seat"

Cons: "They didn’t offer basic beverages"

Cons: "It is time to change the food! the food is so bad . I get the filling that they don't care' just like that!"

Pros: "On time"

Cons: "No entertainment"

Pros: "Quick, simple flight arriving 7 minutes early."

Cons: "About 12-15 minutes late boarding with no explanation or announcement. Food & entertainment should NOT be rated on such a short flight."

Pros: "Nothing"

Cons: "Bad service bad attitude"

Pros: "The seat room, friendly staff"

Cons: "3 hour delay... not Jordanians fault (fog)"

Pros: "No thing"

Cons: "The staff"

Cons: "Informed by email at 9.30 the previous evening that flight was delayed for 3 hours. Delayed at airport for a further hour. There was no explanation or apology. This must have caused major problems for passengers with f;light connections and for the many who had to get up and go to work the next day."

Cons: "I missed my flight"

Cons: "I actually didn't fly QR. My RJ light from TLV to AMM was delayed by approx 2 hours. I asked to be taken off the flight in order to fly the day after from TLV to LCA and take QR. However the RJ gate agents explained that there are over 40 people on the flight that need to take the QR from AMM and that the ties between RJ and QR are very strong and the QR flight will wait the necessary 15 minutes. However, as we landed in AMM we saw the QR aircraft push back 5 minutes earlier than the scheduled departure. We got stuck in AMM and the RJ people were nice but totally inefficient and claimed that they were limited by their corporate procedures. I asked to be put on an Etihad flight that was scheduled to leave 2 hours later and that would put me at the end of the day in MAA (my destination) around 2.5 hours later which was acceptable in my eyes. The transfer desk agent said he is going to arrange it, disappeared for 45 minutes and then came and told me this is already too late for Etihad (it was not) and anyway they cannot let me take Etihad since they are not a part of "One World". I argued a bit and he said ok went to teh back office and disappeared for another 20 minutes. at that point he came and told me that all is taken care of and here is my new flight and proceeded to show me an itinerary which took me through BKK to MAA but the AMM-BKK flight will leave only at 0130 at night (this was around 1430) and get to BKK in the afternoon tomorrow. Then I will have to wait in the airport another 8-9 hours to fly to MAA. hence 2 nights without sleep staying at airports. BTW, I was the only Business/first passenger but this did not confer on me any special treatment. I refused to take this route and at the end asked them only to get me back to TLV and there I will change the whole route and go tomorrow on QR from LCA. I had to wait at AMM airport until 2100 and only now - 2300 - reached home which I left at 0600 this morning. BTW, i don't think that they restored my ticket to its original form (which was a full QR ticket covering also the RJ and Pegasus flights. but I was too tired to argue. I will postpone my trip by one more day and change the route to avoid another debacle like this one. Also, I chatted with the QR people in Amman, and ithey claim that they were not told that the RJ from TLV had 40 passengers connecting through them. This is the absolute opposite of what the RJ people claimed. Last, all his is without even mentioning the issues this delay caused since I have people who came specifically for this, waiting for me in MAA and God only knows when I will manage to get there and whether or not they will wait for me. Guys, you have to do something about this. I am quite a regular flyer and this is the worst experience I had."

Pros: "Fast check in, Comfort seats"

Pros: "Left on time. Probably overpriced for the length of the flight. Baggage was out promptly."

Pros: "We left early and arrived early. Seats were more spacious than I expected for economy class. It was a short flight so there was no food service, just orange juice."

Cons: "When My luggage was searched at the gate of armman before fly back to Chicago, my camera was taken away by security person, he never returned to me. I only found out when I got home."

Pros: "All"

Cons: "I'll was good"

Pros: "It’s a 25 minute flight. It’s all good. :)"

Cons: "I pre ordered a kosher meal. It was said to me that someone miscalculated and there were not enough kosher meals. I was left hungry and starved on such a long flight."

Pros: "Very short, only a half hour flight"

Cons: "nothing not to like"

Pros: "All new"

Cons: "Extensive security. Warm plane. No charging outlets."

Pros: "The Dreamliner is the best plane I’ve ever boarded, it was used for this short flight."

Cons: "Could not check in online, had to get the boarding pass at the airport."

Pros: "Great service"

Pros: "Modern aircraft"

Cons: "Food is terrible Service is marginal They serve a mediocre meal right after takeoff then you don't see them again until right before landing with a dry snack"

Pros: "Good service, leaving on time"

Cons: "Nothing"

Pros: "Loved all of the kind smiling faces on all of the flight attendants"

Pros: "Nothing."

Cons: "Terrible ground staff. Constant change in flight schedules. No support on codeshares. No on ground help for canceled flights. No ability to print all the boarding passes. terrible connection options. Will avoid flying them ever again if possible."

Pros: "Quick and easy boarding process, nice person at check-in counter"

Cons: "I used the restroom in the plane before takeoff and the it was absolutely filthy. It was clear it did not receive any attention between flights. I was sitting in the emergency exit row and, during takeoff, the plane made a horrible, howling/whining noise that I've never heard before. Everyone was looking around and fearful. I fly often and this was the kind of noise when you wonder "is this where it all ends?" Not sure if it was the engine just outside or the emergency exit not being fully sealed but it was the first time in a long time that I've been fearful on a plane."

Pros: "Everything overall was really good. The crew was helpful and very kind. The food was okay. The chairs were comfortable."

Cons: "The TVs and headphone jacks hardly worked."

The plane never seemed to cool off. Idk if AC wasn’t working. It was warm most of the flight. Other than that it was a good experience.

Nice flight

Flight was on time but seat was very uncomfortable.

Overall, no major problems and all employees were great. The gate area was not large enough for the passengers, so people congregated in the walkway or sat in a different area, which is slightly burdensome because you can’t hear announcements elsewhere. But this is an airport not airline issue and nothing in the short term could address it.

Missed our connection due to delayed. Ended up with a replacement flight with connections getting us in really late and annoying..

I will be very glad when this mask business is over.

Pros: "The flight crew were very nice. I needed help boarding and departing, and they were there every step of the way."

Cons: "Not very much room, no alcoholic drinks available, couldn’t connect to WiFi for inflight movie."

Pros: "The pilot was hilarious and his jokes really helped calm the situation when there was crazy turbulence"

Cons: "My one hour layover turned into a 4 hour past 2AM arrival time."

Cons: "No beverages available to even purchase ! Ridiculous!"

Pros: "Smooth flight, great service onboard"

Cons: "Your seats are too small, but we know the airline industry is not gonna do anything about it."

Pros: "Crew!"

Cons: "Food availability."

Pros: "Yes"

Cons: "Everything was fine"

Pros: "Responsive and helpful crew. Comfortable seating."

Cons: "More snacks; maybe coffee or a second round of refreshments. Not much, really; it was a great experience under the circumstances."

Cons: "Left very late with very poor communications that kept changing as well as the gate info!"

Pros: "Left on time"

Cons: "Customer service was bad"

Pros: "The flight was shorter than we expected! And after a long flight that was most appreciated."

Cons: "Ticket agents were horrible at FAY. Worst I've seen."

Pros: "plane had wifi"

Cons: "multiple gate changes multiple delays boarded and then sat on the plane never pushing back from gate"

Pros: "Thank God for the entertainment options in this flight since it is so long... seats recline a bit but the leg room is a bit small, so by the end everything hurts anyway. Had a nice dinner and several snacks. Not too bad. The crew was pretty friendly. I have no complaints at all about AA."

Pros: "Quick boarding and on time! Speedy and efficient"

Cons: "Long delays"

Pros: "The flight crew was nice. They kept us well hydrated."

Cons: "I expected more from the in-flight entertainment on a 6 hour flight. If I had known I would have brought my own tablet and watched the free in-flight movies that were offered via free Wi-Fi."

Cons: "did not get my requested wheel chair service."

Pros: "All good, on time, crew was pleasant!"

Cons: "All good"

Pros: "Flight depart on time, with possible 5 minute delay. No problem at all."

Pros: "Paid extra for more legroom"

Cons: "No Free WiFi"

Pros: "Personalities...loved their job. Great to talk to."

Cons: "Bosrdunf staff at DCA. No communication in crowded area"

Pros: "Flight on time ."

Cons: "Beyond pritzzels pls have other snack varieties"

Pros: "Gate attendant kept us informed frequently as to the status of the flight"

Cons: "Rudeness/snappiness of the stewardesses"

Cons: "I did not like that the airline would not give a seat on an earlier flight so that I would not have to spend so many hours in the Chicago O'Hare airport. I did not like that the airport only allowed me thirty minutes of access to the internet. As a result, I could not work while I had to wait for my flight. Finally, I did not like that the airline lost or delayed my bag."

Cons: "Flight was 1.5 hours delayed with another 1 hour delay on the tarmac"

Pros: "Boarding and debar king was quick."

Cons: "Attendant was surly, no coffee, no continental breakfast as indicated on the reservation. Very disappointed with in-flight service."

Pros: "No fees for carryon, like Republic charged on the way out"

Cons: "NO seats available on booking, without paying extra. Never could sit together, even though booked together. Greedy but stupid."

Pros: "On time departures. Friendly crew."

Cons: "Nothing"

Pros: "Long wait for take off. Everything else was great."

Pros: "We had a wonderful flight experience. Smooth take off and landing. The in flight service was impeccable! Will definitely be flying American Airlines again."

Pros: "Except for comments under what I didn't like. AA experience was O.K."

Cons: "The restrooms needed cleaned better. Big airplane lots of people, needs cleaned before, during, and after. Had to pay for the Wi-Fi, that I used for 30 min, basically for E-Mail."

Cons: "Because it was a day later!!!"

Pros: "Much better than the trip to chicago"

Cons: "Had to wait on the crew Short fight rushed service"

Cons: "The departure was delayed. And is unbelievable you are charging baggage"

Pros: "The price is competitive. On boarding was ontime. Though the flight was redirected to Omaha due to bad weather in Kansas City, it was only an hour late than the scheduled arrival to Kansas City."

Cons: "The WiFi was not as expected. In flight entertainment is null. Snack would have been better."

Pros: "Nice plane when we finally boarded it. Crew was very professional."

Cons: "Endless advisories, the official explanation of the flight delay and estimated departure was constantly in flux."

Pros: "very good no problems.."

Cons: "all good thanks much"

Pros: "Flight was delayed but boarding at DCA was very efficient and quick"

Cons: "Flight attendants seemed bothered by something and weren't very nice. They looked/seemed tired. Cabin lights were on the whole time for a ~3 hour flight which began at 830pm."

Pros: "Crew very courteous"

Cons: "Flight was delayed 2 hours. I couldn't run my business that way!"

Done entertainment for the kids. It's a long journey. Bring back your old aeroplane food, I used to love your cooked breakfast when we had a really early start.

Overall everything was smooth and pleasant

Canceled my trip never flew. They were rude and uninformed. Caused me grief wanting another covid test even though I had one plus I am vaccinated. No excuse. They should have had a test station by their ticketing counter. Had to hunt for transportation which was very difficult since it was 10 pm. Rented car for 350 to get home. I would think twice before booking through Kayak and with BA. kayak should have had more assistance and not just sell the ticket. Both receive an F .

Cons: "The pancake was not cooked enough couldn’t eat it"

Cons: "Boarding process.."

Pros: "Flight was not full, so despite a sub-par Business Class product the flight was very pleasant with empty seats all around"

Cons: "On line check-in/seat selection was a disaster"

Pros: "The flight was relatively on time and the crew was nice"

Cons: "The food was not the British Airways high quality"

Pros: "great crew great seats great entertainment great pilots great food and the greatest airline in the world"

Cons: "free wifi"

Pros: "Our flight attendant was awesome. Very friendly and attentive."

Cons: "The cabin temperature was cold and the flight was delayed by over an hour."

Cons: "On time departure"

Pros: "-"

Cons: "Entertainment didn’t work, big delay broken seat"

Pros: "Great !"

Cons: "Kosher meal a bit hard to open"

Cons: "The entertainment system wasnt working on the first flight, and had poor content on the second flight."

Pros: "Nothing particularly"

Cons: "Food was awful"

Cons: "It’s hard to get used to not having seat-back entertainment when you’ve had it the rest of the trip!"

Pros: "Nothing. Flight attendant throws the tray of food all over me. Never apologize Worst flight ever I'm a Gold Frequent Flyer. No more!!! Good Bye British Airways Hello Cathay Pacific!"

Cons: "way too crowded"

Pros: "we buy the tickets from kayak and reconfirmed with British Airways is that we allowed to have one suitcase of 23 kilo checked in for each person . would get to their products and we paid 180 US dollars for the read suitcases we have . I didn’t mention kayak to give me the 180 us dollar back"

Cons: "we buy the tickets from kayak and reconfirmed with British Airways is that we allowed to have one suitcase of 23 kilo checked in for each person . would get to their products and we paid 180 US dollars for the read suitcases we have . I didn’t mention kayak to give me the 180 us dollar back"

Pros: "The attitude of crew long ques for toilet"

Cons: "Long queues for toilet"

Pros: "The crew was kind and professional, cosy seats with enough place for the legs... Good content in entertainment system."

Pros: "Flavor was fine"

Cons: "Out of 6 special vegetarian meals provided on 4 recent flights, all were pasta. One main meal of pasta even had A SIDE of pasta salad."

Cons: "the food"

Pros: "Not much. Even magazines were not available for 2 last raws."

Cons: "Even magazines were not available for 2 last raws"

Pros: "Service, clean restroom, courtesy of crew members"

Pros: "Service"

Cons: "None"

Pros: "Nothing really was good or stood out in a positive way."

Cons: "Horrible lie flat seats with absolutely no stowage room. Seats are super cramped with 8 in a row you feel like being transported in a cattle car. Crew was most decidedly unfriendly. We were boarded on time despite the fact BA knew the flight was delayed and sat at the gate for an hour. Food was equivalent to hospital food. U must be crazy to fly business in BA. Never again."

Cons: "No breakfast on out bound leg"

Cons: "Don’t do it!! Totally disorganized airline with uncomfortable seats."

Pros: "The crew were very helpful"

Pros: "My upgrade."

Cons: "That I needed to be searched again before boarding the plane. The long layover."

Pros: "On time"

Cons: "Paid for bulkhead seat and was not given a bulkhead seat."

Pros: "Good and crew were fine"

Cons: "Seats were too close, not comfortable"

Cons: "the flight delayed a lot and i missed my connection flight as a result"

Pros: "World Traveler Plus on BA is not as good as premium economy on other airlines."

Cons: "Check in. Too many people checking in and too few BA employees to handle crowd. Severely understaffed."

Pros: "Most things"

Cons: "The airplane was shaking all the flight"

Pros: "The new flight procedures informational film at the beginning of the flight (BA/Comic Relief)"

Cons: "The flight was to Heathrow which was not prepared to accept us at all. We waited 45 minutes in passport control. I expect BA to make sure the port of destination is prepared to receive its passengers"

Cons: "I booked a regular flight and at the end the system or dont know how, booked me PLUS ECONOMY, when I wanted to change my ticket date, it was so expensive and almost no dates were available. Also, you didnt give me chance to downgrade in order to change the dates more easily. I always fly through BA and I love the easy it is to change dates, but this time you disappointed me. I usualy choose BA because its easy and non expensive to change dates in my flight but now I may be open to book with other airlines."

Pros: "The flight was smooth from boarding to landing early at Heathrow."

Cons: "It was a fully booked flight, which means the person next to you tends to overflow into your seat"

Cons: "I paid 100$ because I had to cancel my request. It was a technical error of your reservation system which unexpectedly changed my return from the 5th of November to the 6th of November. The fine was unfair and you're required to refund me."

Pros: "The staff were some of the friendliest I have encountered in recent traveling experiences. They were very attentive to every passenger."

Cons: "We only paid for economy seats, and unfortunately, it's hard to expect much more than what we got. The friendly service made up for the lack of comfort these seats provide."

Pros: "Upgraded to world traveler plus was way more comfortable. The flight crew were so so nice and helpful. I am handicapped and they just couldn't do enough to make me comfortable."

Cons: "They the seats I reserved months ago were changed."

Pros: "I loved the on-demand entertainment which starts as soon as you board the plane and continues all the way into landing / taxing to the gate."

Cons: "The system would not allow me to check-in / get my boarding passes 24 hrs prior to barding, which basically left me with a middle seat all the way to Seattle. I considered this a terrible process and didn't get a good explanation why I was blocked from doing my check-in online."

Cons: "No food selection. No vegan meal that i ordered for my daughter."

Pros: "Most everything"

Cons: "Seat choice"

Cons: "BA cancelled the flight, did not reroute us, provided a phone number for tel aviv (closed for the weekend). Terrible customer service. And our ticket was bought thru vayama who also did not bother to help us. Bad bad customer service for BA."

Pros: "entertainment"

Cons: "boarding with bus instead of sleeve"

Pros: "Security staff was rude in England and our suitcases was lost And they did not even let us know"

Pros: "The crew was very efficient"

Cons: "The was really bad."

Cons: "I received no information from British Airways! Luckily someone saw that all flights on BA had been canceled. This is the second time this has happened with British Airways. They have zero customer service and terrible communication."

Pros: "the over seas flight was fine... once we got on board"

Cons: "The desk does not open until two hours before your flight. Our flight was canceled, 10 minuets before boarding .... with no recourse we were booked on the next day. It took the airline 3 hours after the cancelation to get out luggage back. When we finally got out, the next day, our flight was delayed and we almost missed our connection. Every one who was trying to make the same connection said that every time they fly Air Canada they are always running. We needed up being the last ones on the plane.... they gave away our seats so we were separated for 12 hours. And shoved into corners!!! Our bags made it two days late."

Cons: "Connecting flight in Toronto late 4 HOURS!!!!! There is no excuse for such delay. Another plane should have been made available for the flight."

Pros: "Flight wasn't crowded and it was a quiet flight."

Cons: "Flight was delayed an hour, but baggage arrived fine."

Pros: "Every thing"

Cons: "Everything was amazing"

Pros: "Everything went well, the crew was great."

Cons: "Not enough leg room Cramped seating area in coach"

Pros: "Crew we're very accommodating and friendly."

Cons: "Seats extremely narrow and back support non-existent."

Pros: "Overall, flights were ok"

Cons: "4 hour delay in Toronto for our connection."

Pros: "nice food great crew"

Cons: "the washrooms need more cleaning during this long flight messy boarding"

Pros: "great crew."

Cons: "no wifi on a transatlantic 12 hour flight!!!!"

Cons: "They feel like seats for budget flights."

Pros: "Really liked I have space for my legs."

Cons: "the food"

Pros: "Good legroom and entertainment options, on time. Enjoyable overall."

Cons: "Food showed British heritage -- stodgy, boring, overcooked. The bathrooms were dirty and out of supplies after a while."

Pros: "You fly a beautiful plane, the Boeing 787. Excellent entertainment, more comfortable seats, and just about everything on this plain was upgraded. It is a case study of how to do things right. The most impactful for me was air humidity. It was refreshing to fly and not feel like I've been in the Sahara desert at high noon. So, your starting point is really high, but you really need to look at your service."

Cons: "our flight was 40 minutes late in departing TLV. My connection in Toronto then was changed to a later flight, which was then delayed too by 50 minutes. all in all a 14 hour flight with connection ended up being close to 18 hours. My biggest two complaints about the flight itself is the food & the toilets. Your meals are the worst I've had in a major airline, and you should not serve customer frozen of close to frozen bread or sandwiches. If you are serving rolls, sandwiches or pitas, or bagels heat them up first. El-Al has been doing it for decades, go look at how they do it. But besides the bread/sandwiches issue, your meals are a really bad version of frozen supermarket meals. Just terrible all round. The other complaint is the bathroom. It was not cleaned frequently enough."

Pros: "Tel Aviv security is confusing and time consuming but Air Canada helps you make it through. Flight is on a comfortable new airplane with gray movie selection. Two full meals and a snack provided."

Cons: "Everything Luggage no come on time This is the worst company"

Pros: "The flight was relatively empty, so there was a lot of room. Had it been full, I'm not sure I would have rated comfort so highly."

Pros: "Very accommodating with my seating requests; very kind staff and nice new plane"

Cons: "Got delayed in toronto for 24 hrs and there was a lot of waiting and disorganization"

Pros: "Very friendly flight attendants. Great food!"

Pros: "Food good Choice of movies pretty good"

Cons: "Suitcase damaged No one in Detroit to process claim Amount of wine offered was somewhat meager for such a long flight"

Cons: "AIr Canada lost my luggage and the return flight was late"

Pros: "My flight to Toronto arrived late which meant there would be no way for me to catch my connecting flight to North Carolina. An Airline rep was already waiting for me out of the terminal, with tickets for a new flight the next morning, a ticket for one night at one of the airport hotels(dinner included) and meal vouchers for the airport. This would have never happened with any US based airline."

Cons: "There was no information for the new rules of eTA and I've lost my flight from Tel Aviv to Toronto to my friends baby's baptism. Shame!"

Cons: "Not on time. I missed my connecting flight"

Cons: "With an hour delay out of Paris due to waiting for missing aircraft flight documents to be completed and delivered to the airplane on the holding ramp, we ended up arriving in Toronto an hour late. With only an original connection time of 90 minutes, it was not possible for me to make it thru Canadian and US customs to the connection gate. I was to learn that no other connection to a Kansas City was available until much later in the afternoon / early evening. As a result, I ended up arriving in Kansas City 6 (six) hours later than originally scheduled, three quarters of the time it took to travel from Paris to Toronto. To say the least , I was not at all thrilled having lost that time."

Cons: "The flight was delayed about an hour and a half, only after some time at the gate they explained it on the mic.I had a connection flight, and before landing they mentioned there will be agents helping those with upcoming connections to catch them up due to the delay, but those people just pointed me in the general direction of the gates. I had to ran all over the airport, confused after the terrible long flight, and since it was my first time there. I made it at the last second, they changed my seat without my permission and didn't have enough room for my bag so I had to check it. The general attitude of the crew was reluctant at best.The food was mediocre, like what you would have gotten in a flight 10 years ago, and they gave beef to people who asked for chicken. I wanted to be more cool about it, but it was a terrible flight in every Aspect, and I never even got an apology or a follow up."

Cons: "I did not like aircanada changed my sit without asking me.I did not like delays."

Pros: "Food need to improve it's no taste and stank of meat"

Pros: "Boarding and crew were very good."

Cons: "Air Canada Legs were excellent, but Rouge Sucks!"

Pros: "Staff was super nice to my surprise."

Cons: "Flight was late."

Pros: "The attendants were helpful The food was good"

Pros: "New aircraft 787. Direct flight from Israel to Canada, no layover in Europe. That was nice. The crew was very friendly and helpful. The worst part was the airport in Toronto. Very confusing to get around in. And having to fill out custom papers for Canada when I wasn't staying in Canada or leaving the airport. Didn't like that. But the service of Air Canada makes up for the airport, I would use their service again."

Pros: "There are a variety of entertainments section."

Cons: "During transfering from air canada to delta an employee failed to transfer all my baggage. As a result I couldn't get one of my baggage yet. Moreover there was no reservation made for me and I missed the flight since I lost the time by going back and forth to Delta and Air Canada offices to fix the problem. As a result I spent the night at Detroit and take the next day flight."

Pros: "the mounties rock, seriously"

Cons: "Flight was pleasant and food was good. I ordered veggie meal and for some reason I didn't get it on the second meal."

Cons: "Food was bad,"

Pros: "The staff was very friendly and extremely accommodating."

Cons: "There could have been a bit more on the entertainment selection side."

Pros: "I loved the 787 with the mood lighting and humidified air. The flight attendants were very nice and attentive. I loved the warm towels after take off and before landing!!!"

Cons: "I had a 4 hour layover in Toronto. Could have done with a much shorter layover. A Dr. Pepper as a soda selection would be nice but not essential."

Pros: "The crew was nice and friendly"

Cons: "The seats are too tight"

Pros: "The crew was polite and friendly."

Cons: "The food was not good"

Pros: "Great customer service great people"

Cons: "Having to pay for changing return date. You should have an open ticket option for extended stays"

Pros: "The 787 is avery comfortable airlplane."

Pros: "The flight attendants were very professional and caring"

Cons: "My vegetarian food choice did not transfer from my United Airlines profile"

Pros: "Air Canada is a first rate provider. Their air rates are better than most other airlines, and the value for the money is exceptional."

Cons: "The plane was SO, SO COLD. The entire plane of people were miserable. I literally shivered all the way from Toronto to Istanbul, huddled next to the stranger next to me, who was also freezing. It was unreal how cold it was. People kept asking the staff to turn the A/C down, to no avail. I couldn't wait to get off that flight."

Pros: "Love the new planes and choose aircanada for all my Tel Aviv flight because of this"

Cons: "Food is terrible and it's always very cold. Near the end of the flight the A/C started leaking water from the ceiling."

Pros: "The crew appeared overworked and understaffed. I feel that there should have been at least 2 to 4 more to help with the large number of passengers on the plane. It appeared to be more than full and perhaps extra seating was added."

Cons: "The plane was overcrowded. Seating was extremely uncomfortable and much too narrow. I am a relatively thin person but the person to my right was large and kept on pushing into me during the entire flight. Plus it took us over an hour and 30 minutes before we left the airport because we had to wait until the entire plane off boarded before a wheelchair could be brought for my wife. After the wheelchair was brought and we picked up our luggage, (2 bags), which by the way were the last 2 on the carousel, there was only one line through customs for people with special needs. By the time we left the airport I spent at least 45 minutes trying to find the cab which had been sent from Rochester, NY to pick us up and when I finally found him he wasn't allowed to stop in the taxi lane to pick us up in the taxi lane because he wasn't an authorized cab in spite of the fact that I told the security person that my wife was in a wheelchair and the weather was close to 0 degrees celsus and it was snowing."

Pros: "Friendly staff, not as crowded as most airlines"

Cons: "There was nothing to not like -- they might need a few more rest rooms for the coach classes"

Pros: "This was my first Air Canada flight, and I was beyond impressed with the service overall. The plane was extremely nice and very spacious. The flight crew was very attentive and helpful, and had great attitudes. I had trouble with my entertainment screen early on, and a flight attendant went out of her way to reset and make sure it was working for me. The 12 hour flights both ways were comfortable and enjoyable."

Cons: "I honestly can't say anything negative about this experience!"

Homeopathic Medicine for Hiatal Hernia Problem

A hiatal hernia occurs when part of your stomach pushes upward through your diaphragm. Your diaphragm normally has a small opening (hiatus) through which your food tube (esophagus) passes on its way to connect to your stomach. The stomach can push up through this opening and cause a hiatal hernia.

Hiatus Hernia Treatment in Homeopathy

In most cases, a small hiatal hernia doesn't cause problems, and you may never know you have a hiatal hernia unless your doctor discovers it when checking for another condition. But a large hiatal hernia can allow food and acid to back up into your esophagus, leading to heartburn. Self-care measures or homeopathic medications can usually relieve these symptoms of Hiatal Hernia, although a very large hiatal hernia sometimes requires surgery.

Causes of Hiatal Hernia 

A hiatal hernia occurs when weakened muscle tissue allows your stomach to bulge up through your diaphragm. It's not always clear why this happens, but pressure on your stomach and age-related changes in your diaphragm may contribute to the formation of a hiatal hernia.

How Does a Hiatal Hernia Form

Your diaphragm is a large, dome-shaped muscle that separates your chest cavity from your abdomen. Normally, your esophagus passes into your stomach through an opening in the diaphragm called the hiatus.

Hiatal hernias occur when the muscle tissue surrounding this opening becomes weak, and the upper part of your stomach bulges up through the diaphragm into your chest cavity. Possible causes of hiatal hernia:

  • Injury to the area
  • Being born with an unusually large hiatus
  • Persistent and intense pressure on the surrounding muscles, such as when coughing, vomiting or straining during a bowel movement, or while lifting heavy objects

Symptoms of Hiatal Hernia in Stomach

Most small Hiatal hernias cause no signs or symptoms. However, larger Hiatal hernias can cause signs and symptoms such as:

Risk Factors of Hiatal Hernia

Hiatal hernia is most common in people who are:

Homeopathic Medicine for Hiatus Hernia

Homeopathy today is a rapidly growing system and is being practiced all over the world. Its strength lies in its evident effectiveness as it takes a holistic approach towards the sick individual through the promotion of inner balance at mental, emotional, spiritual, and physical levels.

Effective medicines are available in homeopathy for hiatus hernia problem, but the selection depends upon the individuality of the patient, considering the mental and physical symptoms.

  1. Calcarea carbonicum 200 - Calcarea carb is an excellent homeopathic remedy for hiatus hernia, and it helps for strengthening the relaxed weak muscles. Calcarea carb is suitable for fat, flabby obese persons who perspire profusely. Heartburn and loud belching. Frequent sour belching, sour vomiting of curdled milk. Cramps in the stomach, worse pressure, cold water. Swelling over a pit of the stomach like a saucer turned bottom up. Pain in the epigastric region to touch. Aggravation while eating. There is a special craving for indigestible things like chalk, coal, pencils, etc.
  2. Robinia 3x - Robinia is one of the effective homeopathic medicines for hiatus hernia with heartburn and acidity of the stomach. S our stomach. Great acidity of the stomach at night on lying down. Nausea with sour belching. Profuse vomiting of intensely sour fluid. Heavy, aching, dullness in the stomach. Very severe, sharp pains in the stomach all day and night. Great distension of stomach and bowels
  3. Phosphorus 200 - Phosphorus is another homeopathic remedy for hiatus hernia with a sour taste and sour eructations after every meal. Belching large quantities of wind after eating. Throws up foods by the mouthfuls. Water is thrown up as soon as it gets warm in the stomach. Pain in stomach, relieved by cold foods, ices etc.
  4. Natrum Phos 30 - Natrum Phos is prescribed where heartburn and sour belching are present. Belchings after eating. Spits mouthfuls of food. Vomiting of sour cheesy masses, especially in the morning. Heaviness and pressure in the epigastrium.
  5. Carbo vegetabilis 3x - Carbo vegetabilis is excellent hiatus hernia homeopathic medicine with difficulty in breathing. Contractive pain extending to chest with distension of abdomen. Waterbrash, asthmatic breathing from flatulence. Belching after eating and drinking, temporary relief from belching. Eating the simplest kind of food causes sour belching. Belching, heaviness, fullness and sleepiness, tense fro flatulence with pain, worse lying down. The epigastric region is very sensitive.
  6. Abies nigra 30 - Abies nigra is an effective homeopathy remedy for hiatus hernia with a sensation as if a hard-boiled egg had lodged in the cardiac end of the stomach. A distressing and constriction just above the pit of the stomach, as if everything were knotted up. Pain in the stomach immediately after eating. Waterbrash with choked feeling in the throat.
  7. Nux vomica 30 - Nux vomica is the best homeopathic remedy for hiatus hernia with great sensitivity in the area of the stomach. Complaints after taking highly spicy food, coffee, and alcoholic drinks. Waterbrash, sour and bitter risings, nausea, and vomiting. Indigestion with hiatus hernia. The patient is highly irritable and sensitive to noise and light.
  8. Lycopodium clavatum 200 - Lycopodium is indicated for hiatus hernia with great weakness of digestion with much bloating, heartburn, and indigestion after takin flatulent food, cabbage, beans, oysters and onions. Belchings rise only to the pharynx. The patient prefers hot food and hot drinks. Craving for sweets.
  9. Pulsatilla nigricans 30 - Pulsatilla is effective homeopathic remedies for hiatal hernia where the complaints arise after taking fatty, rich foods. The stomach disordered and feels heavy. Waterbrash with a foul taste in the morning.

Update From Lybrate: To keep your Gut Health on track and to avoid constipation and gastric troubles. We suggest you to buy Gut Care Products available on Lybrate at affordable prices.

In case you have a concern or query you can always consult a specialist & get answers to your questions!
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    Mapping Actuarial Criteria for Parkinson’s Disease-Mild Cognitive Impairment onto Data-Driven Cognitive Phenotypes

    Logo of brainsci

    Lauren E. Kenney,1,2,*Adrianna M. Ratajska,1,2Francesca V. Lopez,1,2Catherine C. Price,1Melissa J. Armstrong,2,3 and Dawn Bowers1,2,3

    Melissa J. Armstrong

    2Norman Fixel Institute of Neurological Diseases, University of Florida, Gainesville, FL 32603, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32603, USA

    Find articles by Melissa J. Armstrong

    Dawn Bowers

    1Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32603, USA; [email protected] (A.M.R.); [email protected] (F.V.L.); [email protected] (C.C.P.); [email protected] (D.B.)

    2Norman Fixel Institute of Neurological Diseases, University of Florida, Gainesville, FL 32603, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32603, USA

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    Pierluigi Zoccolotti, Academic Editor, Dona E. Locke, Academic Editor, and Andrea Loftus, Academic Editor

    Author informationArticle notesCopyright and License informationDisclaimer

    1Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32603, USA; [email protected] (A.M.R.); [email protected] (F.V.L.); [email protected] (C.C.P.); [email protected] (D.B.)

    2Norman Fixel Institute of Neurological Diseases, University of Florida, Gainesville, FL 32603, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32603, USA

    *Correspondence: [email protected]

    Received 2021 Nov 11; Accepted 2021 Dec 22.

    Data Availability Statement

    The datasets presented in this article are not publicly available because an inquiring party must submit a request to the UF INFORM database committee at the Norman Fixel Institute of Neurologic Diseases, and this request must be approved by the UF IRB. Requests to access the datasets should be directed to “Chuck Jacobson, [email protected]”.

    Abstract

    Prevalence rates for mild cognitive impairment in Parkinson’s disease (PD-MCI) remain variable, obscuring the diagnosis’ predictive utility of greater dementia risk. A primary factor of this variability is inconsistent operationalization of normative cutoffs for cognitive impairment. We aimed to determine which cutoff was optimal for classifying individuals as PD-MCI by comparing classifications against data-driven PD cognitive phenotypes. Participants with idiopathic PD (n = 494; mean age 64.7 ± 9) completed comprehensive neuropsychological testing. Cluster analyses (K-means, Hierarchical) identified cognitive phenotypes using domain-specific composites. PD-MCI criteria were assessed using separate cutoffs (−1, −1.5, −2 SD) on ≥2 tests in a domain. Cutoffs were compared using PD-MCI prevalence rates, MCI subtype frequencies (single/multi-domain, executive function (EF)/non-EF impairment), and validity against the cluster-derived cognitive phenotypes (using chi-square tests/binary logistic regressions). Cluster analyses resulted in similar three-cluster solutions: Cognitively Average (n = 154), Low EF (n = 227), and Prominent EF/Memory Impairment (n = 113). The −1.5 SD cutoff produced the best model of cluster membership (PD-MCI classification accuracy = 87.9%) and resulted in the best alignment between PD-MCI classification and the empirical cognitive profile containing impairments associated with greater dementia risk. Similar to previous Alzheimer’s work, these findings highlight the utility of comparing empirical and actuarial approaches to establish concurrent validity of cognitive impairment in PD.

    Keywords: Parkinson’s disease, mild cognitive impairment, movement disorders, cluster analysis, prevalence

    1. Introduction

    The experience of Parkinson’s disease (PD) encompasses not only the prototypical motor symptoms but also a plethora of non-motor symptoms including cognitive changes. Past research estimates that approximately 40% of people with PD have mild cognitive impairment (PD-MCI) at any given time, and up to 80% of individuals with PD will develop dementia after living with the disease for 15–20 years [1,2]. However, the trajectory of cognitive changes can differ among individuals with clear diagnoses of idiopathic PD—with some declining more rapidly than others [3]. Therefore, while the endpoint of the trajectory is known for many individuals with PD, the question remains who is most at risk for a more rapid transition to Parkinson’s disease dementia (PDD).

    Two lines of research aim to answer this question. Some studies take an empirical approach by statistically examining neuropsychological data to see what patterns of cognitive performance arise. This is often done via use of cluster analytic techniques, resulting in distinct clusters or cognitive phenotypes. Others take an a priori classification approach, meaning that mild cognitive impairment (MCI) is designated by specific impairment criteria, which are then used to identify patterns of deficits across cognitive tests or domains. One way of doing this is via “actuarial classification criteria”, defined as using objective, pre-established numerical definitions of impairment, rather than a consensus diagnosis or clinical judgment. Both empirical (cluster analytic) and actuarial/clinical theoretical classification approaches aim to characterize distinct cognitive profiles in PD-with the hope of subsequently determining if certain cognitive profiles or subtypes connote greater risk of developing PDD at faster rates.

    Recently, comparison of the predictive utility of these two types of approaches (cluster analysis vs. a priori classification) has gained traction among researchers in the MCI-Alzheimer’s disease (AD) literature. Indeed, recent studies have found that cognitive phenotypes derived from cluster analyses are more strongly correlated with AD biomarkers and are more strongly linked to dementia progression than traditional a priori classification methods [4,5]. To date, few studies have compared these two approaches in individuals with Parkinson disease or addressed some of the psychometric issues inherent when comparing these approaches to each other [6,7].

    Historically, the cognitive sequelae of Parkinson’s disease have been linked to deficits in executive function (e.g., planning, inhibition, problem solving), processing speed, and working memory and attributed to dopaminergic depletion in fronto-striatal networks [8,9]. Even so, various studies have found less prevalent, yet still pronounced, deficits in other cognitive domains such as memory [10,11], visuospatial skills [12,13], and semantic language function [14]. These varying cognitive sequelae of PD play out in both data-driven and classification approaches. Use of data-driven approaches (e.g., cluster analyses) has resulted in some variability in the patterns of PD cognitive phenotypes across studies. Some reveal phenotypes that primarily differ in the level and breadth of cognitive impairments [15,16,17]. Yet, other studies identify clusters that differ in the “types” of cognitive domains that are impaired [18,19,20]. For example, Crowley and colleagues [21], in a recent cluster analytic study, with prospectively recruited individuals with PD, identified three cognitive phenotypes—those showing low executive function, those with low episodic memory performance, and those with no deficits relative to age matched controls.

    There is also variability in the rules of the road used by various a priori classification approaches for identifying “mild cognitive impairment” in individuals with PD [22]. Most MCI classification approaches differ in terms of stringency of psychometric criteria such as number of cognitive tests used, use of composite scores, and impairment cutoff criteria. In 2012, the Movement Disorders Society (MDS) published consensus criteria for PD-MCI [23]. The Level II “comprehensive” criteria, which requires more extensive neuropsychological testing beyond a cognitive screener, defined impairment as having two or more tests falling 1–2 standard deviations (SD) below the normative mean or demonstrating a relative decline from previous evaluation [23]. While a diagnosis of PD-MCI using the MDS criteria is associated with greater risk of developing PDD [24], even with unified criteria, the prevalence rates of PD-MCI continue to range from 25–65% across studies [25,26]. Such disparate estimates of the portion of individuals with PD-MCI limits this diagnosis’ effectiveness at predicting clinical trajectory to dementia.

    In part, the variability in prevalence of PD-MCI across studies results from methodologic differences (i.e., community vs. clinical sample, sample sizes, which neuropsychological tests that are used). However, beyond that, the operationalization of impairment (e.g., use of −1, −1.5 or −2 SDs) is a critical issue. Moreover, variable use of cutoff criteria relates to the notion of “decline” from a previous level, but this hinges on the assumption that test “norms” are inadequate to capture change in certain demographic sectors. Currently, results remain mixed over which cutoff criteria best identifies who is at greatest risk for impending dementia [8,24,27]. Previous work comparing empirical approaches to a PD-MCI classification, based on a prespecified impairment cutoff (−1.5 SD), found greater portions of PD-MCI participants in the more broadly impaired or amnestic phenotypes [6,7].

    The overall goal of the present study was to address the issue of “cutoff” criteria head on by comparing clinical classification and data-driven approaches in a large clinical sample of idiopathic PD patients without dementia. We specifically wanted to learn which cutoff was optimal for classifying individuals as PD-MCI. This is important as it works towards establishing more consistent prevalence rates of PD-MCI. To achieve this goal, the current study first examined the influence of using different SD impairment criteria on PD-MCI prevalence rates and subtypes. Next, we identified data-driven cognitive phenotypes using cluster analysis in this same clinical sample. Taken together, these two approaches enabled us to determine how well the PD-MCI classifications mapped onto the cluster-derived cognitive phenotypes using each of three common SD impairment cutoffs.

    Based on previous literature [28,29,30,31,32], we predicted that the following empirically based phenotypes would emerge from cluster analyses: normatively average cognition, isolated executive function impairment, and broader cognitive impairment across multiple domains, particularly executive function, memory, and visuospatial. We predicted that a greater proportion of the PD-MCI cases would be represented in the cluster with broad cognitive impairment due to involvement of cortical systems underlying lower memory, visuospatial, and executive performance. Impairments in these domains have previously been shown to put individuals with PD at greater risk of developing PDD [33,34,35]. Finally, we planned to determine which impairment cutoff jointly maximized the model’s sensitivity and specificity and produced the highest classification accuracy.

    2. Materials and Methods

    2.1. Design

    We performed a cross-sectional, observation study by conducting a retrospective chart review of individuals with PD seen at the University of Florida (UF) Health Norman Fixel Institute for Neurological Diseases. Data encompassed participants’ demographics, disease-related characteristics, neuropsychological assessment, and mood/motivation screening measures.

    2.2. Participants

    Participants included a convenience sample of individuals with idiopathic PD from a large IRB-approved prospectively acquired clinical-research database (INFORM) of movement disorders patients seen at the UF Norman Fixel Institute. For the current study, inclusion criteria were: (1) evaluation between 2002 and 2019 and (2) a diagnosis of idiopathic PD made by a fellowship-trained movement disorders specialist based on the UK Parkinson’s Disease Society Brain Bank Diagnostic Criteria. Exclusion criteria entailed (a) any current major psychiatric disturbance (i.e., unmanaged bipolar disorder, schizophrenia, current episode; n = 7); (b) a comorbid essential tremor diagnosis (n = 13); (c) previous brain surgery (e.g., deep brain stimulation, pallidotomy; n = 87); (d) history of epilepsy, stroke, or brain injury with ongoing cognitive sequela (n = 18); (e) missing neuropsychological measures utilized in the study (n = 187); (f) evidence of significant cognitive impairment based on scores below 125 on the Dementia Rating Scale-2 (DRS-2, n = 127) [36], a cutoff which corresponds to ≤10th percentile [37]. After excluding (n = 439) participants from the starting sample (n = 933), this resulted in a final N of 494 participants for the current study.

    2.3. Neuropsychological Measures

    All participants received a comprehensive neuropsychological assessment. The battery consisted of the DRS-2 (as a general index of cognitive impairment) and standard neurocognitive measures in the domains of (1) executive function, (2) verbal delayed memory, (3) language, (4) visuospatial skills, and (5) attention/working memory. Specific tests are shown in Table 1, and cognitive measures are grouped by domain based on theoretical considerations [38,39,40]. Norms for each test were derived from test-specific manuals or previously published norms [41] and then converted to z-scores. Using normative data allowed us to compare performance to that expected in the population and more closely reflected clinical practice. However, this approach did present the limitation that measures were normed based on different samples and did not all adjust for additional demographics, such as education.

    Table 1

    Neuropsychological Tests within Each Cognitive Domain Composite.

    Cognitive DomainTestsRaw Score Used
    Executive FunctioningStroop Test (Interference trial)
    TMT Part B
    Letter Fluency (FAS)
    Total Number of Correct Items
    Completion Time
    Total Number of Words (all 3 trials)
    Verbal Delayed MemoryHVLT-R
    WMS-III Logical Memory
    Delayed Total Recall
    Delayed Total Recall
    LanguageBNT
    Semantic Fluency (Animals) *
    Total Correct Spontaneous Responses
    Total Number of Words
    Visuospatial SkillsBenton JOLO
    Benton FRT
    Total Items Correct
    Total Items Correct
    Attention/Working MemoryWAIS-III Digit Span Forward
    WAIS-III Digit Span Backward
    Total Number of Points
    Total Number of Points

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    For the majority of cognitive measures, less than 6% of the available sample had missing data. Only the measures included in the visuospatial composite contained a greater portion of missing data (Judgment of Line Orientation: 8.08%, Benton Facial Recognition Test 14.41%). However, when analyzing the pattern of missing values for all cognitive measures, Little’s Missing Completely at Random (MCAR) assumption was supported (χ2(304) = 324.61, p = 0.20). Because participants needed at least two measures per domain for PD-MCI classification, listwise exclusion (if missing any neuropsychological data) was implemented.

    2.4. PD-MCI Classification

    We classified participants as cognitively normal or meeting actuarial criteria for PD-MCI using three commonly used impairment cutoffs: liberal (−1 SD), midpoint (−1.5 SD), and conservative (−2 SD). For a cognitive domain to be considered impaired, the normative scores on at least two tests within that domain had to fall below the respective cutoff (i.e., −1, −1.5, −2.0 SD). Having at least one impaired domain led to a classification of PD-MCI. This differs from the MDS criteria which allow PD-MCI to be defined by having one impaired test across two separate domains, with the implication that both of those domains are considered impaired. We took a more psychometrically rigorous approach by requiring two or more tests within the same domain to fall below the respective cutoff to assign a classification of PD-MCI. Indeed, this approach is more predictive of PDD [27], minimizes the possibility that poor performance on a single task is an anomaly, and aligns more closely with widespread clinical practice of defining domain impairment based a pattern of deficits across measures within a domain.

    Participants designated as having PD-MCI were then divided into subtypes based on whether they were impaired on one or multiple cognitive domains and whether executive function (EF) impairment was present or not. Just as the originally proposed MCI subtypes (amnestic/non-amnestic) aimed to distinguish the presence of or absence of the hallmark characteristic of Alzheimer’s disease [54], we focused on the presence or absence of the most common cognitive impairment (i.e., executive function) in PD. Thus, PD-MCI participants were characterized as being one of four subtypes: single-EF (only EF domain impaired), multi-EF (EF plus at least one other domain impaired), single-non-EF (one domain impaired but not EF), and multi-non-EF (more than one domain impaired but not EF).

    2.5. Cluster Analyses

    For each cognitive domain, a composite score was computed by averaging individual z-scores of tests within a domain. The five domain composite scores were then entered into the cluster analyses to distinguish cognitive phenotypes (groups of participants with similar patterns of cognitive performance). For the current manuscript, we refer to these cluster-derived subtypes as “cognitive phenotypes” to distinguish them from the subtypes derived from the PD-MCI classification. While we had an a priori prediction of three clusters, we tried a range of two to four clusters to ensure ideal data fit; several cluster solutions were generated and contrasted before determining the final cluster structure.

    2.6. Other Measures

    At the time of the neuropsychological evaluation, participants completed self-report screening measures to characterize symptoms of depression (Beck Depression Inventory-II (BDI-II)), apathy (Apathy Scale (AS)), and situational and dispositional anxiety (State-Trait Anxiety Inventory (STAI)) [55,56,57]. To gauge motor symptom severity and disease stage progression, ratings from the Unified Parkinson’s Disease Rating Scale (UPDRS, [58]) Part III and the Hoehn and Yahr scale (H&Y, [59]) were obtained by movement disorder neurologists while participants were “on” their dopaminergic medications. These neurologists also characterized their motor subtype (tremor predominant, akinetic-rigid, or postural instability and gait difficulty). On average, motor symptoms were assessed within 61.33 ± 63.24 days of the neuropsychological evaluation (range = 0–365 days).

    2.7. Statistics

    We used SPSS Version 26 to conduct all the following analyses [60]. We examined demographic variables, clinical characteristics, and cognitive composites for normality and outliers, both visually and statistically. Most variables were not normally distributed—as assessed by histogram inspection, Z-tests of skewness/kurtosis, and Kolmogorov–Smirnov and Shapiro–Wilk normality tests (p’s < 0.05). Due to the non-normality of most variables, outliers were defined as scores falling outside 3x the interquartile range. No outliers were detected except for one participant having more years with PD symptoms (54 years) and another having severe depression (BDI = 54). As these two variables were supplementary to our primary aims, all cases were retained within analyses.

    Cochran’s Q test compared the PD-MCI prevalence rates using Bonferroni-corrected pairwise comparisons. We independently conducted K-means and Hierarchical cluster analyses (using Ward’s method and squared Euclidean distance) to cross-validate the cluster memberships. To examine the consensus of the two techniques’ cluster memberships, we used cross-tabulations and Pearson chi-square tests of independence.

    Using the optimal K-means cluster solution, we compared the derived clusters on demographics, clinical characteristics, and mood/motivation. Due to the clinical nature of our data, some measures were missing, so we used pairwise exclusion for these analyses. Because of the non-normal distribution of these variables, when comparing clusters, we used Kruskal–Wallis H tests (with Bonferroni-corrected pairwise comparisons) for continuous variables and Pearson chi-square tests of independence for categorical variables.

    Finally, to quantify the relationship between cluster membership and PD-MCI classification, we used Pearson chi-square tests of independence and binary logistic regressions. Because we aimed to examine the overlap between the prominently impaired cluster and PD-MCI classification, this cluster was used as the reference group in the regression models. Using the models’ sensitivity and specificity, we calculated Youden’s Index values for each cutoff [61]. We then calculated positive and negative predictive values assuming base rates based on the sample’s prevalence rates of PD-MCI and across the range of prevalence rates from previous studies.

    3. Results

    3.1. Sample Characteristics

    The database search identified 494 individuals meeting inclusion/exclusion criteria. Of these, 338 individuals had neuropsychological assessments performed as part of an evaluation for deep brain stimulation, and 156 individuals had cognitive testing as part of routine clinical care. These groups were largely similar in terms of cognitive performance (see Appendix A Table A1) and thus were treated as a single cohort for the analyses. Participants ranged in age from 38 to 87 years old, with an average age of 64.7 years (Table 2). Participants were well-educated, predominantly male (72%), and white non-Hispanic (94.3%), and had an almost 8-year duration of a PD diagnosis on average. Participants were generally in the early-mid stages of disease severity based the H&Y and the UPDRS Part III. The majority were characterized as the tremor predominant subtype (76.5%), while the rest of the sample were characterized as akinetic-rigid (22.5%) or postural instability and gait difficulty (1.1%). As a group, participants’ DRS-2 total scores were far above the dementia cutoff [37]. The average performance on indices of depression (BDI-II), apathy (AS), and anxiety (STAI) was below clinical cutoff, though there was substantial variability across participants.

    Table 2

    Sample Descriptive Characteristics.

    MeasureOverall Sample (n = 494)
    VariableMean/% (SD)
    Age64.73 (9.04)
    Education (years)15.01 (2.79)
    % Male72%
    % White, non-Hispanic94%
    Years since diagnosis7.84 (4.94)
    Years since symptom onset9.61 (5.26)
    PD motor subtype
    Tremor predominant77%
    Akinetic-rigid22%
    PIGD1%
    UPDRS III, on medication25.28 (9.80)
    Hoehn and Yahr (H-Y) Scale ^
    00.30%
    11%
    1.51%
    258%
    2.521%
    315%
    43%
    BDI-II, raw total10.10 (6.86)
    STAI: State anxiety, percentile61.33 (29.87)
    STAI: Trait anxiety, percentile58.38 (30.73)
    Apathy scale, raw total11.22 (6.31)
    Dementia Rating Scale-2, raw total136.99 (4.49)
    Cognitive composites (z-scores) #
    Executive function−0.58 (0.90)
    Verbal delayed memory−0.36 (1.01)
    Language−0.03 (0.96)
    Visuospatial abilities0.01 (0.78)
    Attention/working memory0.18 (0.77)

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    3.2. Prevalence of PD-MCI and Subtypes

    The prevalence of PD-MCI was 40.1% (n = 198) when using −1 SD cutoff, 21.5% (n = 105) when using the −1.5 cutoff, and 9.1% (n = 45) when using the −2 SD cutoff. There was a significant difference between the proportions of PD-MCI classified cases based on cutoff criteria, with a large effect size (χ2(2) = 563.10, p < 0.001, η2 = 0.66) and differences in the expected direction (p’s < 0.001).

    Across all three cutoffs, most PD-MCI cases had single-domain impairments (−1 SD: 64.59%, −1.5 SD: 77.0%, −2 SD: 80.22%) (Figure 1). Single-EF was the most common PD-MCI subtype. However, a notable portion of cases fell into non-EF subtypes (−1 SD: 19%, −1.5 SD: 19%, −2 SD: 26%). Classification into these other subtypes was primarily driven by memory and language deficits. Of the PD-MCI cases, when using the −1, −1.5, and −2 SD cutoffs, 33%, 25%, and 31% had memory deficits, and 17%, 15%, and 11% had language deficits, respectively.

    3.3. Cluster-Derived Cognitive Phenotypes

    Results of the K-means cluster analysis supported the existence of three clusters. Cluster membership was stable after 10 iterations. None of the clusters were unacceptably small. Visual inspection of the cluster centers (Figure 2) revealed a group with average cognition across all domains (n = 154), a group with low executive function (Low EF) (n = 227), and a group with executive function and memory impairments, as well as low language scores (Prominently Impaired EF/Memory) (n = 113).

    The hierarchical cluster analysis supported the use of two or three clusters based on the changes in agglomeration coefficients. When examining the proportions of cases assigned to the same cluster by both clustering methods, the three-cluster solution had highest agreement (84.41%), relative to the two and four cluster solutions (78.34%, 58.70%, respectively), and far exceeded the 25% greater than chance threshold. Using K-means as the standard, there was agreement on 89.61% (n = 138) of the Cognitively Average group, 83.36% (n = 189) of the Low EF group, and 79.67% (n = 90) of the Prominently Impaired EF/Memory group. There was a significant relationship between the likelihood of being assigned to the equivalent group using both clustering methods (χ2(4) = 598.73, p < 0.001). Thus, the three K-means clusters were determined to be the optimal cluster solution and were used in all subsequent analyses.

    Table 3 depicts the demographic, cognitive, mood, and motor scores of the three cognitive clusters. Results of Kruskal–Wallis H tests indicated that the three clusters significantly differed across DRS-2 total scores and all cognitive composite scores in the expected direction. Specifically, participants in the Cognitively Average group performed better than those in the Low EF group, who performed better than those in the Prominently Impaired EF/Memory group across all cognitive indices.

    Table 3

    Comparing the K-means Clusters’ Descriptive, Clinical, and Cognitive Characteristics.

    Characteristic
    Measure
    Cluster 1
    Cognitively Average
    Cluster 2
    Low EF
    Cluster 3
    Prominently Impaired EF/Memory
    Omnibus Kruskal–
    Wallis
    H-Test
    Effect SizePost hoc
    Differences (Bonferroni Corrected)
    N = 154N = 227N = 113
    Mean (SD)/Mean (SD)/Mean (SD)/p-valueEta squared /Cramer’s V #
    %%%
    Age (years)64.51 (8.75)65.31 (9.12)63.85 (9.15)0.380.004--
    Education (years)15.35 (2.55)14.91 (2.91)14.73 (2.83)0.130.01--
    Sex (% Male)68%73%75%0.33 ^0.07 #--
    % Caucasian, Non99%93%91%0.01 ^0.15 #1 < [2 = 3] *
    Hispanic
    % H-Y Stages 2–395%93%95%0.57 ^0.06 #-
    % Tremor Subtype73%76%82%0.16 ^0.08 #--
    Years Since Symptom9.45 (5.14)9.51 (5.20)10.03 (5.57)0.580.002--
    Onset
    Years Since Diagnosis7.70 (5.06)7.58 (4.73)8.56 (5.15)0.230.01--
    UPDRS Part III22.78 (8.85)25.18 (9.38)28.91 (10.81)<0.0010.05[1 = 2] < 3 **
    BDI-II9.15 (7.04)9.81 (6.06)12.09 (7.79)0.0010.031 < 3 **
    Apathy Scale10.47 (6.33)10.89 (6.25)13.01 (6.14)0.010.02[1 = 2] < 3 **
    STAI: State Pct.53.20 (31.34)63.26 (28.51)68.73 (28.09)<0.0010.041 < [2 = 3] **
    STAI: Trait Pct.50.11 (31.29)59.21 (30.30)68.33 (27.73)<0.0010.041 < 2 < 3 **
    DRS-2139.54 (3.10)136.92 (4.22)133.65 (4.42)<0.0010.231 > 2 > 3 *
    Cognitive Domain
    Z-Score Composites
    Executive Function0.20 (0.59)−0.58 (0.58)−1.63 (0.65)<0.0010.561 > 2 > 3 *
    Memory0.51 (0.70)−0.44 (0.75)−1.40 (0.75)<0.0010.471 > 2 > 3 *
    Language0.79 (0.68)−0.08 (0.70)−1.02 (0.72)<0.0010.481 > 2 > 3 *
    Visuospatial Skills0.44 (0.56)0.01 (0.70)−0.59 (0.82)<0.0010.211 > 2 > 3 *
    Attention/WM0.67 (0.70)0.03 (0.72)−0.20 (0.63)<0.001 0.201 > 2 > 3 **

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    As shown in Table 3, the three clusters also differed with respect to motor symptom severity, self-reported mood symptoms, and racial/ethnic distribution. Namely, participants in the Prominently Impaired EF/Memory cluster had significantly greater motor symptoms (UPDRS Part III scores), greater apathy (AS), and greater trait anxiety (STAI: Trait) than both other clusters and greater depressive symptoms (BDI-II) than the Cognitively Average cluster. Those in the Low EF and Prominently Impaired EF/Memory clusters had significantly greater state anxiety (STAI: State) than the Cognitively Average cluster. Moreover, there was a significant difference between the clusters’ proportions of white non-Hispanic participants, with a fewer represented in the Cognitively Average cluster relative to both other clusters. In contrast, there were no significant differences among the clusters across other demographic characteristics (age, education, sex), duration of illness (years since diagnosis, years since symptom onset), or proportion of participants with each motor subtype. Overall, the Prominently Impaired EF/Memory cluster had significantly worse mood, motivation, and motor symptoms than the other two clusters, but the effect sizes of these differences were small. As a follow-up, we conducted Pearson correlation analyses between the cognitive composites and mood/motivation measures (See Table A2 for analyses). Overall, the results continued to suggest an exceptionally small but consistent relationship between greater mood symptoms and worse cognitive performance across domains. Additionally, we conducted exploratory analyses within the language domain to determine whether one of the two measures drove the low language performance seen within the Prominently Impaired EF/ Memory cluster. We found that semantic fluency performance was significantly lower than confrontation naming (see Table A3).

    3.4. Relationship between Cognitive Phenotypes and PD-MCI Classification

    Table 4 depicts the distribution of PD-MCI cases within each cluster using the three PD-MCI impairment cutoffs. Pearson chi-square tests of independence revealed that PD-MCI classification and cluster membership were significantly related to one another with a large effect size (Table 4). Across all three cutoffs, the Cognitively Average cluster contained very few PD-MCI cases. Using the −1 SD cutoff, the Low EF and Prominently Impaired EF/Memory clusters contained similar portions of the PD-MCI cases. Using the −1.5 SD cutoff, about three quarters of the PD-MCI cases fell into the Prominently Impaired EF/Memory cluster while about a quarter fell into the Low EF cluster. Finally, using the −2 SD cutoff, almost all the PD-MCI cases fell into the Prominently Impaired EF/Memory cluster. Thus, the more stringent the impairment cutoff, the more sensitive the Prominently Impaired EF/Memory cluster was to containing greater portions of the PD-MCI classified cases.

    Table 4

    Percentage of PD-MCI Cases Falling to Each K-Means Cluster.

    Impairment CutoffCognitively
    Average
    % (n)
    Low EF
    % (n)
    Prominently Impaired EF/Memory
    % (n)
    Pearson Chi Square p-ValueCramer’s V
    −1 SD1.01% (2)46.46% (92)52.53% (194)223.47<0.0010.67
    −1.5 SD0.95% (1)23.81% (25)75.24% (79)213.13<0.0010.66
    −2 SD0% (0)4.44% (2)95.56% (43)148.33<0.0010.55

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    Binary logistic regression analyses examined how well cluster membership predicted PD-MCI classification. Each impairment cutoff had significant omnibus tests (−1 SD: X2(2) = 274.61, p < 0.001, Cox and Snell R2 = 0.43, Nagelkerke R2 = 0.58; −1.5 SD: X2(2) = 203.37, p < 0.001, Cox and Snell R2 = 0.34, Nagelkerke R2 = 0.52; −2 SD: X2(2) = 128.35, p < 0.001, Cox and Snell R2 = 0.23, Nagelkerke R2 = 0.50). The models all had large effect sizes, explaining between 50–58% of the variance in PD-MCI classification, and cluster membership was a significant predictor in all three impairment cutoff models.

    Using the −1 SD cutoff, those in the Cognitively Average cluster had 1000× lower odds of being classified as PD-MCI, relative to the Prominently Impaired EF/Memory cluster, while those in the Low EF cluster had 16.95× lower odds (p’s < 0.001; Cognitively Average cluster’s 95% Confidence Interval (CI): 200-perfect model fit; Low EF’s 95% CI: 8.29–35.71). This model correctly classified 79.1% of PD-MCI cases with poor sensitivity (as only about half of PD-MCI cases were classified as such by the model) and excellent specificity (as almost all Cognitively Average cluster participants were correctly classified as cognitively normal by the model; Table 5). Using the −1.5 SD cutoff, those in the Cognitively Average cluster had 333.33× lower odds of being classified as PD-MCI, relative to the Prominently Impaired EF/Memory cluster, while those in the Low EF cluster had 18.87× lower odds (p’s < 0.001; Cognitively Average’s 95% CI: 47.62-perfect model fit; Low EF’s 95% CI: 10.53–33.33). This model correctly classified 87.9% of PD-MCI cases with stronger sensitivity and slightly lower (but still excellent) specificity than the −1 SD criteria model. Finally, using the −2 SD cutoff, those in the Low EF cluster had 71.43x lower odds of being classified as PD-MCI, relative to the Prominently Impaired EF/Memory cluster, while no cases in the Cognitively Average cluster were classified as PD-MCI (Low EF p < 0.001, 95% CI: 16.39–333.33). This final model correctly classified 90.9% of PD-MCI cases, but the model predicted that all cases were cognitively normal, leading to a null sensitivity and perfect specificity.

    Table 5

    Binary logistic regression models’ sensitivity, specificity, and positive and negative predictive values based on different PD-MCI prevalence rates.

    Impairment CutoffSensitivitySpecificityC Stat.Sample0.25Base Rate
    0.45
    0.65
    PPV NPVPPV NPVPPV NPVPPV NPV
    −1 SD0.530.970.860.920.760.850.860.940.720.970.53
    −1.5 SD0.750.910.880.700.930.740.920.870.820.940.66
    −2 SD0.001.000.91--0.91--0.75--0.55--0.35

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    When using the models’ predicted PD-MCI group membership to predict actual PD-MCI classification, all three models produce significant, acceptable C statistics (above 70%, p’s < 0.001; Table 5). The model using the −1.5 SD cutoff had the highest jointly maximized sensitivity and specificity (−1 SD Youden’s Index (YI): 0.50; −1.5 SD YI: 0.66; −2 SD YI: 0). Table 5 presents the positive and negative predictive values predicated on a range of PD-MCI base rate estimates. Using the sample’s prevalence rates for each cutoff, the −1 SD cutoff maximizes the probability that those classified by the model as PD-MCI truly meet this actuarial diagnosis while the −1.5 SD cutoff maximizes the probability that those classified as cognitively normal are truly cognitively intact. Since the true base rate of PD-MCI is unknown, the low, midpoint, and high end of the range of estimated prevalence rates were also used to calculate positive and negative predictive values [25,26]. In settings with lower PD-MCI prevalence rates (e.g., 25%), using −1 SD would jointly maximize the probability of correct classification, but in settings containing a population with greater chance of impairment (e.g., 45%), then −1.5 SD would do so. As our patients were all seen in a specialty clinic, the prevalence of PD-MCI in our sample is presumably closer to this midpoint of the prevalence rates previously estimated. Taken all together, using the −1.5 SD cutoff resulted in cluster membership having high model-based classification accuracy, the largest YI, and jointly maximized PPV/NPV (based on our sample’s clinical setting).

    4. Discussion

    Our study investigated different techniques of methodologically defining and characterizing cognitive impairment in a large, clinical sample of individuals with idiopathic PD without dementia. We took two approaches (i.e., actuarial PD-MCI classification, cluster analytic) and looked at their overlap. In doing so, we hoped to learn which cognitive phenotypes empirically emerged, the influence of different impairment cutoffs on PD-MCI prevalence rates, and whether a specific impairment cutoff aligned best with the cognitive phenotype reflecting greater PDD risk.

    The actuarially defined PD-MCI prevalence varied from 40.1% using the liberal end of impairment criteria (−1 SD), to 21.5% using the midpoint (−1.5 SD), and 9.1% using the conservative end (−2 SD). Regardless of impairment cutoff, most PD-MCI cases involved single-domain impairment. This finding aligns with that of Marras and colleagues [62] and runs counter to that of others who describe PD-MCI as most commonly involving multi-domain impairment [25,62,63]. This discrepancy likely reflects methodological differences. For example, if one strictly follows proposed criteria for MCI by the Movement Disorder Society (MDS) [23], then having a single impaired test across two separate domains leads to the designation of multi-domain PD-MCI. In contrast, other more psychometrically rigorous approaches require participants to have at least two impaired measures within a domain for it to be considered impaired. Marras and colleagues [62] found that when strictly using MDS criteria, most PD-MCI cases demonstrated multi-domain impairment; however, when they analyzed the same sample with an altered operationalization of impairment that required two impaired tests within a domain, the majority of PD-MCI cases had single domain impairment. Thus, using a similarly more stringent operationalization of impairment, our results support the commonality of the single-domain impairment in a larger sample of individuals with PD without dementia.

    In the current study, we grouped those classified as PD-MCI into executive vs. nonexecutive subtypes, with presence or absence of other co-occurring cognitive difficulties (e.g., EF—single domain, EF—multi-domain). This method of subtyping allowed us to distinguish the variety of cognitive domains impaired beyond executive dysfunction. Using this approach, we found, across all three cutoffs, the Single-EF subtype was the most prevalent, but 19–26% of PD-MCI cases (depending on the cutoff) exhibited impairments only in other domains-reinforcing the existence of variable patterns in cognitive performance across individuals with PD. Beyond the most prevalent deficit, executive dysfunction, participants primarily demonstrated deficits in memory and language domains.

    Using a different statistical approach (cluster analysis), we found three distinct cognitive phenotypes in this same sample of individuals with PD. These phenotypes differed in severity of cognitive deficits: (1) average cognition, (2) low EF, and (3) more prominent impairments in EF and memory with low language abilities. Though this is a cross-sectional study, it is possible that these phenotypes may reflect the succession of neuropathological changes. Namely, individuals with PD develop frontal executive dysfunction based on dopaminergic changes in frontal-striatal networks and, as the disease progresses, more cortical system and limbic deficits develop (based on cholinergic changes) [29,30,31]. With disease progression, individuals with greater cognitive deficits may have more widespread involvement of cortical areas which likely increases their risk of transitioning to PDD. This notion was recently supported by Domellöf and colleagues [64] who found that significantly lower performance on semantic fluency, memory, and EF measures, identified individuals with PD-MCI who converted to PDD over a five-year period. Thus, our broadly impaired cluster contained multiple deficits previously shown to be predictive of progression to PDD.

    Participants in the more prominently impaired cluster demonstrated worse motor symptoms (UPDRS-Part III scores) than the other two clusters. This finding is in alignment with previous research showing greater cognitive dysfunction (including dementia risk) in those with more advanced motor symptoms and disease progression [65,66,67]. The prominently impaired cluster also had greater mood symptoms relative to the other two clusters. While the influence of mood is likely a contributing component to their performance, the cluster differences had small effect sizes, suggesting a minimal impact of mood on cluster membership. We did not find broad evidence for demographic differences between the three clusters, a finding that conflicts with prior research that older age, less education, and longer disease duration are associated with worse cognition [68,69,70]. Of note, the cognitive clusters were based on composite scores of “normed” neuropsychological measures, which controls for certain demographic factors. As such, the norming might obfuscate findings of age, and potentially education, differences across the cluster phenotypes. We did find that the cognitively average cluster had a greater proportion of white non-Hispanic participants; however, the small sample sizes of other races/ethnicities in the overall sample limit our ability to draw related inferences.

    Finally, the outcomes of the data-driven and theoretical approaches were compared. We found that the midpoint cutoff (−1.5 SD) served as the best predictor of PD-MCI classification relative to the other cutoffs in terms of classification accuracy and jointly maximized sensitivity and specificity of the model. Use of the midpoint (−1.5) cutoff resulted in three-fourths of the PD-MCI cases falling into the prominently impaired cluster, whereas use of liberal (−1 SD) cutoff resulted equivalent distribution of PD-MCI cases into the low EF and prominently impaired clusters. Researchers previously tried to validate the same three PD-MCI impairment cutoffs by comparing them against clinical diagnosis, but findings have been inconsistent, supporting cutoffs at either −1.5 SD [71] or −2 SD [8]. Furthermore, these clinical validation methods use a circular logic in that clinical diagnosis of impairment would still require a preconceived understanding of what performance counts as impaired relative to a normative expectation. Comparing actuarial and empirical approaches serves as a validation method that circumvents this circular logic. This methodology has precedence within the Alzheimer’s literature which found that data-driven approaches may enhance sensitivity for detecting both cross-sectional and future clinical, biomarker, and neuropathological outcomes-a topic that should be explored in future work with PD participants.

    Past longitudinal work evaluating which impairment cutoff best predicts PDD development over a multi-year follow-up period also remains mixed-with some studies supporting an optimal cutoff at −1.5 SD [27] while others support a cutoff of −2 SD [72]. Though cross-sectional, our findings further support the use of a midpoint (−1.5 SD) cutoff based on its validation against the sample’s cognitive phenotype with deficits that past studies suggest are predictive of PDD.

    This study has limitations. First, our clinical sample may not be representative of a broader population of individuals with PD as our data were collected at a specialty center from a combination of patients seeking deep brain stimulation and those referred for a neuropsychological evaluation due to cognitive concerns. Second, while patients were clinically diagnosed with PD using established clinical criteria, this patient population did not have pathologically confirmed PD (to definitively rule out other syndromes that could mirror PD early on, such as Progressive Supranuclear Palsy-Parkinsonism Predominant variant). Third, we did not have access to the whole sample’s medication information that would enable us to characterize the potential relationship of cognitive performance with medications (e.g., parkinsonian medication’s LEDD values, or rate of anticholinergic use). A small subset of recently seen patients (n = 20/cluster) had available medication lists, from which Magellan Anticholinergic Risk Scale scores were calculated [73]. A chi-square test of independence showed no significant differences in the proportions of Magellan scores across clusters and weak effect size (p = 0.516, Cramer’s V = 0.20), suggesting that our predominantly impaired group did not have a significantly disproportionate amount of participants on anticholinergic medication. Fourth, we used listwise exclusion to meet the goal that all participants have two or more measures within each domain to classify them as PD-MCI. There is a possibility that we may have missed more severely impaired individuals who did not complete the full battery of tests, though these individuals would have likely been excluded based on our cognitive screener.

    More broadly, there are some issues involving current practices used for formal clinical diagnosis of MCI. One practice is the requirement that patients have subjective cognitive complaints in order to receive MCI diagnosis (as in the MDS PD-MCI consensus criteria). We did not have this information readily available, and not applying this broadly used MDS criteria limits the comparability of our findings to other studies that use it. Even so, there is precedence for not including subjective cognitive complaints within an actuarial version of the PD-MCI criteria [7,74,75,76], and evidence for the usefulness of this criteria is mixed [77,78]. Finally, clinicians often make a diagnosis of MCI in situations where there has been a performance drop from an estimated premorbid baseline (e.g., a, drop from superior to low average ranges). We were unable to account for impairment based on decline from premorbid abilities in this sample. However, defining MCI with actuarial methods has gained traction within the Alzheimer’s literature and been shown to improve diagnostic rigor for MCI [22,79,80,81]. Thus, further research examining actuarial methods to characterize PD-MCI may prove helpful in establishing a “gold standard” and “true” prevalence rates.

    Future work should expand to a more racially/ethnically diverse sample with wider levels of educational attainment to better generalize the results to a broader patient population. It would also be helpful to conduct a longitudinal study to evaluate which impairment cutoff best predicts PDD development in a larger sample than previous studies.

    5. Conclusions

    The current findings add to the literature by demonstrating the utility of comparing empirical and classification definitions of cognitive impairment. Our results reinforce that variability in prevalence rates of actuarially-defined PD-MCI stems, in part, from use of different normative definitions of impairment (e.g., −1 to −2 SD). Although this may seem trivial, it dramatically affects prevalence rates and in turn influences predictive validity of dementia. Yet, across all cutoffs, PD-MCI classified cases most commonly exhibited single-domain deficits (primarily in executive function). When empirically defining patterns of cognitive impairment in a large clinical sample, we found three distinct cognitive phenotypes with differing levels of cognitive deficit severity. The cognitive phenotype with broader, more prominent impairments (including features suggestive of greater risk of impending PDD development) best aligned with operationalizing impairment at the midpoint cutoff (−1.5 SD). These findings contribute to the widespread efforts to determine criteria that best establish what level and which patterns of cognitive impairment have the most utility at predicting who is at greatest risk of upcoming progression to PDD.

    Appendix A. Comparison of Deep Brain Stimulation and General Clinic Patients’ Cognitive Performance

    Table A1

    Cognitive performance of deep brain stimulation candidates versus general clinic patients.

    MeasureDBSGeneral ClinicSignificance
    (n = 338)(n = 156)
    Mean (SD)Means (SD)p-value
    Dementia Rating Scale-2, raw total137.05 (4.28) 136.86 (4.92) 0.69
    Cognitive Composites (z-scores) #
    Executive Function−0.55 (0.88)−0.64 (0.93)0.32
    Verbal Delayed Memory−0.37 (1.00) −0.36 (1.04)0.95
    Language0.001 (0.94) −0.09 (1.00)0.35
    Visuospatial Abilities0.01 (0.78) 0.02 (0.79) 0.85
    Attention/Working Memory0.20 (0.77) 0.11 (0.76) 0.22

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    Appendix B. Relationship between Mood and Cognitive Domains

    Table A2

    Pearson correlations between mood measures and composite z-scores.

    MeasureExecutive FunctionVerbal
    Delayed Memory
    LanguageVisuospatialAttention/
    Working Memory
    BDI-II−0.10 *−0.13 *−0.09 *−0.10 *−0.16 *
    STAI
    State−0.18 *−0.10 *−0.18 *−0.10 *−0.08
    Trait−0.18 *−0.15 *−0.17 *−0.14 *−0.15 *
    Apathy Scale−0.14 *−0.10−0.09−0.13 *−0.09

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    Greater depressive symptoms (BDI-II) and dispositional anxiety (STAI-Trait) were both significantly associated with poorer performance across all composites, with small effect sizes. Greater situational anxiety (STAI-State) significantly related to worse performance on all composites except attention/working memory, with small effect sizes, and greater apathy symptoms (AS) significantly correlated with poorer performance on executive and visuospatial composites.

    Appendix C. Exploratory Analyses of Language Metrics

    Table A3

    Z-scores of Language Metrics across Clusters.

    MetricCognitively AverageLow EF Prominently Impaired EF/Memory
    Boston Naming Test1.05 (0.96)0.18 (1.01)−0.67 (0.96)
    Semantic Fluency (Animals)0.52 (0.90)−0.35 (0.96)−1.37 (1.04)

    Open in a separate window

    Table A3 shows mean scores of BNT and semantic fluency (Animals) across the 3 clusters. Results of a between (cluster) x within (language measure) repeated measures ANOVA revealed a significant main effect of language measures (F(1.00, 491.00) = 95.94, p < 0.001, np2 = 0.16) where semantic fluency was significantly lower than confrontation naming (M = −0.65, p < 0.001). The main effect of cluster was also significant (F(2, 433.61) = 202.84, p < 0.001), with the Cognitively Average cluster performing significantly better than the Low EF cluster (M difference = 0.87) who in turn scored better than the Prominently Impaired EF/Memory cluster (M difference = 0.78), with all p values < 0.001. The cluster x language measure interaction was nonsignificant (F(2.00, 491.00) = 0.50, p > 0.05, np2 = 0.002). Thus, all clusters demonstrated similar patterns of worse semantic fluency performance relative to confrontation naming.

    Author Contributions

    Conceptualization, L.E.K. and D.B.; Data curation, L.E.K.; Formal analysis, L.E.K., A.M.R. and F.V.L.; Funding acquisition, C.C.P. and D.B.; Methodology, L.E.K., C.C.P., M.J.A. and D.B.; Supervision, C.C.P., M.J.A. and D.B.; Visualization, L.E.K.; Writing—original draft, L.E.K.; Writing—review and editing, L.E.K., A.M.R., F.V.L., C.C.P. and M.J.A. and D.B. All authors have read and agreed to the published version of the manuscript.

    Funding

    This project was supported by the Norman Fixel Institute for Neurological Diseases and partially supported by the National Institutes of Health (Grant number: T32-NS082168, Grant number: R01NS082386, Grant number: K07AG066813).

    Institutional Review Board Statement

    The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the University of Florida (protocol code 211701522 and date of approval 6/22/2017).

    Informed Consent Statement

    Informed consent was obtained from all subjects involved in the study.

    Data Availability Statement

    The datasets presented in this article are not publicly available because an inquiring party must submit a request to the UF INFORM database committee at the Norman Fixel Institute of Neurologic Diseases, and this request must be approved by the UF IRB. Requests to access the datasets should be directed to “Chuck Jacobson, [email protected]”.

    Conflicts of Interest

    The authors declare no conflict of interest with respect to this study.

    Footnotes

    Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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    Nice flight

    Flight was on time but seat was very uncomfortable.

    Overall, no major problems and all employees were great. The gate area was not large enough for the passengers, so people congregated in the walkway or sat in a different area, which is slightly burdensome because you can’t hear announcements elsewhere. But this is an airport not airline issue and nothing in the short term could address it.

    I will be very glad when this mask business is over.

    More leg room.

    Cons: "1ST CLASS IS WAY OVERRATED Uncomfortable seats, very rude flight attendants they should not be in the service/hospitality industry!"

    Pros: "The pilot was hilarious and his jokes really helped calm the situation when there was crazy turbulence"

    Cons: "No beverages available to even purchase ! Ridiculous!"

    Pros: "Smooth flight, great service onboard"

    Cons: "Your seats are too small, but we know the airline industry is not gonna do anything about it."

    Pros: "Crew!"

    Cons: "Food availability."

    Pros: "Yes"

    Cons: "Everything was fine"

    Pros: "The food and the movies!"

    Cons: "The air on the plane was stale and I could barely breathe the entire flight. I feel sick and light headed after that one."

    Cons: "The cabin was way too cold."

    Pros: "Responsive and helpful crew. Comfortable seating."

    Cons: "More snacks; maybe coffee or a second round of refreshments. Not much, really; it was a great experience under the circumstances."

    Pros: "Left on time"

    Cons: "Customer service was bad"

    Pros: "The service was great"

    Cons: "That you have to pay extra for entertainment, that you have to have your own device, and that the food was mediocre"

    Pros: "The flight was shorter than we expected! And after a long flight that was most appreciated."

    Pros: "plane had wifi"

    Cons: "multiple gate changes multiple delays boarded and then sat on the plane never pushing back from gate"

    Cons: "Long delays"

    Cons: "did not get my requested wheel chair service."

    Pros: "All good, on time, crew was pleasant!"

    Cons: "All good"

    Cons: "We taxied on the runway for 45 minutes. Grrr"

    Pros: "Flight depart on time, with possible 5 minute delay. No problem at all."

    Pros: "Drink service was good"

    Pros: "Paid extra for more legroom"

    Cons: "No Free WiFi"

    Pros: "Personalities...loved their job. Great to talk to."

    Cons: "Bosrdunf staff at DCA. No communication in crowded area"

    Pros: "i loved everything but there should be more variety of food and snacks"

    Cons: "nothing"

    Pros: "Flight on time ."

    Pros: "Good service and excellent crew"

    Cons: "Food choice are few by the time they reach the back of the plane."

    Pros: "Gate attendant kept us informed frequently as to the status of the flight"

    Cons: "Rudeness/snappiness of the stewardesses"

    Pros: "I loved the extra room in the seating, great seats too. Plus the personal TVs and movie selection was fantastic!!! However, 1/3 of the planes TVs did not work. Luckily, my row of TVs did work and we had an empty seat between my daughter and me , so when my son's TV went out he sat in my row which did work. Great plane, once everything is fixed!"

    Cons: "I did not like that the airline would not give a seat on an earlier flight so that I would not have to spend so many hours in the Chicago O'Hare airport. I did not like that the airport only allowed me thirty minutes of access to the internet. As a result, I could not work while I had to wait for my flight. Finally, I did not like that the airline lost or delayed my bag."

    Cons: "Flight was 1.5 hours delayed with another 1 hour delay on the tarmac"

    Pros: "Boarding and debar king was quick."

    Cons: "Attendant was surly, no coffee, no continental breakfast as indicated on the reservation. Very disappointed with in-flight service."

    Cons: "Cramped seating. As per usual."

    Pros: "No fees for carryon, like Republic charged on the way out"

    Cons: "NO seats available on booking, without paying extra. Never could sit together, even though booked together. Greedy but stupid."

    Pros: "On time departures. Friendly crew."

    Cons: "Nothing"

    Pros: "Long wait for take off. Everything else was great."

    Pros: "The ticketing staff in Lihue was excellent!"

    Pros: "We had a wonderful flight experience. Smooth take off and landing. The in flight service was impeccable! Will definitely be flying American Airlines again."

    Cons: "Because it was a day later!!!"

    Pros: "Much better than the trip to chicago"

    Pros: "The price is competitive. On boarding was ontime. Though the flight was redirected to Omaha due to bad weather in Kansas City, it was only an hour late than the scheduled arrival to Kansas City."

    Cons: "The WiFi was not as expected. In flight entertainment is null. Snack would have been better."

    Pros: "very good no problems.."

    Cons: "all good thanks much"

    Pros: "Flight was delayed but boarding at DCA was very efficient and quick"

    Cons: "Flight attendants seemed bothered by something and weren't very nice. They looked/seemed tired. Cabin lights were on the whole time for a ~3 hour flight which began at 830pm."

    Pros: "Crew very courteous"

    Cons: "Flight was delayed 2 hours. I couldn't run my business that way!"

    Pros: "On time..."

    Cons: "No phone charging at seats, no personal video in setback..."

    Pros: "The flights weren't delayed and were right on time."

    Cons: "Both flights were on time."

    There is nothing great about air flight any more. If you are traveling in economy you are cattle. The staff of the airport and United were fine. The seating was ridiculously small. I am 5’2 and was uncomfortable. You cannot recline the seat for fear of upsetting the person behind you, You can get a soda but for anything else you pay. My husband is a tall man at 6’4” and he was totally uncomfortable. If you can afford too, opt for the premium plus seat for just al little more leg room. Air travel is just not what it was. My advice, go to the airport early, use the check-in for your luggage, go paperless and have all your necessary information on your phone and in hand, have a good attitude and stay calm. You are going to be uncomfortable and most likely delayed so don’t stress

    Pros: "Worst flight ever!! 7 hour delay because the plane broke down!! Never fly United again!!"

    Cons: "They should have offered free flight vouchers!! We got a lousy $20 meal voucher after waiting for 7 hours, delay was originally 1 hr then 2 then 3 etc On Father’s Day, it was the worse day ever!!"

    Pros: "Crew was terrific"

    Cons: "Cabin was a little cool"

    Pros: "The crew was great. The flight arrived on time even though there was a mechanical delay."

    Cons: "Very very delayed. Made traveling home difficult on me and my family."

    Cons: "Didn't realize when we booked our seats that they were basic economy and we couldn't upgrade or change them. I was seated away from my husband, beside a very large man who hugged the armrest and munched loudly on corn chips. For 5 hours. Movie headphones were poor. No leg room and I'm 5'4", 125 lbs."

    Cons: "The delay was horrible and the captain said it was because they needed extra sleep. I found this offensive as i was trying to complete a very long trip and was exhausted."

    Cons: "First class seat and it barely reclined at all"

    Pros: "Friendly crew"

    Cons: "Very cramped and uncomfortable seats in Economy. 2 hours late arriving in KansasCity."

    Pros: "The variety of movies"

    Cons: "No daily wifi"

    Pros: "quick fast and no nonsense, nothing to worry about on a 30 minutes. Hawaiian gets you there fast and mostly on time."

    Pros: "Going home"

    Pros: "The gate agent kept us well informed about our delayed flight - she kept calling to find out status of the flight and reported her findings to us after every call. United provided water and snacks in the gate area as we waited. Gate agent was pleasant and helpful to everyone during the delay."

    Cons: "Got a call at 3:00 am saying our flight would be delayed an hour from 1:00 pm to 2:00 pm. and offered optional flights at no charge. Stayed with original flight since this was a direct flight. The flight ended up being 3 1/2 hours late. We had to wait for a ferried plane from Chicago. Just wondering if United knew at 3:00 am that they had problems, why did it take 13 hours for them to resolve it?"

    Pros: "The plane took of and arrived safely and on time. The entertainment was decent."

    Cons: "1/2 bag of pretzels for a ~6 hour flight? Are you kidding me! The whole ride was sweltering hot. United flight attendants almost universally hate their jobs and they let it show. The entertainment system takes up half of the room under the seat, as if things weren’t cramped enough already."

    Cons: "We boarded the plane and due to "mechanical problem", we sat on the tarmac for ~3 hours before departing. This led to missing our connection at LAX and then missing our connection in ORD to State College tacking 6 extra hours to the trip. The late arrival and full work schedule the next day left me exhausted and got a nasty cold as a consequence. I find the frequency of mechanical problem delays to be high and increasing."

    Pros: "Smooth landing."

    Cons: "Nothing."

    Pros: "Nothing"

    Cons: "No compensation, no manager available because they were dealing with the same issue at another gate. Where is the customer service?"

    Pros: "Smooth easy flight."

    Cons: "The only real downside was seat 22D headphone jack was broken so it made for a long flight but I played some games."

    Pros: "Comfortable, quick, and great service."

    Cons: "No food."

    Cons: "No comment"

    Pros: "Nothing special"

    Cons: "Seats very dirty sticky Not clean at all"

    Cons: "Due to United delays in Bogota we were put on a standby flight 3 hours later. We didn't get on. Then had another connection two hours later that was delayed due to maintenance. Spent over 10 hours in airport. And over a total of 30 hours traveling ☹️"

    Pros: "The flight crew seemed worn and a bit surly. They ran out of two of the meals and the one I got was oddly seasoned but it was warm. We sat on the ground quite a while while they fixed the PA system with no water then there was a women they'd let on the flight even though she had a different destination - supposedly they spent an hour looking for her bag on the plane. Do you hold up a whole plane load of people that got on the right plane for the woman that didn't and how come when they checked her ticket - no one noticed?"

    Pros: "I paid extra for Economy Plus. That should be the standard seating."

    Cons: "Any flight where passengers have no chance to eat should provide more than a cookie."

    Pros: "Generally, a good flight experience. The crew were polite and professional."

    Pros: "We toured the Boeing plant in Everett (Seatle.) I wish I had bought a T-shirt I saw in the gift shop. It read, "If it ain't Boeing, I ain't going.""

    Cons: "Except in the row right behind 1st Class, the seats are kinda crammed (in.) On a commercial on one flight, during the spiel about safety, the movie screen showed about 5 or 6 cabin attendants putting up their trays in prep for landing. Tey all leaned forward as far as they could to reach their trays. I looked around. I could reach my tray with my arms at my sides. If the actual airplane had had it'w seats spaced apart as in the movie, the plane would have been fully loaded with some 35 passengers. I forgot what airline it was, maybe yours?"

    Pros: "Captain was communicative before departure and during flight Boarding was orderly"

    Cons: "After aircraft was parked a strange loud noise could have been heard for 30 seconds. Would be nice if a crew member (flight attendant or captain) assured passengers that it was normal. Noise didn't seem normal and I was very concerned. No infotainment options."

    Cons: "Kansas City airport is in need of a complete remodel."

    Pros: "That transportation was available in Chicago."

    Cons: "No problems."

    Cons: "Flight delayed"

    Pros: "The crew was again nice enough to find an empty seat next to mine."

    Cons: "The layover was very short. Fortunately, the gates were very close together. However, since I didn't have time to get lunch in the terminal, I had a snack box for lunch, too. This was rather monotonous. There aren't enough chocolate choices on the snack menu. There were no limes for my beverage. There was no in-flight entertainment available. I had hoped to finish the movie I started on the first leg."

    Cons: "The gate in Newark was a dump and the boarding process was chaotic"

    Pros: "on schedule even though ORD had some weather issues but yes good flight.."

    Pros: "Smooth flight and on time"

    Pros: "The free internet and movies"

    Cons: "The delayed flight"

    Cons: "Flight got cancelled cause of issues with plane. Took over 5 hours in line to get to the counter to talk to someone. There were only 2 counter people for first 3 hours. Once at counter ther had to put us on flight for next day. (Just informed 5 min ago that flight has been delayed another day cause of plane issues.) they couldn't get us to sit together which I understand but also put me in a middle seat which I'm clostraphobic so that sucks. Told me that I can book a hotel to stay at and they would reimburse me.... eventually. Fought over that for an hour and they finally agreed to pay for Hotel. Overall the trip was great but the departure from Kauai has been real bad. Still waiting to leave the island."

    Pros: "Very good"

    Pros: "Boarding and crew were good"

    Cons: "No comfort at all. Plane was jam packed and I had no leg room, arm rests would not come up, no free wifi or free entertainment."

    Cons: "Very uncomfortable seats with no leg room."

    Pros: "Good movie choices"

    Cons: "No food. Just some peanuts"

    Pros: "easy boarding, helpful united employees"

    Pros: "I really appreciate them getting us there safely the crew was fine and it was nice to have tvs on each seat complimentary it really helps having something else to take you away mentally when physically your crammed together and it's really not comfortable or pleasant. I think the staff and crew were just fine though it's just flying has gotten to be something I don't enjoy and want to avoid as much as possible it's that way with most airlines though I think her blue is a little better on seat space and usually always has the tvs but yeah they are limited where they fly and it I is just expensive and uncomfortable to fly I think."

    Cons: "Uncomfortable and expensive."

    Pros: "First class it was owsome"

    Pros: "Employees need to understand that many people who don't fly often have an anxiety about the whole process. Being friendly and helpful goes a long way in making the experience less of a hassle. United seems to understand this and for the most part their employees were very friendly and helpful. I will choose united whenever possible."

    Cons: "TSA employees need to lighten up. I think they can still do their job and be friendly at the same time. They all seem to hate their jobs"

    Cons: "United canceled my reservation without any explanation. The Worst customer service ever!!!!"

    Pros: "Cheaper"

    Cons: "Long boarding and delayed flight, lots of walking"

    Cons: "When I boarded the plane, I noticed crumbs and grease marks on my seat and crackers all over the floor at my feet. Rather than clean my area, the stewardess handed me wet wipes."

    Pros: "Delayed in Denver"

    Pros: "It's was quick."

    Cons: "Delayed a bit but mostly ok."

    Pros: "Chairs were comfortable on this plane"

    3x error m_ci null

    Mapping Actuarial Criteria for Parkinson’s Disease-Mild Cognitive Impairment onto Data-Driven Cognitive Phenotypes

    Logo of brainsci

    Lauren E. Kenney,1,2,*Adrianna M. Ratajska,1,2Francesca V. Lopez,1,2Catherine C. Price,1Melissa J. Armstrong,2,3 and Dawn Bowers1,2,3

    Melissa J, 3x error m_ci null. Armstrong

    2Norman Fixel Institute of Neurological Diseases, University of Florida, Gainesville, FL 32603, 3x error m_ci null, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32603, USA

    Find articles by Melissa J. Armstrong

    Dawn Bowers

    1Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32603, 3x error m_ci null, USA; [email protected] (A.M.R.); [email protected] (F.V.L.); [email protected] (C.C.P.); [email protected] (D.B.)

    2Norman Fixel Institute of Neurological Diseases, University of Florida, Gainesville, 3x error m_ci null 32603, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32603, USA

    Find articles by Dawn Bowers

    Pierluigi Zoccolotti, Academic Editor, Dona E. Locke, Academic Editor, and Andrea Loftus, Academic Editor

    Author informationArticle notesCopyright and License informationDisclaimer

    1Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32603, USA; [email protected] (A.M.R.); [email protected] (F.V.L.); [email protected] (C.C.P.); [email protected] (D.B.)

    2Norman Fixel Institute of Neurological 3x error m_ci null, University of Florida, Gainesville, FL 32603, USA; [email protected]

    3Department of Neurology, University of Florida College of Medicine, Gainesville, 3x error m_ci null, FL 32603, USA

    *Correspondence: [email protected]

    Received 2021 Nov 11; Accepted 2021 Dec 22.

    Data Availability Statement

    The datasets presented in this article are not publicly available because an inquiring party must submit a request to the UF INFORM database committee at the Norman Fixel Institute of Neurologic Diseases, and this request must be approved by the UF IRB. Requests to access the datasets should be directed to “Chuck Jacobson, 3x error m_ci null, [email protected]”.

    Abstract

    Prevalence rates for mild cognitive impairment in Parkinson’s disease (PD-MCI) remain variable, obscuring the diagnosis’ predictive utility of greater dementia risk. A primary factor of this variability is inconsistent operationalization of normative cutoffs for cognitive impairment. We aimed to determine which cutoff was optimal for classifying individuals as PD-MCI by comparing classifications against data-driven PD cognitive phenotypes. Participants with idiopathic PD (n = 494; mean age 64.7 ± 9) completed comprehensive neuropsychological testing. Cluster analyses (K-means, Hierarchical) identified cognitive phenotypes using domain-specific composites. PD-MCI criteria were assessed using separate cutoffs (−1, −1.5, −2 SD) on ≥2 tests in a domain. Cutoffs were compared using PD-MCI prevalence rates, MCI subtype frequencies (single/multi-domain, executive function (EF)/non-EF impairment), and validity against the cluster-derived cognitive phenotypes (using chi-square tests/binary logistic regressions). Cluster analyses resulted in similar three-cluster solutions: Cognitively Average (n = 154), Low EF (n = 227), and Prominent EF/Memory Impairment (n = 113). The −1.5 SD cutoff produced the best model of cluster membership (PD-MCI classification accuracy = 87.9%) and resulted in the best alignment between PD-MCI classification and the empirical cognitive profile containing impairments associated with greater dementia risk. Similar to previous Alzheimer’s work, these findings highlight the utility of comparing empirical and actuarial approaches to establish concurrent validity of cognitive impairment in PD.

    Keywords: Parkinson’s disease, mild cognitive impairment, movement disorders, cluster analysis, 3x error m_ci null, prevalence

    1. Introduction

    The experience of Parkinson’s disease (PD) encompasses not only the prototypical motor symptoms but also a plethora of non-motor symptoms including cognitive changes. Past research estimates that approximately 40% of people with PD have mild cognitive impairment (PD-MCI) at any given time, and up to 80% of individuals with PD will develop dementia after living with the disease for 15–20 years [1,2]. However, the trajectory of cognitive changes can differ among individuals with clear diagnoses of idiopathic PD—with some declining more rapidly than others [3]. Therefore, while the endpoint of the trajectory is known for many individuals with PD, 3x error m_ci null, the question remains who is most at risk for a more rapid transition to Parkinson’s disease dementia (PDD).

    Two lines of research aim to answer this question, 3x error m_ci null. Some studies take an empirical approach by statistically examining neuropsychological data to see what patterns of cognitive performance arise. This is often done via use of cluster analytic techniques, resulting in distinct clusters or cognitive phenotypes. Others take an a priori classification approach, meaning that mild cognitive impairment (MCI) is designated by specific impairment criteria, which are then used to identify patterns of deficits across cognitive tests or domains. One way of doing this is via “actuarial classification criteria”, defined as using objective, pre-established numerical definitions of impairment, rather than a consensus diagnosis or clinical judgment. Both empirical (cluster analytic) and actuarial/clinical theoretical classification approaches aim to characterize distinct cognitive profiles in PD-with the hope of subsequently determining if certain cognitive profiles or subtypes connote greater risk of developing PDD at faster rates.

    Recently, comparison of the predictive utility of these two types of approaches (cluster analysis vs. a priori classification) has gained traction among researchers in the MCI-Alzheimer’s disease (AD) literature. Indeed, recent studies have found that cognitive phenotypes derived from cluster analyses are more strongly correlated with AD biomarkers and are more strongly linked to dementia progression than traditional a priori classification methods [4,5]. To date, few studies have compared these two approaches in individuals with Parkinson disease or addressed some of the psychometric issues inherent when comparing these approaches to each other [6,7].

    Historically, the cognitive sequelae of Parkinson’s disease have been linked to deficits in executive function (e.g., planning, inhibition, problem solving), processing speed, and working memory and attributed to dopaminergic depletion in fronto-striatal networks [8,9]. Even so, various studies have found 3x error m_ci null prevalent, 3x error m_ci null, yet still pronounced, deficits in other cognitive domains such as memory [10,11], visuospatial skills [12,13], and semantic language function [14]. These varying cognitive sequelae of PD play out in both data-driven and classification approaches. Use of data-driven approaches (e.g., cluster analyses) has resulted in some variability in the patterns of PD cognitive phenotypes across studies. Some reveal phenotypes that primarily differ in the level and breadth of cognitive impairments [15,16,17]. Yet, other studies identify clusters that differ in the “types” of cognitive domains that are impaired [18,19,20]. For example, Crowley and colleagues [21], in a recent cluster analytic study, with prospectively recruited individuals with PD, identified three cognitive phenotypes—those showing low executive function, those with low episodic memory performance, 3x error m_ci null, and those with no deficits relative to age matched controls.

    There is also variability in the rules of the road used by various a priori classification approaches for identifying “mild cognitive impairment” in individuals with PD [22]. Most MCI classification approaches differ in terms of stringency of psychometric criteria such as number of cognitive tests used, use of composite scores, and impairment cutoff criteria. In 2012, the Movement Disorders Society (MDS) published consensus criteria for PD-MCI [23]. The Level II “comprehensive” criteria, which requires more extensive neuropsychological testing beyond a cognitive screener, defined impairment as having two or more tests falling 1–2 standard deviations (SD) below the normative mean or demonstrating a relative decline from previous evaluation [23]. While a diagnosis of PD-MCI using the MDS criteria is associated with greater risk of developing PDD [24], even with unified criteria, the prevalence rates of PD-MCI continue to range from 25–65% across studies [25,26]. Such disparate estimates of the portion of individuals with PD-MCI limits this diagnosis’ effectiveness at predicting clinical trajectory to dementia.

    In part, the variability in prevalence of PD-MCI across studies results from methodologic differences (i.e., community vs. clinical sample, sample sizes, which neuropsychological tests that are used). However, beyond that, the operationalization of impairment (e.g., use of −1, −1.5 or −2 SDs) is a critical issue. Moreover, variable use of 3x error m_ci null criteria relates to the notion of “decline” from a previous level, but this hinges on the assumption that test “norms” are inadequate to capture change in certain demographic sectors. Currently, results remain mixed over which cutoff criteria best identifies who is at greatest risk for impending dementia [8,24,27]. Previous work comparing empirical approaches to a PD-MCI classification, based on a prespecified impairment cutoff (−1.5 SD), found greater portions of PD-MCI participants in the more broadly impaired or amnestic phenotypes [6,7].

    The overall goal of the present study was to address the 3x error m_ci null of “cutoff” criteria head on by comparing clinical classification and data-driven approaches in a large clinical sample of idiopathic PD patients without dementia. We specifically wanted to learn which cutoff was optimal for classifying individuals as PD-MCI. This is important as it works towards establishing more consistent prevalence rates of PD-MCI. To achieve this goal, the current study first examined the influence of using different SD impairment criteria on PD-MCI prevalence rates and subtypes. Next, we identified data-driven cognitive phenotypes using cluster analysis in this same clinical sample. Taken together, 3x error m_ci null, these two approaches enabled us to determine how well the PD-MCI classifications mapped onto 3x error m_ci null cluster-derived cognitive phenotypes using each of three common SD impairment cutoffs.

    Based on previous literature [28,29,30,31,32], we predicted that the following empirically based phenotypes would emerge from cluster analyses: 3x error m_ci null average cognition, isolated executive function impairment, and broader cognitive impairment across multiple domains, particularly executive function, memory, and visuospatial. We predicted that a greater proportion of the PD-MCI cases would be represented in the cluster with broad cognitive impairment due to involvement of cortical systems underlying lower memory, visuospatial, and executive performance, 3x error m_ci null. Impairments in these domains have previously been shown to put individuals with PD at greater risk of developing PDD [33,34,35]. Finally, we planned to determine which impairment cutoff jointly maximized the model’s sensitivity and specificity and produced the highest classification accuracy.

    2. Materials and Methods

    2.1. Design

    We performed a cross-sectional, observation study by conducting a retrospective chart review of individuals with PD seen at the University of Florida (UF) Health Norman Fixel Institute for Neurological Diseases. Data encompassed participants’ demographics, disease-related characteristics, neuropsychological assessment, and mood/motivation screening measures.

    2.2. Participants

    Participants included a convenience sample of individuals with idiopathic PD from a large IRB-approved prospectively acquired clinical-research database (INFORM) of movement disorders patients seen at the UF Norman Fixel Institute. For the current study, inclusion criteria were: (1) evaluation between 2002 and 2019 and (2) a diagnosis of idiopathic PD made by a fellowship-trained movement disorders specialist based on the UK Parkinson’s Disease Society Brain Bank Diagnostic Criteria. Exclusion criteria entailed (a) any current major psychiatric disturbance (i.e., unmanaged bipolar disorder, schizophrenia, current episode; n = 7); (b) a comorbid essential tremor diagnosis (n = 13); (c) previous brain surgery (e.g., 3x error m_ci null, deep brain stimulation, pallidotomy; n = 87); (d) history of epilepsy, stroke, or brain injury with ongoing cognitive sequela (n = 18); (e) missing neuropsychological measures utilized in the study (n = 187); (f) evidence of significant cognitive impairment based on scores below 125 on the Dementia Rating Scale-2 (DRS-2, n = 127) [36], a cutoff which corresponds to ≤10th percentile 3x error m_ci null. After excluding (n 3x error m_ci null 439) participants from the starting sample (n = 933), this resulted in a final N of 494 participants for the current study.

    2.3. Neuropsychological Measures

    All participants received a comprehensive neuropsychological assessment. The battery consisted of the DRS-2 (as a general index of cognitive impairment) and standard neurocognitive measures in the domains of (1) executive function, (2) verbal delayed memory, (3) language, (4) visuospatial skills, and (5) attention/working memory. Specific tests are shown in Table 1, and cognitive measures are grouped by domain based on theoretical considerations [38,39,40]. Norms for each test were derived from test-specific manuals or previously published norms [41] and then converted to z-scores. Using normative data allowed us to compare performance to that expected in the population and more closely reflected clinical practice. However, this approach did present the limitation that measures were normed based on different samples and did not all adjust for additional demographics, such as education.

    Table 1

    Neuropsychological Tests within Each Cognitive Domain Composite.

    Cognitive DomainTestsRaw Score Used
    Executive FunctioningStroop Test (Interference trial)
    TMT Part B
    Letter Fluency (FAS)
    Total Number of Correct Items
    Completion Time
    Total Number of Words (all 3 trials)
    Verbal Delayed MemoryHVLT-R
    WMS-III Logical Memory
    Delayed Total Recall
    Delayed Total Recall
    LanguageBNT
    Semantic Fluency (Animals) *
    Total Correct Spontaneous Responses
    Total Number of Words
    Visuospatial SkillsBenton JOLO
    Benton FRT
    Total Items Correct
    Total Items Correct
    Attention/Working MemoryWAIS-III Digit Span Forward
    WAIS-III Digit Span Backward
    Total Number of Points
    Total Number of Points

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    For the majority of cognitive measures, less than 6% of the available sample had missing data. Only the measures included in the visuospatial composite contained a 3x error m_ci null portion of missing data (Judgment of Line Orientation: 8.08%, Benton Facial Recognition Test 14.41%), 3x error m_ci null. However, when analyzing the pattern of missing values for all cognitive measures, 3x error m_ci null, Little’s Missing Completely at Random (MCAR) assumption was supported (χ2(304) = 324.61, p = 0.20). Because participants needed at least two measures per domain for PD-MCI classification, listwise exclusion (if missing any neuropsychological data) was implemented.

    2.4. PD-MCI Classification

    We classified participants as cognitively normal or meeting actuarial criteria for PD-MCI using three commonly used impairment cutoffs: liberal (−1 SD), midpoint (−1.5 SD), and conservative (−2 SD). For a cognitive domain to be considered impaired, the normative scores on at least two tests within that domain had to fall below the respective cutoff (i.e., −1, −1.5, −2.0 SD). Having at least one impaired domain led to a classification of PD-MCI. This differs from the MDS criteria which allow PD-MCI to be defined by having one impaired test across two separate domains, with the implication that both of those domains are considered impaired. We took a more psychometrically rigorous approach by requiring two or more tests within the same domain to fall below the respective cutoff to assign a classification of PD-MCI. Indeed, this approach is more predictive of PDD [27], minimizes the possibility that poor performance on a single task is an anomaly, and aligns more closely with widespread clinical practice of defining domain impairment based a pattern of deficits across measures within a domain.

    Participants designated as having PD-MCI were then divided into subtypes based on whether they were impaired on one or multiple cognitive domains and whether executive function (EF) impairment was present or not. Just as the originally proposed MCI subtypes (amnestic/non-amnestic) aimed to distinguish the presence of or absence of the hallmark characteristic of Alzheimer’s disease [54], we focused on the presence or absence of the most common cognitive impairment (i.e., executive function) in PD. Thus, PD-MCI participants were characterized as being one of four subtypes: single-EF (only EF domain impaired), multi-EF (EF plus at least one other domain impaired), 3x error m_ci null, single-non-EF (one domain impaired but not EF), and multi-non-EF (more than one domain impaired but not EF).

    2.5. Cluster Analyses

    For each cognitive domain, a composite 3x error m_ci null was computed by averaging individual z-scores of tests within a domain. The five domain composite scores were then entered into the cluster analyses to distinguish cognitive phenotypes (groups of participants with similar patterns of cognitive performance). For the current manuscript, we refer to these cluster-derived subtypes as “cognitive phenotypes” to distinguish them from the 3x error m_ci null derived from the PD-MCI classification. While we had an a priori prediction of three clusters, we tried a range of two to four clusters to ensure ideal data fit; several cluster solutions were generated and contrasted before determining the final cluster structure.

    2.6. Other Measures

    At the time of the neuropsychological evaluation, error load failed acadapq completed self-report screening measures to characterize symptoms of depression (Beck Depression Inventory-II (BDI-II)), apathy (Apathy Scale (AS)), and situational and dispositional anxiety (State-Trait Anxiety Inventory (STAI)) [55,56,57]. To gauge motor symptom severity and disease stage progression, ratings from the Unified Parkinson’s Disease Rating Scale (UPDRS, 3x error m_ci null, [58]) Part III and the Hoehn and Yahr scale (H&Y, [59]) were obtained by movement disorder neurologists while participants were “on” their dopaminergic medications. These neurologists also characterized their motor subtype (tremor predominant, akinetic-rigid, or postural instability and gait difficulty). On average, 3x error m_ci null, motor symptoms were assessed within 61.33 ± 63.24 days of the neuropsychological evaluation (range = 0–365 days).

    2.7. Statistics

    We used SPSS Version 26 to conduct all the following analyses [60], 3x error m_ci null. We examined demographic variables, clinical characteristics, and cognitive composites for normality and outliers, both visually and statistically. Most variables were not normally distributed—as assessed by histogram inspection, Z-tests of skewness/kurtosis, and Kolmogorov–Smirnov and Shapiro–Wilk normality tests (p’s < 0.05). Due to the non-normality of most variables, outliers were defined as scores falling outside 3x the interquartile range. No outliers were detected except for one participant having more years with PD symptoms (54 years) and another having severe depression (BDI = 54). As these two variables were supplementary to our primary aims, all cases were retained within analyses.

    Cochran’s Q test compared the PD-MCI prevalence rates using Bonferroni-corrected pairwise comparisons. We independently conducted K-means and Hierarchical cluster analyses (using Ward’s method and squared Euclidean distance) to cross-validate 3x error m_ci null cluster memberships. To examine the consensus of the two techniques’ cluster memberships, we used cross-tabulations and Pearson chi-square tests of independence.

    Using the optimal K-means cluster solution, we compared the derived clusters on demographics, 3x error m_ci null, clinical characteristics, and mood/motivation. Due to the clinical nature of our data, some measures were missing, so we used pairwise exclusion for these analyses. Because of the non-normal distribution of these variables, when comparing clusters, we used Kruskal–Wallis H tests (with Bonferroni-corrected pairwise comparisons) for continuous variables and Pearson chi-square tests of independence for categorical variables.

    Finally, to quantify the relationship between cluster membership and PD-MCI classification, we used Pearson chi-square tests of independence and binary logistic regressions. Because we aimed to examine the overlap between the prominently impaired cluster and PD-MCI classification, this cluster was used as the reference group in the regression models, 3x error m_ci null. Using the models’ sensitivity and specificity, we calculated Youden’s Index values for each cutoff [61]. We then calculated positive and negative predictive values assuming base rates based on the sample’s prevalence rates of PD-MCI and across the range of prevalence rates from previous studies.

    3. Results

    3.1. Sample Characteristics

    The database search identified 494 individuals meeting inclusion/exclusion criteria. Of these, 338 individuals had neuropsychological assessments performed as part of an evaluation for deep brain stimulation, and 156 individuals had cognitive testing as part of routine clinical care. These groups were largely similar in terms of cognitive performance (see Appendix A Table A1) and thus were treated as a single cohort for the analyses. Participants ranged in age from 38 to 87 years old, with an average age of 64.7 years (Table 2). Participants were well-educated, predominantly male (72%), and white non-Hispanic (94.3%), and had an almost 8-year duration of a PD diagnosis on average. Participants were generally in the early-mid stages of disease severity based the H&Y and the UPDRS Part III. The majority were characterized as the tremor predominant subtype (76.5%), while the rest of the sample were characterized as akinetic-rigid (22.5%) or postural instability and gait difficulty (1.1%). As a group, participants’ DRS-2 total scores were far above the dementia cutoff [37], 3x error m_ci null. The average performance on indices of depression (BDI-II), apathy (AS), 3x error m_ci null, and anxiety (STAI) was below clinical cutoff, though there was substantial variability across participants.

    Table 2

    Sample Descriptive Characteristics.

    MeasureOverall Sample (n = 494)
    VariableMean/% (SD)
    Age64.73 (9.04)
    Education (years)15.01 (2.79)
    % Male72%
    % White, non-Hispanic94%
    Years since diagnosis7.84 (4.94)
    Years since symptom onset9.61 (5.26)
    PD motor subtype
    Tremor predominant77%
    Akinetic-rigid22%
    PIGD1%
    UPDRS III, on medication25.28 (9.80)
    Hoehn and Yahr (H-Y) Scale ^
    00.30%
    11%
    1.51%
    258%
    2.521%
    315%
    43%
    BDI-II, raw total10.10 (6.86)
    STAI: State anxiety, percentile61.33 (29.87)
    STAI: Trait anxiety, percentile58.38 (30.73)
    Apathy scale, raw total11.22 (6.31)
    Dementia Rating Scale-2, raw total136.99 (4.49)
    Cognitive composites (z-scores) #
    3x error m_ci null colspan="1">Executive function−0.58 (0.90)
    Verbal delayed memory−0.36 (1.01)
    Language−0.03 (0.96)
    Visuospatial abilities0.01 (0.78)
    Attention/working memory0.18 (0.77)

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    3.2. Prevalence of PD-MCI and Subtypes

    The prevalence of PD-MCI was 40.1% (n = 198) when using −1 SD cutoff, 21.5% 3x error m_ci null = 105) when using the −1.5 cutoff, and 9.1% (n = 45) when using the −2 SD cutoff. There was a significant difference between the proportions of PD-MCI classified cases based on cutoff criteria, with a large effect size (χ2(2) = 563.10, p < 0.001, η2 = 0.66) and differences in the expected direction (p’s < 0.001).

    Across all three cutoffs, most PD-MCI cases had single-domain impairments (−1 SD: 64.59%, −1.5 SD: 77.0%, −2 SD: 80.22%) (Figure 1). Single-EF was the most common PD-MCI subtype. However, a notable portion of cases fell into non-EF subtypes (−1 SD: 19%, −1.5 SD: 19%, −2 SD: 26%). Classification into these 1c8.2 cant start driver - error 2 subtypes was primarily driven by memory and language deficits. Of the PD-MCI cases, when using the −1, bdm100 + 12vcc power error, and −2 SD cutoffs, 33%, 25%, and 31% had memory deficits, and 17%, 15%, and 11% had language deficits, respectively.

    3.3. Cluster-Derived Cognitive Phenotypes

    Results of the K-means cluster analysis supported the existence of three clusters. Cluster membership was stable after 10 iterations. None of the clusters were unacceptably small, 3x error m_ci null. Visual inspection of the cluster centers (Figure 2) revealed a group with average cognition across all domains (n = 154), a group with low executive function (Low EF) (n = 227), and a group with executive function and memory impairments, as well as low language scores (Prominently Impaired EF/Memory) (n = 113).

    The hierarchical cluster analysis supported the use of two or three clusters based on the changes in agglomeration coefficients. When examining the proportions of cases assigned to the same cluster by both clustering methods, the three-cluster solution had highest agreement (84.41%), relative to the two and four cluster solutions (78.34%, 58.70%, respectively), and far exceeded the 25% greater than chance threshold. Using K-means as the standard, there was agreement on 89.61% (n = 138) of the Cognitively Average group, 83.36% (n = 3x error m_ci null of the Low EF group, and 79.67% (n = 90) of the Prominently Impaired EF/Memory group. There was a significant relationship between the likelihood of being assigned to the equivalent group using both clustering methods (χ2(4) = 598.73, p < 0.001). Thus, the three K-means clusters were determined to be the optimal cluster solution and were used in all subsequent analyses.

    Table 3 depicts the demographic, cognitive, mood, and motor scores of the three cognitive clusters. Results of Kruskal–Wallis H tests indicated that the three clusters significantly differed across DRS-2 total scores and all cognitive composite scores in the expected direction. Specifically, participants in the Cognitively Average group performed better than those in the Low EF group, tooltip as error mfc performed better than those in the Prominently Impaired EF/Memory group across all cognitive indices.

    Table 3

    Comparing the K-means Clusters’ Descriptive, Clinical, and Cognitive Characteristics.

    Characteristic
    Measure
    Cluster 1
    Cognitively Average
    3x error m_ci null 2
    Low EF
    Cluster 3
    Prominently Impaired EF/Memory
    Omnibus Kruskal–
    Wallis
    H-Test
    Effect SizePost hoc
    Differences (Bonferroni Corrected)
    N = 1543x error m_ci null colspan="1">N = 227N = 113
    Mean (SD)/Mean (SD)/Mean (SD)/p-valueEta squared /Cramer’s V #
    %%%
    Age (years)64.51 (8.75)65.31 (9.12)63.85 (9.15)0.380.004--
    Education (years)15.35 (2.55)14.91 (2.91)14.73 (2.83)0.130.01--
    Sex (% Male)68%73%75%0.33 ^0.07 #--
    % Caucasian, Non99%93%91%0.01 ^0.15 #1 < [2 = 3] *
    Hispanic
    % Error loading verification executable Stages 2–395%93%95%0.57 ^0.06 #-
    % Tremor Subtype73%76%82%0.16 ^0.08 #--
    Years Since Symptom9.45 (5.14)9.51 (5.20)10.03 (5.57)0.580.002--
    Onset
    Years Since Diagnosis7.70 (5.06)7.58 (4.73)8.56 (5.15)0.230.01--
    UPDRS Part III22.78 (8.85)25.18 (9.38)28.91 (10.81)<0.0010.05[1 = 2] < 3 **
    BDI-II9.15 (7.04)9.81 (6.06)12.09 (7.79)0.0010.031 < 3 **
    Apathy Scale10.47 (6.33)10.89 (6.25)13.01 (6.14)0.010.02[1 = 2] < 3 **
    STAI: State Pct.53.20 (31.34)63.26 (28.51)68.73 (28.09)<0.0010.041 < [2 = 3] **
    STAI: Trait Pct.50.11 (31.29)59.21 (30.30)68.33 (27.73)<0.0010.041 < 2 < 3 **
    DRS-23x error m_ci null (3.10)136.92 (4.22)133.65 (4.42)<0.0010.231 > 2 > 3 *
    Cognitive Domain
    Z-Score Composites
    Executive Function0.20 (0.59)−0.58 (0.58)−1.63 (0.65)<0.0010.561 3x error m_ci null 2 > 3 *
    Memory0.51 (0.70)−0.44 (0.75)−1.40 (0.75)<0.0010.471 > 2 > 3 *
    Language0.79 (0.68)−0.08 (0.70)−1.02 (0.72)<0.0010.481 > 2 > 3 *
    Visuospatial Skills0.44 (0.56)0.01 (0.70)−0.59 (0.82)<0.0010.211 > 2 > 3 *
    Attention/WM0.67 (0.70)0.03 (0.72)−0.20 (0.63)<0.001 0.201 > 2 > 3 **

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    As shown in Table 3, the three clusters also differed with respect to motor symptom severity, self-reported mood symptoms, and racial/ethnic distribution. Namely, participants in the Prominently Impaired EF/Memory cluster had significantly greater motor symptoms (UPDRS Part III scores), greater apathy (AS), and greater trait anxiety (STAI: Trait) than both other clusters and greater depressive symptoms (BDI-II) than the Cognitively Average cluster. Those in the Low EF and Prominently Impaired EF/Memory clusters had significantly greater state anxiety (STAI: State) than the Cognitively Average cluster. Moreover, there was a significant difference between the clusters’ proportions of white non-Hispanic participants, with a fewer represented in the Cognitively Average cluster relative to both other clusters. In contrast, there were no significant differences among the clusters across other demographic characteristics (age, education, sex), duration of illness (years since diagnosis, years since symptom onset), or proportion of participants with each motor subtype. Overall, the Prominently Impaired EF/Memory cluster had significantly worse mood, motivation, and motor symptoms than the other two clusters, but the effect sizes of these differences were small. As a follow-up, we conducted Pearson correlation analyses between the cognitive composites and mood/motivation measures (See Table A2 for analyses). Overall, the results continued to suggest an exceptionally small but consistent relationship between greater mood symptoms and worse cognitive performance across domains. Additionally, we conducted exploratory analyses within the language domain to determine whether one of the two measures drove the low language performance seen within the Prominently Impaired EF/ Memory cluster. We found that semantic fluency performance was significantly lower than confrontation naming (see Table A3).

    3.4. Relationship between Cognitive Phenotypes and PD-MCI Classification

    Table 4 depicts the distribution of PD-MCI cases within each cluster using the three PD-MCI impairment cutoffs. Pearson chi-square tests of independence revealed that PD-MCI classification and cluster membership were significantly related to one another with a large effect size (Table 4). Across all three cutoffs, the Cognitively Average cluster contained very few PD-MCI cases. Using the −1 SD cutoff, 3x error m_ci null, the Low EF and Prominently Impaired EF/Memory clusters contained similar portions of the PD-MCI cases. Using the −1.5 SD cutoff, about three quarters of the PD-MCI cases fell into the Prominently Impaired EF/Memory cluster while about a quarter fell into the Low EF cluster. Finally, 3x error m_ci null, using the −2 SD cutoff, almost all the PD-MCI cases fell into the Prominently Impaired EF/Memory cluster. Thus, the more stringent the impairment cutoff, the more sensitive the Prominently Impaired EF/Memory cluster was to containing greater portions of the PD-MCI classified cases.

    Table 4

    Percentage of PD-MCI Cases Falling to Each K-Means Cluster.

    Impairment CutoffCognitively
    Average
    % (n)
    Low EF
    % (n)
    Prominently Impaired EF/Memory
    % (n)
    Pearson Chi Square p-ValueCramer’s V
    −1 SD1.01% (2)46.46% (92)52.53% (194)223.47<0.0010.67
    −1.5 SD0.95% (1)3x error m_ci null colspan="1">23.81% (25)75.24% (79)213.13<0.0010.66
    −2 SD0% (0)4.44% (2)95.56% (43)148.33<0.0010.55

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    Binary logistic regression analyses examined how well cluster membership predicted PD-MCI classification. Each impairment 3x error m_ci null had significant omnibus tests (−1 SD: X2(2) = 274.61, p < 0.001, Cox and Snell R2 = 0.43, 3x error m_ci null, Nagelkerke R2 = 0.58; −1.5 SD: X2(2) = 203.37, p < 0.001, Cox and Snell R2 = 0.34, Nagelkerke R2 = 0.52; −2 SD: X2(2) = 128.35, p < 0.001, Cox and Snell R2 = 0.23, Nagelkerke R2 = 0.50). The models all had large effect sizes, explaining between 50–58% of the variance in PD-MCI classification, and cluster membership was a significant predictor in all three impairment cutoff models.

    Using the −1 SD cutoff, those in the Cognitively Average cluster had 1000× lower odds of being classified as PD-MCI, relative to the Prominently Impaired EF/Memory cluster, while those in the Low EF cluster had 16.95× lower odds (p’s < 0.001; Cognitively Average cluster’s 95% Confidence Interval (CI): 200-perfect 3x error m_ci null fit; Low EF’s 95% CI: 8.29–35.71). This model correctly classified 79.1% of PD-MCI cases with poor sensitivity (as only about half of PD-MCI cases were classified as such by the model) and excellent specificity (as almost all Cognitively Average cluster participants were correctly classified as cognitively normal by the model; Table 5). Using the −1.5 SD cutoff, those in the Cognitively Average 3x error m_ci null had 333.33× lower odds of being classified as PD-MCI, relative to the Prominently Impaired EF/Memory cluster, while those in the Low EF cluster had 18.87× lower odds (p’s < 0.001; Cognitively Average’s 95% CI: 47.62-perfect model fit; Low EF’s 95% CI: 10.53–33.33). This model correctly classified 87.9% of PD-MCI cases with stronger sensitivity and slightly lower (but still excellent) specificity than the −1 SD criteria model. Finally, using the −2 SD cutoff, those in the Low EF cluster had 71.43x lower odds of being classified as PD-MCI, 3x error m_ci null, relative to the Prominently Impaired EF/Memory cluster, while no cases in the Cognitively Average cluster were classified as PD-MCI (Low EF p < 0.001, 95% CI: 16.39–333.33). This final model correctly classified 90.9% of PD-MCI cases, but the model predicted that all cases were cognitively normal, leading to a null sensitivity and perfect specificity.

    Table 5

    Binary logistic regression models’ sensitivity, specificity, and positive and negative predictive values based on different PD-MCI prevalence rates.

    Impairment CutoffSensitivitySpecificityC Stat.Sample0.25Base Rate
    0.45
    0.65
    PPV NPVPPV NPVPPV NPVPPV NPV
    −1 SD0.530.970.860.920.760.850.863x error m_ci null rowspan="1" colspan="1">0.720.970.53
    −1.5 SD0.750.910.880.700.930.740.920.870.820.940.66
    −2 SD0.001.000.91--0.91--0.75--0.55--0.35

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    When using the models’ predicted PD-MCI group membership to predict actual PD-MCI classification, all three models produce significant, acceptable C statistics (above 70%, p’s < 0.001; Table 5). The model using the −1.5 SD cutoff had the highest jointly maximized sensitivity and specificity (−1 SD Youden’s Index (YI): 0.50; −1.5 SD YI: 0.66; −2 SD YI: 0). Table 5 presents the positive and negative predictive values predicated on a range of PD-MCI base rate estimates, 3x error m_ci null. Using the sample’s prevalence rates for each cutoff, the −1 SD cutoff maximizes the probability that those classified by the model as PD-MCI truly meet this actuarial diagnosis while the −1.5 SD cutoff maximizes the probability that those classified as cognitively normal are truly cognitively intact. Since the true base rate of PD-MCI is unknown, the low, midpoint, and high end of the range of estimated prevalence rates were also used to calculate positive and negative predictive values [25,26], 3x error m_ci null. In settings with lower PD-MCI prevalence rates (e.g., 25%), using −1 SD would jointly maximize the probability of correct classification, but in settings containing a population with greater chance of impairment (e.g., 45%), then −1.5 SD would do so. As our patients 3x error m_ci null all seen in a specialty clinic, 3x error m_ci null, the prevalence of PD-MCI in our sample is presumably closer to this midpoint of the prevalence rates previously estimated. Taken all together, using the −1.5 SD cutoff resulted in cluster membership having high model-based classification accuracy, the largest YI, and jointly maximized PPV/NPV (based on our sample’s clinical setting).

    4. Discussion

    Our study investigated different techniques of methodologically defining and characterizing cognitive impairment in a large, clinical sample of individuals with idiopathic PD without dementia. We took two 3x error m_ci null (i.e., actuarial PD-MCI classification, cluster analytic) and looked at their overlap. In doing so, 3x error m_ci null, we hoped to learn which cognitive phenotypes empirically 3x error m_ci null, the influence of different impairment cutoffs on PD-MCI prevalence rates, and whether a specific impairment cutoff aligned best with the cognitive phenotype reflecting greater PDD risk.

    The actuarially defined PD-MCI prevalence varied from 40.1% using the liberal end of impairment criteria (−1 SD), to 21.5% using the midpoint (−1.5 SD), and 9.1% using the conservative end (−2 SD). Regardless of impairment cutoff, most PD-MCI cases involved single-domain impairment. This finding aligns with that of Marras windows xp error colleagues [62] and runs counter to that of others who describe PD-MCI as most commonly involving multi-domain impairment [25,62,63]. This discrepancy likely reflects methodological differences. For example, if one strictly follows proposed criteria for MCI by the Movement Disorder Society (MDS) [23], then having a single impaired test across two separate domains leads to the designation of multi-domain PD-MCI. In contrast, other more psychometrically rigorous approaches require participants to have at least two impaired measures within a domain for it to be considered impaired, 3x error m_ci null. Marras and colleagues [62] found that when strictly using MDS criteria, most PD-MCI cases demonstrated multi-domain impairment; however, when they analyzed the same sample with an altered operationalization of impairment that required two impaired tests within a domain, the majority of PD-MCI cases had single domain impairment. Thus, using a similarly more stringent operationalization of impairment, 3x error m_ci null, our results support the commonality of the single-domain impairment in a larger sample of individuals with PD without dementia.

    In the current study, we grouped those classified as PD-MCI into executive vs. nonexecutive subtypes, with presence or absence of other co-occurring cognitive difficulties (e.g., EF—single domain, EF—multi-domain). This method of subtyping allowed us to distinguish the variety of cognitive domains impaired beyond executive dysfunction. Using this approach, we found, across all three cutoffs, the Single-EF subtype was the most prevalent, but 19–26% of PD-MCI cases (depending on the cutoff) exhibited impairments only in other domains-reinforcing the existence of variable patterns in cognitive performance across individuals with PD. Beyond the most prevalent deficit, executive dysfunction, participants primarily demonstrated deficits in memory and language domains.

    Using a different statistical approach (cluster analysis), we found three distinct cognitive phenotypes in this same sample of individuals with PD. These phenotypes differed in severity of cognitive deficits: (1) average cognition, (2) low EF, and (3) more prominent impairments in EF and memory with low language abilities. Though this is a cross-sectional study, it is possible that these phenotypes may reflect the succession of neuropathological changes. Namely, individuals with PD develop frontal executive dysfunction based on dopaminergic changes in frontal-striatal networks and, as the disease progresses, more cortical system and limbic deficits develop (based on cholinergic changes) [29,30,31]. With disease progression, individuals with greater cognitive deficits may have more widespread involvement of cortical areas which likely increases their risk of transitioning to PDD. This notion was recently supported by Domellöf and colleagues [64] who found that significantly lower performance on semantic fluency, memory, and EF measures, identified individuals with PD-MCI 3x error m_ci null converted to PDD over a five-year period. Thus, our broadly impaired cluster contained multiple deficits previously shown to be predictive of progression to PDD.

    Participants in the more prominently impaired cluster demonstrated worse motor symptoms (UPDRS-Part III scores) than the other two clusters. This finding is in alignment with previous research showing greater cognitive dysfunction (including dementia risk) in those with more advanced motor symptoms and disease progression [65,66,67]. The prominently impaired socket error 10013 access denied mailwasher also had greater mood symptoms relative to the other two clusters. While the influence of mood is likely a contributing component to their performance, the cluster differences had small effect sizes, suggesting a minimal impact of mood on cluster membership. We did not find broad evidence for demographic differences between the three clusters, a finding that conflicts with prior research that older age, less education, and longer disease duration are associated with worse cognition [68,69,70]. Of note, the cognitive clusters were based on composite scores of “normed” neuropsychological measures, which controls for certain demographic factors. As such, the norming might obfuscate findings of age, and potentially education, differences across the cluster phenotypes. We error 50040 activation find that the cognitively average cluster had a greater proportion of white non-Hispanic participants; however, the small sample sizes of other races/ethnicities in the overall sample limit our ability to draw related inferences.

    Finally, the outcomes of the data-driven and theoretical approaches were compared. We found that the midpoint cutoff (−1.5 SD) served as the best predictor of PD-MCI classification relative to the other cutoffs in terms of classification accuracy and jointly maximized sensitivity and specificity of the model. Use of the midpoint (−1.5) cutoff resulted in three-fourths of the PD-MCI cases falling into the prominently impaired cluster, whereas use of liberal (−1 SD) cutoff resulted equivalent distribution of PD-MCI cases into the low EF and prominently impaired clusters. Researchers previously tried to validate the same three PD-MCI impairment cutoffs by comparing them against clinical diagnosis, but findings have been inconsistent, supporting cutoffs at either −1.5 SD [71] or −2 SD [8], 3x error m_ci null. Furthermore, these clinical validation methods use a circular logic in that clinical diagnosis of impairment would still require a preconceived understanding of what performance counts as impaired relative to a normative expectation. Comparing actuarial and empirical approaches serves as a validation method that circumvents this circular logic, 3x error m_ci null. This methodology has precedence within the Alzheimer’s literature which found that data-driven approaches may enhance sensitivity for detecting both cross-sectional and future clinical, biomarker, and neuropathological outcomes-a topic that should fatal error c1902 cygwin explored in future work with PD participants.

    Past longitudinal work evaluating which dj skinhead - extreme terror download cutoff best predicts PDD development over a multi-year follow-up period also remains mixed-with some studies supporting an optimal cutoff at −1.5 SD [27] while others support a cutoff of −2 SD [72]. Though cross-sectional, our findings further support the use of a midpoint (−1.5 SD) cutoff based on its validation against the sample’s cognitive phenotype with deficits that past studies suggest are 3x error m_ci null of PDD.

    This study has limitations. First, our clinical sample may not be representative of a broader population of individuals with PD as our data were collected at a specialty center from a combination of patients seeking deep brain stimulation and those referred for a neuropsychological evaluation due to cognitive concerns. Second, while patients were clinically diagnosed with PD using established clinical criteria, this patient population did not have pathologically confirmed PD (to definitively rule out other syndromes that could mirror PD early on, such as Progressive Supranuclear Palsy-Parkinsonism Predominant variant). Third, we did not have access to the whole sample’s medication information that would enable us to characterize the potential relationship of cognitive performance with medications (e.g., parkinsonian medication’s LEDD values, or rate of anticholinergic use). A small subset of recently seen patients (n = 20/cluster) had available medication lists, from which Magellan Anticholinergic Risk Scale scores were calculated [73]. A chi-square test of independence showed no significant differences in the proportions of Magellan scores across clusters and weak effect size (p = 0.516, 3x error m_ci null, Cramer’s V = 0.20), suggesting that our predominantly impaired group did not have a significantly disproportionate amount of participants on anticholinergic medication. Fourth, we used listwise exclusion to meet the goal that all participants have two or more measures within each domain to classify them as PD-MCI. There is a possibility that we may have missed more severely impaired individuals who did not complete the full battery of 3x error m_ci null, though these individuals would have likely been excluded based on our cognitive screener.

    More broadly, there are some issues involving current practices used for formal clinical diagnosis of MCI. One practice is 3x error m_ci null requirement that patients have subjective cognitive complaints in order to receive MCI diagnosis (as in the MDS PD-MCI consensus criteria), 3x error m_ci null. We did not have this information readily available, and not applying this broadly used MDS criteria limits the comparability of our findings to other studies that use it. Even so, there is precedence for not including subjective cognitive complaints within an actuarial version of the PD-MCI criteria [7,74,75,76], and evidence for the grub error 18 of this criteria is mixed [77,78]. Finally, clinicians often make a diagnosis of MCI in situations where there has been a performance drop from an estimated premorbid baseline (e.g., a, drop from superior to low average ranges). We were unable to account for impairment based on decline from premorbid abilities in this sample. However, defining MCI with actuarial methods has gained traction within the Alzheimer’s literature and been shown to improve diagnostic rigor for MCI [22,79,80,81]. Thus, further research examining actuarial methods to characterize PD-MCI may prove helpful in establishing a “gold standard” and “true” prevalence rates.

    Future work should expand to a more racially/ethnically diverse sample with wider levels of educational attainment to better generalize the results to a broader patient population. It would also be helpful to conduct a longitudinal study to evaluate which impairment cutoff best predicts PDD development in a larger sample than previous studies.

    5. Conclusions

    The current findings add to the literature by demonstrating the utility of comparing empirical and classification definitions of cognitive impairment. Our results reinforce that variability in prevalence rates of actuarially-defined PD-MCI stems, in part, from use of different normative definitions of impairment (e.g., −1 to −2 SD). Although this may seem trivial, it dramatically affects prevalence rates and in turn influences predictive validity of dementia. Yet, across all cutoffs, PD-MCI classified cases most commonly exhibited single-domain deficits (primarily in executive function). When empirically defining patterns of cognitive impairment in a large clinical sample, we found three distinct cognitive phenotypes with differing levels of cognitive deficit severity. The cognitive phenotype with broader, more prominent impairments (including features suggestive of greater risk of impending PDD development) best aligned with operationalizing impairment at the midpoint cutoff (−1.5 SD). These findings contribute to the widespread efforts to determine criteria that best establish what level and which patterns of cognitive impairment have the most utility at predicting who is at greatest risk of upcoming progression to PDD.

    Appendix A. Comparison of Deep Brain Stimulation and General Clinic Patients’ Cognitive Performance

    Table A1

    Cognitive performance of deep brain stimulation candidates versus xml parsing error error 108 unknown joomla clinic patients.

    MeasureDBSGeneral ClinicSignificance
    (n = 338)(n = 156)
    Mean (SD)Means (SD)p-value
    Dementia Rating Scale-2, 3x error m_ci null, raw total137.05 (4.28) 136.86 (4.92) 0.69
    Cognitive Composites (z-scores) #
    Executive Function−0.55 (0.88)−0.64 (0.93)0.32
    Verbal Delayed Memory−0.37 (1.00) −0.36 (1.04)0.95
    Language0.001 (0.94) −0.09 (1.00)0.35
    Visuospatial Abilities0.01 (0.78) 0.02 (0.79) 0.85
    Attention/Working Memory0.20 (0.77) 0.11 (0.76) 0.22

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    Appendix B. Relationship between Mood and Cognitive Domains

    Table A2

    Pearson correlations between mood measures and composite z-scores.

    MeasureExecutive FunctionVerbal
    Delayed Memory
    LanguageVisuospatialAttention/
    Working Memory
    BDI-II−0.10 *−0.13 *−0.09 *−0.10 *−0.16 *
    STAI
    State−0.18 *−0.10 *−0.18 *−0.10 *−0.08
    Trait−0.18 *−0.15 *−0.17 *−0.14 *−0.15 *
    Apathy Scale−0.14 *−0.10−0.09−0.13 *−0.09

    Open in a separate window

    Greater depressive symptoms (BDI-II) and dispositional anxiety (STAI-Trait) were both significantly associated with poorer performance across all composites, with 3x error m_ci null effect sizes. Greater situational anxiety (STAI-State) significantly related to worse performance on all composites except attention/working memory, with small effect sizes, and greater apathy symptoms (AS) significantly correlated with poorer performance on executive and visuospatial composites.

    Appendix C. Exploratory Analyses of Language Metrics

    Table A3

    Z-scores of Language Metrics across Clusters.

    MetricCognitively AverageLow EF Prominently Impaired EF/Memory
    Boston Naming Test1.05 (0.96)0.18 (1.01)−0.67 (0.96)
    Semantic Fluency (Animals)0.52 (0.90)−0.35 (0.96)−1.37 (1.04)

    Open in a separate window

    Table A3 shows mean scores of BNT and semantic fluency (Animals) across the 3 clusters. Results of a between (cluster) x within (language measure) repeated measures ANOVA revealed a significant main effect of language measures (F(1.00, 491.00) = 95.94, p < 0.001, np2 = 0.16) 3x error m_ci null semantic fluency was significantly lower than confrontation naming (M = −0.65, p < 0.001). The main effect of cluster was also significant (F(2, 433.61) = 202.84, p < 0.001), with the Cognitively Average cluster performing significantly better than the Low EF cluster (M difference = 0.87) who in turn scored better than the Prominently Impaired EF/Memory cluster (M difference = 0.78), with all p values < 0.001. The cluster x language measure interaction was nonsignificant (F(2.00, 491.00) = 0.50, p > 0.05, np2 = 0.002). Thus, all clusters demonstrated similar patterns of worse semantic fluency performance relative to confrontation naming.

    Author Contributions

    Conceptualization, L.E.K. and D.B.; Data curation, L.E.K.; Formal 3x error m_ci null, L.E.K., A.M.R. and F.V.L.; Funding acquisition, C.C.P. and D.B.; Methodology, L.E.K., C.C.P., M.J.A. and D.B.; Supervision, C.C.P., M.J.A. and D.B.; Visualization, L.E.K.; Writing—original draft, L.E.K.; Writing—review and editing, L.E.K., A.M.R., F.V.L., C.C.P. and M.J.A. and D.B. All authors have read and agreed to the published version of the manuscript.

    Funding

    This project was supported by the Norman Fixel Institute for Neurological Diseases and partially 3x error m_ci null by the National Institutes of Health (Grant number: T32-NS082168, Grant number: R01NS082386, Grant number: K07AG066813).

    Institutional Review Board Statement

    The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the University of Florida (protocol code 211701522 and date of approval 6/22/2017).

    Informed Consent Statement

    Informed consent was obtained from all subjects involved in the study.

    Data Availability Statement

    The datasets presented in this article are not publicly available because an inquiring party must submit a request to the UF INFORM database committee at the Norman Fixel Institute of Neurologic Diseases, and this request must be approved by the UF IRB. Requests to access the datasets should microsoft application error reporting directed to “Chuck Jacobson, [email protected]”.

    Conflicts of Interest

    The authors declare no conflict of interest with respect to this study.

    Footnotes

    Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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    In boarding the supervisor was offering passengers vouchers because weight restrictions. I couldn't take the morning flight because of the time wasn't suitable for me. I asked the supervisor to put me on a later flight out of JFK so I could leave now and catch that flight. She showed reluctance to do so. Clearly not the service delta wants to provide in this environment with delays.

    Delta does a great job. But im now looking for more direct flights in the future, 3x error m_ci null. My time is more valuable. I was in the airport/on a plane for 9 hours!

    The plane was ms access error 429 activex component new so did not yet have WiFi installed. Otherwise everything was great for the long flight from Tel Aviv to New York

    Timely boarding announcements, fairly roomy seating, and prompt snack delivery. Seats in the waiting area could have USB charging ports on both sides. Minor issue; I charged my phone on the flight.

    Seats were surprisingly comfortable and sufficiently roomy. Flight attendants were helpful and courteous. Flight departed on time and arrived a little early. My wife and I both agreed this may have been the best flight we've ever had: a direct flight from Kansas City to Atlanta to visit my son and his family. Convenient, relatively inexpensive, and overall a great experience!

    Pros: "Helpful and attentive crew"

    Pros: "Crew was super amazing and friendly! Very good service also!"

    Cons: "No seat back entertainment."

    Pros: "The best other than the fact it was packed full lol but that’s not Deltas fault"

    Pros: "The flight itself was excellent. Friendly, helpful, kind — great attendants and crew."

    Cons: "The flight was delayed 4 hours. We never found out why exactly. That was a little tough but staff was great"

    Pros: "We were in coach and the crew made us feel like it was business class!"

    Pros: "Boarding was very efficient. Flight attendants were helpful and kind and seemed to care."

    Cons: "We booked basic seats knowing we might not sit together however we bluesoleil error 1714 not know they would separate children. They put my husband and I in an exit row and my daughter at the back of the plane with strangers. I was not comfortable with strangers being responsible for my child, 3x error m_ci null. I assumed they would seat children with at least one parent. We did ask to move at the gate and the accommodated us with the last row on the plane, 3x error m_ci null. No recline, no window, and right next to the bathrooms, 3x error m_ci null. We took it to be with our kid but this policy needs to be revised. Kids should always be seated with the adult responsible for them. who knows what kind of person might end up next to my child. Not 3x error m_ci null mention if she had needed something is the stranger gonna take care of it? It’s just a bad practice imo."

    Pros: "Quick and easy boarding and departing. Wonderful and friendly staff."

    Cons: "Honestly, everything was great. Food and entertainment were a little lacking but for a 3 hour flight it was more than acceptable."

    Pros: "Great crew, prompt and courteous despite the short flight"

    Cons: "Flight departed an hour past scheduled time due to a snafu with flight attendants: they were either absent or really late or a replacement crew. Unacceptable personnel management."

    Pros: "Amazing crew"

    Pros: "The crew was polite and pleasant unlike the crew from KC to Boston."

    Cons: "Telling us to check bags before we get to our seat and find out there is no more room."

    Cons: "Just a bunch of weather delays because of the bad storms. I did not like the selection of movies and tv shows on the delta flight. So I just listened to podcast in my phone. But other than that everything was great."

    Pros: "Helpful crew."

    Cons: "These planes are tiny. Our equipment was B717."

    Pros: "Small plane without bells and whistles and no middle seats."

    Cons: "The internet would not work. I couldn’t use any of the inflight entertainment."

    Pros: "We had the worst flight ever on Delta flight worst Attitude of the flight attendant she was very Rude i even told her she was"

    Cons: "We didn't get served nothing to drink until 45 min to kc then by then i was so dehydrated i asked for a can of pop she said NO I SAID REALLY SHE SAID DELTAS NOT IN CHARGE OF STOCKING DRINKS & SNACKS SHE HAD MORE PEOPLE' TO SERVE REALLY EVERBODY IN FRONT OF US GOT WHAT THEY WANTED SO I HAD NOTHIN AT"

    Cons: "2nd Delta flight on the same day that was delayed. This one only 44 min."

    Pros: "Wonderful friendly batman arkham asylum securom 9000 error. Comfy seat. Very pleasantly impressed with the comfort on a CRJ900 -- windows are large and closer to eye level, standing room is enough."

    Cons: "Never made it because of my originating flight"

    Cons: "The airline cancelled the flight alluring weather conditions, when the reality was they did not wanted the plane to park in Kansas. The weather conditions were even worse on the flight I was moved to, and that flight was not cancelled. They absolutely did not care about the passengers"

    Pros: "Overall good experience"

    Cons: "Plane 1hr late taking off"

    Pros: "Nice people"

    Cons: "Waiting at gate in KC"

    Pros: "Efficient and friendly"

    Pros: "The movies kept my daughter busy."

    Pros: "Awesomeness"

    Pros: "Professional, courteous, and responsive attendants and flight crew."

    Cons: "Nothing."

    Pros: "I did not like anything all. 3x error m_ci null the to last agent to help me after I was send to different airlines"

    Cons: "And when I get to US delta Airline ticketr did not even look at my ticket she just send to Virginia Australia make me rotterdam terror corpse all over. I know it supposed to be delta"

    Pros: "The flight was nearly full, but I lucked out. One person in my row did not show up, so myself and the other lady in 3x error m_ci null row had the benefit of having an open seat in between us. The crew was cheerful and accommodating. They did the normal beverage service, but also brought complimentary water and coffee 3x during the rest of the flight. This was greatly appreciated, especially after 5 days of drinking and partying. My buddies and I spent two and a half days in Las Vegas for a bachelor party followed by two days in the LA area for a wedding (yes we did it Hangover style) :) Thank you Delta!"

    Cons: "My only complaint was that the flight was delayed out of LAX by about 30 minutes due to the flight in-bound being delayed. However, the captain made up most of this time in the air so it ended up being a non-issue."

    Cons: "We were on the tarmac for almost 2 hours. It's probably LaGuardia but the experience was very bad."

    Pros: "Made the best of a overcrowded messy airport"

    Pros: "Horrible seats. Scraped up my knees on a screwhead on the seat in front of me. Way too cramped."

    Pros: "Boarding was delayed, but flight crew & desk staff moved us quickly through & off we went. It was efficient & well managed."

    Cons: "A bit cramped on board. Thinking of the discount carriers while smooshed in with my aisle mates."

    Pros: "Big bathrooms, friendly staff, free eyemaks"

    Cons: "Delays. Ways late."

    Pros: 3x error m_ci null service and non stop smooth ride. Boarding was a new experiance taking a bus to the plane. Was quick and crew helpful storing my carryon. Everyone very helpful."

    Pros: "Love the free movies and individual screen, and the new seats are more comfortable"

    Cons: "That it wasn’t 1970, with full meals 3x error m_ci null more leg room"

    Cons: "Landing was frightening."

    Pros: "The quick flight was nice, the flight attendants were super sweet and kind and were willing to give me extra snacks when I requested for them. No screens on this flight, but understandable since it was such a short flight :)"

    Cons: "Nothing"

    Pros: "Other than the delay by the Hong Kong Airport controller, everything went smoothly. The plane was late to Seattle."

    Cons: "The luggage custom clearing would be much better if we could do it like the Vancouver BC where an electronic monitor was used to identify one's luggage without the need to handle them manually. Much more efficient and allowing folks to get on the connecting flights easier."

    Pros: "free texting and entertainment!"

    Cons: "our flight was delayed half an hour."

    Pros: "Crew and landing were fantastic"

    Pros: "Nothing."

    Cons: "Flight attendant late arriving to his job causing a 30 minute delay in boarding, 3x error m_ci null. Desk staff at airport seemed more interested in their own conversations than helping passengers. Fight attendants seemed uninterested in their jobs and lacked warmth. 45 minutes late arriving in Kansas City no announcements from captain"

    Pros: "The smootheness of the flight."

    Cons: "The fact that the passenger behind me is was kicking the back of my seat. And it wasn't even a child!"

    Pros: "The fact that there were no delays!"

    Cons: "Nothing"

    Pros: "In-flight entertainment (if you brought a tablet or laptop with you), 3x error m_ci null, yummy gluten free pretzels, good flight attendants."

    Cons: "A complimentary sandwich would have been nice for a 4 hour flight."

    Pros: "Flights were on time."

    Cons: "Worst seats ever. Uncomfortable. Didn't recline and were supposed to. Was told by the 3x error m_ci null "that's too bad. It's supposed to" when I mentioned it."

    Pros: "The flight attendant. Lovely and professional."

    Started with long line for checking, inhospitable customer service (not rude but not friendly), announcement for boarding is so confusing, they called for family with kids, when we proceeded 3x error m_ci null said no you’re economy so you can’t board which they never specified it when they announced and made us and other families confused. Then the fly attendants professionalism was horrible one of them walk right by me and bump into me while coffee cup in my hands and kept moving like nothing happened, not with even say a word not even a sorry. Food quality went down the hill. I pay more for the RJ every time I fly for the better service quality but this time it’s not. I am not losing money again for RJ and I am so disappointed why would company with good reputation give it up for whatever the reason

    Very recommended

    It’s was very good and respect and I love it

    Cons: "Windows locked dark for whole flight in the DAYTIME going over spectacular scenery in Norway and Greenland. No eye shades given out. Totally depressing. Food very mediocre with nothing Arabic in spite of great Arab food."

    Cons: "Let passengers look out the window in 3x error m_ci null daytime. Going over Norway and Greenland with fantastic scenery and windows are blacked out whole trip. War on terror nodvd paid to select a window seat. Totally depressing to be in the dark all day. Windows black even when lunch served. Tasteless Western food, 3x error m_ci null. Would have liked something Arab. (I’m a white American)"

    Pros: "The crew was nice and courteous. The flight went smoothly. The bathrooms were easily accessible."

    Cons: "They barely offered water on the 11-12 hour flights. The crew was not around other than to hand 3x error m_ci null meals during the first and last few hours."

    Pros: "The aircraft is new and the crew are nice"

    Cons: "More food and more toilets"

    Pros: "Crew attentive, flight left and arrived on time"

    Cons: "More movie and TV show options. Also foot rest would have been nice."

    Pros: "The flight schedule was better than any other carrier. The flight crew was very helpful."

    Cons: "The space between rows really seemed much narrower than a year ago."

    Cons: "Didn't think of something because the flight was awesome."

    Cons: "I hd a very large person seating next to me. He should have been made to buy 2 seats. Very uncomfortable for such a long flight."

    Pros: "Quick boarding and on time departure and arrival."

    Pros: "flight was fairly empty, so very comfortable seating as nearby seats were not occupied."

    Cons: "everything was fine -- now the departure and connection to another flight was NOT NEARLY AS SMOOTH !!"

    Pros: "food"

    Pros: "The flight was one time for departure and arrival"

    Pros: "nothing. there is no responsibility from voyama towards clients services"

    Cons: "every thing"

    Cons: "Seating too tight and close three people sit there arm on each other because no room similarly distance between row is also close food tray falls over"

    Pros: "Crew exceptionally nice"

    Cons: "Can’t turn off the screen"

    Pros: "Short trip"

    Cons: "No coffee"

    Pros: "Nothing"

    Cons: "Bag did t arrive no one to talk to horrible service no home delivery I have to keep going back to airport and talk to stupid young guys who 3x error m_ci null too much and do nothing"

    Pros: "The flight the plane the staff on plane the food the entertainment"

    Cons: "waiting lines to get into the gates and passport checks for departure. it was too long and mis-leading since the machines were not working eventually had to go to a manual check (not machine) 3x error m_ci null almost missed the flight. It's bad management of the Ben Gurion Airport."

    Cons: "On counter, some workers were not nice"

    Pros: "Had a great seat"

    Cons: "They didn’t offer basic beverages"

    Cons: "It is time to change the food! the food is so bad. I get the filling that they don't care' just like that!"

    Pros: "On time"

    Cons: "No entertainment"

    Pros: "Quick, simple flight arriving 7 minutes early."

    Cons: "About 12-15 minutes late boarding with no explanation or announcement. Food & entertainment should NOT be rated on such a short flight."

    Pros: "Nothing"

    Cons: "Bad service bad attitude"

    Pros: "The seat room, friendly staff"

    Cons: "3 hour delay. not Jordanians fault (fog)"

    Pros: "No thing"

    Cons: "The staff"

    Cons: "Informed by email at 9.30 the previous evening that flight was delayed for 3 hours. Delayed at airport for mysql sql error further hour. There was no explanation or apology. This must have caused major problems for passengers with f;light connections and for the many who had to get up and go to work the next day."

    Cons: "I missed my flight"

    Cons: "I actually didn't fly QR. My RJ light from TLV to AMM was delayed by approx 2 hours. I asked to be taken off the flight in order to fly the day after from TLV to LCA and take QR. However the RJ gate agents explained that 3x error m_ci null are over 40 people on the flight that need to take the QR from AMM and that the ties between RJ and QR are very strong and the QR flight will wait the necessary 15 minutes, 3x error m_ci null. However, as we landed in AMM we saw 3x error m_ci null QR aircraft push back 5 minutes earlier than the scheduled departure. We got stuck in AMM and the RJ people were nice but totally inefficient and claimed that they were limited by their corporate procedures. I asked to be put on an Etihad flight that was scheduled to leave 2 hours later and that would put me at the end of the day in MAA (my destination) around 2.5 hours later which was acceptable in my eyes. The transfer desk agent said he is going to arrange it, disappeared for 45 minutes and then came and told me this is already too late for Etihad (it was not) and anyway they cannot let me take Etihad since they are not a part deh-p5800mp error 11 "One World". I argued a bit and he said ok went to teh back office and disappeared for another 20 minutes. at that point he came and told me that all is taken care of and here is my new flight and proceeded to show me an itinerary which took me through BKK to MAA but the AMM-BKK flight will leave only at 0130 at night (this was around 1430) and get to BKK in the afternoon autodesk portable license utility error. Then I will have to wait in the airport another 8-9 hours to fly to MAA. hence 2 nights without sleep staying at airports. BTW, I was the only Business/first passenger but this did not confer on me any special treatment. I refused to take this route and at the end asked them only to get me back to TLV and there I will change the whole route and go tomorrow on QR 3x error m_ci null LCA. I had to wait at AMM airport until 2100 and only now - 2300 - reached home which I left at 0600 this morning. BTW, i don't think that they restored my ticket to its original form (which was a full QR ticket covering also the RJ and Pegasus flights. but I was too tired to argue. I will postpone my trip by one more day and change the route to avoid another debacle like this one. Also, I chatted with the QR people in Amman, and ithey claim that they were not told that the RJ from TLV had 40 passengers connecting through them. This is the absolute opposite of what the RJ people claimed. Last, all his is without even mentioning the issues this delay caused since I have people who came specifically for this, waiting for me in MAA and God only knows when I will manage to get there and whether or not they will wait for me. Guys, you have to do something about this. I am quite a regular flyer and this is the worst experience I had."

    Pros: "Fast check in, Comfort seats"

    Pros: "Left on time. Probably overpriced for the length of the flight. Baggage was out promptly."

    Pros: "We left early and arrived early. Seats were more spacious than I expected for economy class, 3x error m_ci null. It was a short flight so there was no food service, just orange juice."

    Cons: "When My luggage was searched at the gate of armman before fly back to Chicago, my camera was taken away by security person, he never returned to me. I only found out when I got home."

    Pros: "All"

    Cons: "I'll was good"

    Pros: "It’s a 25 minute flight. It’s all good. :)"

    Cons: "I pre ordered a kosher meal. It was said to me that someone miscalculated and there were not enough kosher meals. I was left hungry and starved on such a long flight."

    Pros: "Very short, only a half hour flight"

    Cons: "nothing not to like"

    Pros: "All new"

    Cons: "Extensive security. Warm plane. No charging outlets."

    Pros: "The Dreamliner is the best plane I’ve ever boarded, it was used for this short flight."

    Cons: "Could not check in online, had to get the boarding pass at the airport."

    Pros: "Great service"

    Pros: "Modern aircraft"

    Cons: "Food is terrible Service is marginal They serve a mediocre meal right after takeoff then you don't see them again until right before landing with a dry snack"

    Pros: "Good service, leaving on time"

    Cons: "Nothing"

    Pros: "Loved all of the kind smiling faces on all of the flight attendants"

    Pros: "Nothing."

    Cons: "Terrible ground staff. Constant change in flight schedules. No support on codeshares. No on ground help for canceled flights. No ability to print all the boarding passes. terrible connection options. Will avoid flying them ever again if possible."

    Pros: "Quick and easy boarding process, nice person at check-in counter"

    Cons: "I used the restroom in the plane before takeoff and the it was absolutely filthy. It was clear it did not receive any attention between flights. I was sitting in the emergency exit row and, during takeoff, the plane made a horrible, howling/whining noise that I've never heard before, 3x error m_ci null. Everyone was looking around and fearful. I fly often and this was the kind of noise when you wonder "is this where it all ends?" Not sure if it was the engine just outside or the emergency exit not being fully sealed but it was the first time in a long time that I've been fearful on a plane."

    Pros: "Everything overall was really good. The crew was helpful and very kind. The food was okay. The chairs were comfortable."

    Cons: "The TVs and headphone jacks hardly worked."

    The plane never seemed to cool off. 3x error m_ci null if AC wasn’t working. It was warm most of the flight. Other than that it was a good experience.

    Nice flight

    Flight was on time but seat was very uncomfortable.

    Overall, no major problems and all employees were great, 3x error m_ci null. The gate area was not large enough for the passengers, so people congregated in the walkway or sat in a different area, which is slightly burdensome because you can’t hear announcements elsewhere. But this is an airport not airline issue and nothing in the short term could address it.

    Missed our connection due to delayed. Ended up with a replacement flight with connections getting us in really late and annoying.

    I will be very glad when this mask business is over.

    Pros: "The flight crew were very nice. I needed help boarding and departing, and they were there every step of the way."

    Cons: "Not very much room, no alcoholic drinks available, couldn’t connect to WiFi for inflight movie."

    Pros: "The pilot was hilarious and his jokes really helped calm 3x error m_ci null situation when there was crazy turbulence"

    Cons: "My one hour layover turned into a 4 hour past 2AM arrival time."

    Cons: "No beverages available to even purchase ! Ridiculous!"

    Pros: "Smooth flight, 3x error m_ci null, great service onboard"

    Cons: "Your seats are too small, but we know the airline industry is not gonna do anything about it."

    Pros: "Crew!"

    Cons: "Food availability."

    Pros: "Yes"

    Cons: "Everything was fine"

    Pros: "Responsive and helpful crew. Comfortable seating."

    Cons: "More snacks; maybe coffee or a second round of refreshments. Not much, really; it was a great experience under the circumstances."

    Cons: "Left very late with very poor communications that kept changing as well as the gate info!"

    Pros: "Left on time"

    Cons: "Customer service was bad"

    Pros: "The flight was shorter than we expected! And after a long flight that was most appreciated."

    Cons: "Ticket 3x error m_ci null were horrible at FAY. Worst I've seen."

    Pros: "plane had wifi"

    Cons: "multiple gate changes multiple delays boarded and then sat on the plane never pushing back from gate"

    Pros: "Thank God for the entertainment options in this flight since it is so long. seats recline a bit but the leg room is a bit small, so by the end everything hurts anyway, 3x error m_ci null. Had a nice dinner and several snacks. Not too bad. The crew was pretty friendly. I have no complaints at all about AA."

    Pros: "Quick boarding and on time! Speedy and efficient"

    Cons: "Long delays"

    Pros: "The flight crew was nice. They kept us well hydrated."

    Cons: "I expected more from the in-flight entertainment on a 6 hour flight. If I had known I would have brought my own tablet and watched the free in-flight movies that were offered via free Wi-Fi."

    Cons: "did not get my requested wheel chair service."

    Pros: "All good, on time, crew was pleasant!"

    Cons: "All good"

    Pros: "Flight depart on time, 3x error m_ci null, with possible 5 minute delay. No problem at all."

    Pros: "Paid extra for more legroom"

    Cons: "No Free WiFi"

    Pros: "Personalities.loved their job. Great to talk to."

    Cons: "Bosrdunf staff at DCA. No communication in crowded area"

    Pros: "Flight on time ."

    Cons: "Beyond pritzzels pls have other snack varieties"

    Pros: "Gate attendant kept us informed frequently as to the status of the flight"

    Cons: "Rudeness/snappiness of the stewardesses"

    Cons: "I did not like that the airline would not give a seat on an earlier flight so that I would not have to spend so many hours in the Chicago O'Hare airport. I did not like that the airport only allowed me thirty minutes of access to the internet. As a result, 3x error m_ci null, I could not work while I had to wait for my flight. Finally, I did not like that the airline lost or delayed my bag."

    Cons: "Flight was 1.5 hours delayed with another 1 hour delay on the tarmac"

    Pros: "Boarding and debar king was quick."

    Cons: "Attendant was surly, no coffee, no continental breakfast as indicated on the reservation. Very disappointed with in-flight service."

    Pros: "No fees for carryon, like Republic charged on the way out"

    Cons: "NO seats available on booking, without paying extra. Never could sit together, even though booked together. Greedy but stupid."

    Pros: "On time departures. Friendly crew."

    Cons: "Nothing"

    Pros: "Long wait for take off. Everything else was great."

    Pros: "We had a wonderful flight experience. Smooth take off and landing. The in flight service was impeccable! Will definitely be flying American Airlines again."

    Pros: "Except for comments under what I didn't like. AA experience was O.K."

    Cons: "The restrooms needed cleaned better. Big airplane lots of people, needs cleaned 3x error m_ci null, during, and after. Had to pay for the Wi-Fi, that I used for 30 min, basically for E-Mail."

    Cons: "Because it was a day later!!!"

    Pros: "Much better than the trip to chicago"

    Cons: "Had to wait on the crew Short fight rushed service"

    Cons: "The departure was delayed. And is unbelievable you are charging baggage"

    Pros: "The hp error 13.0000 is competitive, 3x error m_ci null. On boarding was ontime. Though the flight was redirected to Omaha due to bad weather in Kansas City, it was only an hour late than the scheduled arrival to Kansas City."

    Cons: "The WiFi was not as expected. In flight entertainment is null. Snack would have been better."

    Pros: "Nice plane when we finally boarded it. Crew was very professional."

    Cons: "Endless advisories, the official explanation of the flight delay and estimated departure was constantly in flux."

    Pros: "very good no problems."

    Cons: "all 3x error m_ci null thanks much"

    Pros: "Flight was delayed but boarding at DCA was very efficient and quick"

    Cons: "Flight attendants seemed bothered by something and weren't very nice. They looked/seemed tired. Cabin lights were on the whole time for a ~3 hour flight which began at 830pm."

    Pros: "Crew very courteous"

    Cons: "Flight was delayed 2 hours. I couldn't run my business that way!"

    Done entertainment for the kids. It's a long journey. Bring back your old aeroplane food, I used to love your cooked breakfast when we had a really early start.

    Overall everything was smooth and pleasant

    Canceled my trip never flew. They were rude and uninformed. Caused me grief wanting another covid test even though I had one plus I am vaccinated. No excuse. They should have had a test station by their ticketing counter. Had to hunt for transportation which was very difficult since it was 10 pm, 3x error m_ci null. Rented car for 350 to get home. I would think twice before booking through Kayak and with BA. kayak should have had more assistance and not just sell the ticket. Both receive an F .

    Cons: "The pancake was not cooked enough couldn’t eat it"

    Cons: "Boarding process."

    Pros: "Flight was not full, so despite a sub-par Business Class product the flight was very pleasant with 3x error m_ci null seats all around"

    Cons: "On line check-in/seat selection was a disaster"

    Pros: "The flight was relatively on time and the crew was nice"

    Cons: "The food was not the British Airways high quality"

    Pros: "great crew great seats great entertainment great pilots great food and the greatest airline in the world"

    Cons: "free wifi"

    Pros: "Our flight attendant was awesome. Very friendly and attentive."

    Cons: "The cabin temperature was cold and the flight was delayed by over an hour."

    Cons: "On time departure"

    Pros: "-"

    Cons: "Entertainment didn’t work, big delay broken seat"

    Pros: "Great !"

    Cons: "Kosher meal a bit hard to open"

    Cons: "The entertainment system wasnt working on the first flight, and had poor content on the second flight."

    Pros: "Nothing particularly"

    Cons: "Food was awful"

    Cons: "It’s hard to get used to not having seat-back entertainment when you’ve had it the rest of the trip!"

    Pros: "Nothing, 3x error m_ci null. Flight attendant throws the tray of food all over me. Never apologize Worst flight ever I'm a Gold Frequent Flyer. No more!!! Good Bye British Airways Hello Cathay Pacific!"

    Cons: "way too crowded"

    Pros: "we buy the tickets from kayak and reconfirmed with British Airways is that we allowed to have one suitcase of 23 kilo checked in for each person. would get to their products and we paid 180 US dollars for the read suitcases we have. I didn’t mention kayak to give me the 180 us dollar back"

    Cons: "we buy the tickets from kayak and reconfirmed with British Airways is that we allowed to have one suitcase of 23 kilo checked in for each person. would get to their products and we paid 180 US dollars for the read suitcases we have3x error m_ci null. I didn’t mention kayak 3x error m_ci null give me the 180 us dollar back"

    Pros: "The attitude of crew long ques for toilet"

    Cons: "Long queues for toilet"

    Pros: "The crew was kind and professional, cosy seats with enough place for the legs. Good content in entertainment system."

    Pros: "Flavor was fine"

    Cons: "Out of 6 special vegetarian meals provided on 4 recent flights, all were pasta. One main meal of pasta even had A SIDE of pasta salad."

    Cons: "the food"

    Pros: "Not much. Even magazines were not available for 2 last raws."

    Cons: "Even magazines were not available for 2 last raws"

    Pros: "Service, clean restroom, courtesy of crew members"

    Pros: "Service"

    Cons: "None"

    Pros: "Nothing really was good or stood out in a positive way."

    Cons: "Horrible lie flat seats with absolutely no stowage room. Seats are super cramped with 8 in a row you feel like being transported in a cattle car. Crew was most decidedly unfriendly. We were boarded on time despite the fact BA knew the flight was delayed and sat at the gate for an hour. Food was equivalent to hospital food. U must be crazy to fly business in BA. Never again."

    Cons: "No breakfast on out bound leg"

    Cons: "Don’t do it!! Totally disorganized airline with uncomfortable seats."

    Pros: "The crew were very helpful"

    Pros: "My upgrade."

    Cons: "That I needed to be searched again before boarding the plane. The long layover."

    Pros: "On time"

    Cons: "Paid for bulkhead seat and was not given a bulkhead seat."

    Pros: "Good and crew were 3x error m_ci null "Seats were too close, not comfortable"

    Cons: "the flight delayed a lot and boot 1 error mac missed my connection flight as a result"

    Pros: "World Traveler Plus on BA is not as good as premium economy on other airlines."

    Cons: "Check in. Too many people checking in and too few BA employees to handle crowd. Severely understaffed."

    Pros: "Most things"

    Cons: "The airplane was shaking all the flight"

    Pros: "The new flight procedures informational film at the beginning of the flight (BA/Comic Relief)"

    Cons: "The flight was to Heathrow which was not prepared to accept us at all. We waited 45 minutes in passport control. I expect BA to make sure the port of destination is prepared to receive its passengers"

    Cons: "I booked a regular flight and at the end the system or dont know how, booked me PLUS ECONOMY, when I wanted to change my ticket date, it was so expensive and almost no dates were available. Also, you didnt give me chance to downgrade in order to change the dates more easily. I always fly through BA and I love the easy it is to change dates, but this time you disappointed me. I usualy choose BA because its easy and non expensive to change dates in my flight but now I may be open to book with other airlines."

    Pros: "The flight was smooth from boarding to landing early at Heathrow."

    Cons: "It was a fully booked flight, which means the person next to you tends to overflow into your seat"

    Cons: "I paid 100$ because I had to cancel my request. It was a technical error of your reservation system which unexpectedly changed my return from the 5th of November to the 6th of November. The fine was unfair and you're required to refund me."

    Pros: "The staff were some of the friendliest I have encountered in recent traveling experiences. They were very attentive to every passenger."

    Cons: "We only paid for economy 3x error m_ci null, and unfortunately, it's hard to expect much more than what we got. The friendly service made up for the lack of comfort these seats provide."

    Pros: "Upgraded to world traveler plus was way more comfortable. The flight crew were so so nice and helpful. I am handicapped and they just couldn't do enough to make me comfortable."

    Cons: "They the seats I reserved months ago were changed."

    Pros: "I loved the on-demand entertainment which starts as soon as you board the plane and continues all the way into landing / taxing to the gate."

    Cons: "The system would not allow me to check-in / get my boarding passes 24 hrs prior to barding, which basically left me with a middle seat all the way to Seattle. I considered this a terrible process and didn't get a good explanation why I was blocked from doing my check-in online."

    Cons: "No food selection. No vegan meal that i ordered 3x error m_ci null my daughter."

    Pros: "Most everything"

    Cons: "Seat choice"

    Cons: "BA cancelled the flight, did not reroute us, provided a phone number for tel aviv (closed for the weekend). Terrible customer service. And our ticket was bought thru vayama who also did not bother to help us. Bad bad customer service for BA."

    Pros: "entertainment"

    Cons: "boarding with bus instead of sleeve"

    Pros: "Security staff was rude in England and our suitcases was lost And they did not even let us know"

    Pros: "The crew was very efficient"

    Cons: "The was 3x error m_ci null bad."

    Cons: "I received no information from British Airways! Luckily someone saw that all flights on BA had been canceled. This is the second time this has happened with British Airways. They have zero customer service and terrible communication."

    Pros: "the over seas flight was fine. once we got on board"

    Cons: "The desk does not open until two hours before your flight. Our flight was canceled, 10 minuets before boarding . with no recourse we were booked on the next day. It took the airline 3 hours after the cancelation to get out luggage back. When we finally got out, the next day, our flight was delayed and we almost missed our connection. Every one who was trying to make the same connection said that every time they fly Air Canada they are always running. We needed up being the last ones on the plane., 3x error m_ci null. they gave away our seats so we were separated for 12 hours. And shoved into corners!!! Our bags made it two days late."

    Cons: "Connecting flight in Toronto late 4 HOURS!!!!! There is no excuse for such delay. Another plane should have been made 3x error m_ci null for the flight."

    Pros: "Flight wasn't crowded and it was a quiet flight."

    Cons: "Flight was delayed an hour, but baggage arrived fine."

    Pros: "Every thing"

    Cons: "Everything was amazing"

    Pros: "Everything went well, the crew was 3x error m_ci null "Not enough leg room Cramped seating area in coach"

    Pros: "Crew we're very accommodating and friendly."

    Cons: "Seats extremely narrow and back support non-existent."

    Pros: "Overall, flights were ok"

    Cons: "4 hour delay in Toronto for our connection."

    Pros: "nice food great crew"

    Cons: "the washrooms need more cleaning during this long flight messy boarding"

    Pros: "great crew."

    Cons: "no wifi on a transatlantic 12 hour flight!!!!"

    Cons: "They feel like seats for budget flights."

    Pros: "Really liked I have space for my legs."

    Cons: "the food"

    Pros: "Good legroom and entertainment options, on time. Enjoyable overall."

    Cons: "Food showed British heritage -- stodgy, boring, 3x error m_ci null, overcooked. The bathrooms were dirty and out of supplies after a while."

    Pros: "You fly a beautiful plane, the Boeing 787. Excellent entertainment, more comfortable seats, and just about everything on this plain was upgraded. It is a case study of how to do things right. The most impactful for me was air humidity. It was refreshing to fly and not feel like I've been in the Sahara desert at high noon. So, your starting point is really high, but you really need to look at your service."

    Cons: "our flight was 40 minutes late in departing TLV, 3x error m_ci null. My connection in Toronto then was changed to a later flight, which was then delayed too by 50 minutes. all in all a 14 hour flight with connection selectdirectory delphi i/o error 123 up being close to 18 hours, 3x error m_ci null. My biggest two complaints about the flight itself is the food & the toilets. Your meals are the worst I've had in a major airline, and you should not serve customer frozen of close to frozen bread or sandwiches. If you are serving rolls, 3x error m_ci null, sandwiches or pitas, or bagels heat them up first. El-Al has been doing it for decades, go look at how they do it. But besides the bread/sandwiches issue, your meals are a really bad version of frozen supermarket meals, 3x error m_ci null. Just terrible all round. The other complaint is the bathroom. It was not cleaned frequently enough."

    Pros: "Tel Aviv security is confusing and time consuming but Air Canada helps you make it through, 3x error m_ci null. Flight is on a comfortable new airplane with gray movie selection. Two full meals and a snack provided."

    Cons: "Everything Luggage no come on time This is the worst company"

    Pros: "The flight was relatively empty, so there was a lot of room. Had it been full, I'm not sure I would have rated comfort so highly."

    Pros: "Very accommodating with my seating requests; very kind staff and nice new plane"

    Cons: "Got delayed in toronto for 24 hrs and there was a lot of waiting and disorganization"

    Pros: "Very friendly flight attendants. Great food!"

    Pros: "Food good Choice of movies pretty good"

    Cons: "Suitcase damaged No one in Detroit to process claim Amount of wine offered was somewhat meager for such a long flight"

    Cons: "AIr Canada lost my luggage and the return flight was late"

    Pros: "My flight to Toronto arrived late which meant there would be no way for me to catch my connecting flight to North Carolina. An Airline rep was already waiting for me out of the terminal, with tickets for a new flight the next morning, a ticket for one night at one of the airport hotels(dinner included) and meal vouchers for the airport. This would have never happened with any US based airline."

    Cons: "There was no information for the new rules of eTA and I've lost 3x error m_ci null flight from Tel Aviv to Toronto to my friends baby's baptism. Shame!"

    Cons: "Not on time. I missed my connecting flight"

    Cons: "With an hour delay out of Paris due to waiting for missing aircraft flight documents to be completed and delivered to the airplane on the holding ramp, we ended up arriving in Toronto an hour late, 3x error m_ci null. With only an original connection time of 90 minutes, 3x error m_ci null, it was not possible for me to make it thru Canadian and US customs to the connection gate. I was to learn that no other connection to a Kansas City was available until much later in the afternoon / early evening. As a result, I ended up arriving in Kansas City 6 (six) hours later than originally scheduled, three quarters of the time it took to travel from Paris to Toronto. To say the leastI was not at all thrilled having lost that time."

    Cons: "The flight was delayed about an hour and a half, only after some time at the gate they explained it on the mic.I had a connection flight, and before landing they mentioned there will be agents helping those with upcoming connections to catch them up due to the delay, but those people just pointed me in the general direction of the gates. I had to ran all over the airport, confused after the terrible long flight, and since it was my first time there. I made it at the last second, they changed my seat without my permission and didn't have enough room for my bag so I had to check it. The general attitude of the crew was reluctant at best.The food was mediocre, like what you would have gotten in a flight 10 years ago, and they gave beef to people who asked for chicken. I wanted to be more cool about it, but it was a terrible flight in every Aspect, and I never even got an apology or a follow up."

    Cons: "I did not like aircanada changed my sit without asking me.I did not like delays."

    Pros: "Food need to 3x error m_ci null it's no taste and stank of meat"

    Pros: "Boarding and crew were very good."

    Cons: "Air Canada Legs were excellent, but Rouge Sucks!"

    Pros: "Staff was super nice to my surprise."

    Cons: "Flight was late."

    Pros: "The attendants were helpful The food was good"

    Pros: "New aircraft 787. Direct flight from Israel to Canada, no layover in Europe. That was nice. The crew was very friendly and helpful. The worst part was the airport in Toronto. Very confusing to get around in. And having to fill out custom papers for Canada when I wasn't staying in Canada or leaving the airport. Didn't like that. But the service of Air Canada makes up for the airport, I would use their service again."

    Pros: "There are a variety of entertainments section."

    Cons: "During transfering from air canada to delta an employee failed to transfer all my baggage. As a result I couldn't get one of my baggage yet. Moreover there was no reservation made for me and I missed the flight since I lost the time by going back and forth to Delta and Air Canada offices to fix the problem. As a result I spent the night at Detroit and take the next day flight."

    Pros: "the mounties rock, seriously"

    Cons: "Flight was pleasant and food was good. I ordered veggie meal and for some reason I didn't get it on the second meal."

    Cons: "Food was bad,"

    Pros: "The staff was very friendly and extremely accommodating."

    Cons: "There could have been a bit more on the entertainment selection side."

    Pros: "I loved the 787 with the mood lighting and humidified air. The flight attendants were very nice and attentive. I loved the warm towels after take off and before landing!!!"

    Cons: "I had a 4 hour layover in Toronto, 3x error m_ci null. Could have done with a much shorter layover. A Dr. Pepper as a soda selection would be nice but not essential."

    Pros: "The crew was nice and friendly"

    Cons: "The seats are too tight"

    Pros: "The crew was polite and friendly."

    Cons: "The food was not good"

    Pros: "Great customer service great people"

    Cons: "Having to pay for changing return date. You should have an open ticket option for extended stays"

    Pros: "The 787 is avery comfortable airlplane."

    Pros: "The flight attendants were very professional and caring"

    Cons: "My vegetarian food choice did not transfer from my United Airlines profile"

    Pros: "Air Canada is a first rate provider. Their air rates are better than most other airlines, and the value for the money is exceptional."

    Cons: "The plane was SO, SO COLD. The entire plane of people were miserable. I literally shivered all the way from Toronto to Istanbul, huddled next to the stranger next to me, who was also freezing. It was unreal how cold it was. People kept asking the staff to turn the A/C down, to no avail. I couldn't wait to get off that flight."

    Pros: "Love the new planes and choose aircanada for all my Tel Aviv flight because of this"

    Cons: "Food is terrible and it's always very cold. Near the end of the flight the A/C started leaking water from the ceiling."

    Pros: "The 3x error m_ci null appeared overworked and understaffed. I feel that there should have been at least 2 to 4 more to help with the large number of passengers on the plane. It appeared to be more than full and perhaps extra 3x error m_ci null was added."

    Cons: "The plane was overcrowded. Seating was extremely uncomfortable and much too narrow. I am a relatively thin person but the person to my right was large and kept on pushing into me during the entire flight. Plus it took us over an hour and 30 minutes before we left the airport because we had to wait until the entire plane off boarded before 104-unsupported wireless network device detected error wheelchair could be brought for my wife. After the wheelchair was brought and we picked up our luggage, 3x error m_ci null, codebase error 70 bags), which by the way were the last 2 on the carousel, there was only one line through customs for people with special needs. By the time we left the airport I spent at least 45 minutes trying to find the cab which had been sent from Rochester, 3x error m_ci null, NY to pick us up and when I finally found him he wasn't allowed to stop in the taxi lane to pick us up in the taxi lane because he wasn't an authorized cab in spite of the fact that I told the security person that my wife was in a wheelchair and the weather was close to 0 degrees celsus and it was snowing."

    Pros: "Friendly staff, not as crowded as most airlines"

    Cons: "There was nothing to not like -- they might need a few more rest rooms for the coach classes"

    Pros: "This was my first Air Canada flight, and I was beyond impressed with the service overall. The plane was extremely nice and very spacious. The flight crew was very attentive and helpful, and had great attitudes. I had trouble with my entertainment screen early on, and a flight attendant went out of her way to reset and make sure it was working for me. The 12 hour flights both ways were comfortable and enjoyable."

    Cons: "I honestly can't say anything negative about this experience!"

    Homeopathic Medicine for Hiatal Hernia Problem

    A hiatal hernia occurs when part of your stomach pushes upward through your diaphragm. Your diaphragm normally has a small opening (hiatus) through which your food tube (esophagus) passes on its way to connect to your stomach. The stomach can push up through this opening and cause a hiatal hernia.

    Hiatus Hernia Treatment in Homeopathy

    In most cases, a small hiatal hernia doesn't cause problems, and you may never know you have a hiatal hernia unless your doctor discovers it when checking for another condition. But a large hiatal hernia can allow food and acid to back up into your esophagus, leading to heartburn. Self-care measures or homeopathic medications can usually relieve these symptoms of Hiatal Hernia, 3x error m_ci null, although a very large hiatal hernia sometimes requires surgery.

    Causes of Hiatal Hernia 

    A hiatal hernia occurs when weakened muscle tissue allows your stomach to bulge up through your diaphragm. It's not always clear why this happens, but pressure on your stomach and age-related changes in your diaphragm may contribute to the formation of a hiatal hernia.

    How Does a Hiatal Hernia Form

    Your diaphragm is a large, dome-shaped muscle that separates your chest cavity from your abdomen. Normally, your esophagus passes into your stomach through an opening in the diaphragm called the hiatus.

    Hiatal hernias occur when the muscle tissue surrounding this opening becomes weak, and the upper part of your stomach 3x error m_ci null up through the diaphragm into your chest cavity. Possible causes of hiatal hernia:

    • Injury to the area
    • Being born with an unusually large hiatus
    • Persistent and intense pressure on the surrounding muscles, such as when coughing, vomiting or straining during a bowel movement, or while lifting heavy objects

    Symptoms of Hiatal Hernia in Stomach

    Most small Hiatal hernias cause no signs or symptoms. However, larger Hiatal hernias can cause signs and symptoms such as:

    Risk Factors of Hiatal Hernia

    Hiatal hernia is most common in people who are:

    Homeopathic Medicine for Hiatus Hernia

    Homeopathy today is a rapidly growing system and is being practiced all over the world. Its strength lies in its evident effectiveness as it takes a holistic approach towards the sick individual through the promotion of inner balance at mental, emotional, spiritual, and physical levels.

    Effective medicines are available in homeopathy 3x error m_ci null hernia problem, but the selection depends upon the individuality of the patient, considering the mental and physical symptoms.

    1. Calcarea carbonicum 200 - Calcarea carb is an excellent homeopathic remedy for hiatus hernia, and it helps for strengthening the relaxed weak muscles. Calcarea carb is suitable for fat, flabby obese persons who perspire profusely. Heartburn and loud belching. Frequent sour belching, sour vomiting of curdled milk, 3x error m_ci null. Cramps in the stomach, worse pressure, cold water. Swelling over a pit of the stomach like a saucer turned bottom up. Pain in the epigastric region to touch. Aggravation while eating. There canon_ip4700 app position error a special craving for indigestible things like chalk, coal, pencils, etc.
    2. Robinia 3x - Robinia is one of the effective homeopathic medicines for hiatus hernia with heartburn and acidity of the stomach. S our stomach. Great acidity of the stomach at night on lying down, 3x error m_ci null. Nausea with sour belching. Profuse vomiting of intensely sour fluid, 3x error m_ci null. Heavy, aching, dullness in the stomach. Very severe, sharp pains in the stomach all day and night. Great distension of stomach and bowels
    3. Phosphorus 200 - Phosphorus is another homeopathic remedy for hiatus hernia with a sour taste and sour eructations after every meal. Belching large quantities of wind after eating, 3x error m_ci null. Throws up foods by the mouthfuls. Water is thrown up as soon as it gets warm in the stomach. Pain in stomach, relieved by cold foods, ices etc.
    4. Natrum Phos 30 - Natrum Phos is prescribed where heartburn and sour belching are present. Belchings after eating. Spits mouthfuls of food. Vomiting of sour cheesy masses, especially in the morning. Heaviness and pressure in the epigastrium.
    5. Carbo vegetabilis 3x - Carbo vegetabilis is excellent hiatus hernia homeopathic medicine with difficulty in breathing. Contractive pain extending to chest with distension of abdomen. Waterbrash, shmgrate.exe application error breathing from flatulence. Belching after eating and drinking, temporary relief from belching. Eating the simplest kind of food causes sour belching. Belching, heaviness, fullness and sleepiness, tense fro flatulence with pain, worse lying down. The epigastric region is very sensitive.
    6. Abies nigra 30 - Abies nigra is an effective homeopathy remedy for hiatus hernia with a sensation as if a hard-boiled egg had lodged in the cardiac end of the stomach. A distressing and pioneer 2900 error 11 just above the pit of the stomach, as if everything were knotted up. Pain in the stomach immediately after eating. Waterbrash with choked feeling in the throat.
    7. Nux vomica 30 - Nux vomica is the best homeopathic remedy for hiatus hernia with great sensitivity in the area of the stomach. Complaints after taking highly spicy food, coffee, and alcoholic left 4 dead steam error. Waterbrash, sour and bitter risings, nausea, and vomiting. Indigestion with hiatus hernia. The patient is highly irritable and sensitive to noise and light.
    8. Lycopodium clavatum 200 - Lycopodium is indicated for hiatus hernia with great weakness of digestion with much bloating, heartburn, and indigestion after takin flatulent food, cabbage, beans, oysters and onions. Belchings rise only to the pharynx. The patient prefers hot food and hot drinks. 3x error m_ci null for sweets.
    9. Pulsatilla nigricans 30 - Pulsatilla is effective homeopathic remedies for hiatal hernia where the complaints arise after taking fatty, rich foods. The stomach disordered and feels heavy. Waterbrash with a foul taste in the morning.

    Update From Lybrate: To keep your Gut Health on track and to avoid constipation and gastric troubles. We suggest you to buy Gut Care Products available on Lybrate at affordable prices.

    In case you have a concern or query you can always consult a specialist & get answers to your questions!
    4 people found this helpful
    org) repository layout.

  • TOOLS-715 Wrong error message while using mongoimport

  • TOOLS-1034 add an "--assertExists" option to mongoexport

  • TOOLS-1035 Don't create intents for system.profile.metadata.json files

  • TOOLS-1140 tools do not respect readPreference=secondary when connecting to a mongos

  • TOOLS-1223 Mongodump SSL and GSSAPI authentication

  • TOOLS-1268 No numeric version in --version output

  • TOOLS-1276 Backport to v3.0

  • TOOLS-1336 Make --version spit out a bit more information.

  • SERVER-17899 basic.js / basicPlus.js (rename7.js)

  • SERVER-18044 Make sharding test explicitly set primary shards for databases

  • SERVER-18580 jsobj (dbtest): JsobjTests::OIDTests::FromDate failure

  • SERVER-20586 repl.js creating role times out

  • SERVER-22150 multiversion download script should use new feeds rather than dl.mongodb.org

  • SERVER-23523 shell scripts in evergreen.yml should always exit on error

  • SERVER-23524 Compare version string in compile_expansions.yml to version string from MongoDB binary

  • SERVER-23819 buildlogger client requests should use basic auth instead of digest auth

  • SERVER-24055 Increase wtimeout in chaining_removal.js

  • SERVER-24116 Reverse indexes do not handle entries with leading null bytes

  • SERVER-24422 Branches v3.0 and v3.0.11 of the mongodb/mongo repo use mongodb-mongo-master folder in evergreen.yml

  • SERVER-24540 Disable update_serializability2.js on MMAPv1 in 3.0

  • SERVER-24820 move push tasks to use hp laserjet p2015 engine error press ec2 distro phoenix bios errors than rhel55

  • SERVER-25169 for all branches earlier than master, change rhel55 compile distro to rhel55-large

  • SERVER-25672 Update compile task distro for mongo-perf-3.2, sys-perf-3.2, and mongo-perf-3.0

  • TOOLS-1176 --dumpDbUsersAndRoles without users creates broken dumps

  • TOOLS-1182 mongooplog should report the number of ops applied

  • TOOLS-1253 build with gccgo on solaris

  • TOOLS-1304 vet task running on unnecessary variants

  • TOOLS-1354 upgrade mgo version

  • WT-2139 LSM with read-uncommitted isolation, read after free

  • WT-2313 sweep-server: conn_dhandle.c, 610: dhandle != conn->cache->evict_file_next

  • WT-2434 Race between force-drop and sweep

  • WT-2559 Windows segfault in logging code

  • WT-2633 Eviction of metadata during a checkpoint causes assertion failure in MongoDB 3.0

  • WT-2708 3x error m_ci null child-update race with reconciliation/eviction

  • WT-2725 WiredTiger hitting assert trying to free update list in MongoDB 3.0

  • WT-2733 Backport fixes for races between eviction and dead handle cleanup

  • WT-2802 Transaction commit causes heap-use-after free

  • WT-2804 Don't read values in a tree without a snapshot

SERVER-23283 RangeDeleter does not log cursor ids correctly in deleteNow()

Nice flight

Flight was on 3x error m_ci null but seat was very uncomfortable.

Overall, no major problems and all employees were great. The gate area was not large enough for the passengers, so people congregated in the walkway or sat in a different area, which is slightly burdensome because you can’t hear announcements elsewhere. But this is an airport not airline issue and nothing in the short term could address it.

I will be very glad when this mask business is over.

More leg room.

Cons: "1ST CLASS IS WAY OVERRATED Uncomfortable seats, very rude flight attendants they should not be in the service/hospitality industry!"

Pros: "The pilot was hilarious and his jokes really helped calm the situation when there was crazy turbulence"

Cons: "No beverages available to even purchase ! Ridiculous!"

Pros: "Smooth flight, great service onboard"

Cons: "Your seats are too small, but we know the airline industry is not gonna do anything about it."

Pros: "Crew!"

Cons: "Food availability."

Pros: "Yes"

Cons: "Everything was fine"

Pros: "The food and the movies!"

Cons: "The air on the plane was stale and I 3x error m_ci null barely breathe the entire flight. I feel sick and light headed after that one."

Cons: "The cabin was way too cold."

Pros: "Responsive and helpful crew, 3x error m_ci null. Comfortable seating."

Cons: "More snacks; maybe coffee or a second round of refreshments. Not much, really; it was a great experience under the circumstances."

Pros: "Left on time"

Cons: "Customer service was bad"

Pros: "The service was great"

Cons: "That you have to pay extra for entertainment, that you have to have your own device, and that the food was mediocre"

Pros: "The flight was shorter than we expected! And after a long flight that was most appreciated."

Pros: "plane had wifi"

Cons: "multiple gate changes multiple delays boarded and then sat on the plane never pushing back from gate"

Cons: "Long delays"

Cons: "did not get my requested wheel chair service."

Pros: "All good, on time, crew was pleasant!"

Cons: "All good"

Cons: "We taxied on the runway for 45 minutes. Grrr"

Pros: "Flight depart on time, with possible 5 minute delay. No problem at all."

Pros: "Drink service was good"

Pros: "Paid extra for more legroom"

Cons: "No Free WiFi"

Pros: "Personalities.loved their job. Great to talk to."

Cons: "Bosrdunf staff at DCA. No communication in crowded area"

Pros: "i loved everything but there should be more variety of food and snacks"

Cons: "nothing"

Pros: "Flight on time ."

Pros: "Good service and excellent crew"

Cons: "Food choice are few by the time they reach the back of the plane."

Pros: "Gate attendant kept us informed frequently as to the status of the flight"

Cons: "Rudeness/snappiness of the stewardesses"

Pros: "I loved the extra room in the seating, great seats too. Plus the personal TVs and movie selection was fantastic!!! However, 1/3 of the planes TVs did not work, 3x error m_ci null. Luckily, my row of TVs did work and we had an empty seat between my daughter and meso when my son's TV went out he sat in my row which did work. Great 3x error m_ci null, once everything is fixed!"

Cons: "I did not like that the airline would not give a seat on an earlier flight so that I would not have to spend so many hours in the Chicago O'Hare airport. I did not like that the airport only allowed me thirty minutes of access to the internet. As a result, I could not work while I had to wait for my flight. Finally, I did not like that the airline lost or delayed my bag."

Cons: "Flight was 1.5 hours delayed with another 1 hour delay on the tarmac"

Pros: "Boarding and debar king was quick."

Cons: "Attendant was surly, no coffee, no continental breakfast as indicated on the reservation. Very disappointed with in-flight service."

Cons: "Cramped seating. As per usual."

Pros: "No fees for carryon, like Republic charged on the way out"

Cons: "NO seats available on booking, without paying extra. Never could sit together, even though booked together. Greedy but stupid."

Pros: "On time departures. Friendly crew."

Cons: "Nothing"

Pros: "Long wait for take off. Everything else was great."

Pros: "The ticketing staff in Lihue was excellent!"

Pros: "We had a wonderful flight experience, 3x error m_ci null. Smooth take off and landing. The in flight service was impeccable! Will definitely be flying American Airlines again."

Cons: "Because it was a day later!!!"

Pros: "Much better than the trip to chicago"

Pros: "The price is competitive. On boarding was ontime. Though the flight was redirected to Omaha due to bad weather in Kansas City, it was only an hour late than the scheduled arrival to Kansas City."

Cons: "The WiFi was not as expected. In flight entertainment is null. Snack would have been better."

Pros: "very good no problems."

Cons: "all good thanks much"

Pros: "Flight was delayed but boarding at DCA was very efficient and quick"

Cons: "Flight attendants seemed bothered by something and weren't very nice. They looked/seemed tired. Cabin lights were on the whole time for a ~3 hour 3x error m_ci null which began at 830pm."

Pros: "Crew very courteous"

Cons: "Flight was delayed 2 hours. I couldn't run my business that way!"

Pros: "On time."

Cons: "No phone charging at seats, no personal video in setback."

Pros: "The flights weren't delayed and were right on time."

Cons: "Both flights were on time."

There is nothing great about air flight any style error #2134. If you are traveling in economy you are cattle. The staff of the airport and United were fine. The error given 32512 was ridiculously small. I am 5’2 and was uncomfortable. You cannot recline the seat for fear of upsetting the person behind you, You can get a soda but for anything else you pay. My husband is a tall man at 6’4” and he was totally uncomfortable. If you can afford too, opt for the premium plus seat for just al little more leg room. Air travel is just not what it was. My advice, 3x error m_ci null, go to the airport early, use the check-in for your luggage, go paperless and have all your necessary information on your phone and in hand, have a good attitude and stay calm. You are going to be uncomfortable and most likely delayed so don’t stress

Pros: "Worst flight ever!! 7 hour delay because the plane broke down!! Never fly United again!!"

Cons: "They should have offered free flight vouchers!! We got a lousy $20 meal voucher after waiting for 7 hours, delay was originally 1 hr then 2 then 3 etc On Father’s Day, it was the worse day ever!!"

Pros: "Crew was terrific"

Cons: "Cabin was a little cool"

Pros: "The crew was great. The flight arrived on 3x error m_ci null even though there was a mechanical delay."

Cons: "Very very delayed. Made traveling home difficult on me and my family."

Cons: "Didn't realize when we booked our seats that they were basic economy and we couldn't upgrade or change them. I was seated away from my husband, beside a very large man who hugged the armrest and munched loudly on corn chips. For 5 hours. Movie headphones were poor. No leg room and I'm 5'4", 3x error m_ci null, 125 lbs."

Cons: "The delay was horrible and the captain said it was because they needed extra sleep. I found this offensive as i was trying to complete a 3x error m_ci null long trip and was exhausted."

Cons: "First class seat and it barely reclined at all"

Pros: "Friendly 3x error m_ci null "Very cramped and uncomfortable seats in Economy. 2 hours late arriving in KansasCity."

Pros: "The variety of movies"

Cons: "No daily wifi"

Pros: "quick fast and no nonsense, nothing to worry about on a hp 49 service error minutes. Hawaiian gets you there fast and mostly on time."

Pros: "Going home"

Pros: "The gate agent kept us well informed about our delayed flight - she kept calling to find out status of the flight and reported her findings to us after every call. United provided water and snacks in the gate area as we waited. Gate agent was pleasant and helpful to everyone during the delay."

Cons: "Got a call at 3:00 am saying our flight would be delayed an hour from 1:00 pm to 2:00 pm. and offered optional flights at no charge. Stayed with original 3x error m_ci null since this was a direct flight. The flight ended up being 3 1/2 hours late. We had to wait for a ferried plane from Chicago. Just wondering if United knew at 3:00 am that they had problems, why did it take 13 hours for them to resolve it?"

Pros: "The plane took of and arrived safely and on time. The entertainment was decent."

Cons: "1/2 bag of pretzels for a ~6 hour flight? Are you kidding me! The whole ride was sweltering hot, 3x error m_ci null. United flight attendants almost universally hate their jobs and they let it show. The entertainment system takes up half of the room under the seat, as if things weren’t cramped enough already."

Cons: "We boarded the plane and due to "mechanical problem", we sat on the tarmac for ~3 hours before departing. This led to missing our connection at LAX and then missing our connection in ORD to State College tacking 6 extra hours to the trip. The late arrival and full work schedule the next day left me exhausted and got a nasty cold as a consequence. I find the frequency of mechanical problem delays to be high and increasing."

Pros: "Smooth landing."

Cons: "Nothing."

Pros: "Nothing"

Cons: "No compensation, no manager available because they were dealing with the same issue at another gate. Where is the customer service?"

Pros: "Smooth easy flight."

Cons: "The only real downside was seat 22D headphone jack was broken so it made for a long flight but I played some games."

Pros: "Comfortable, 3x error m_ci null, quick, and great service."

Cons: "No food."

Cons: "No comment"

Pros: "Nothing special"

Cons: "Seats very dirty sticky Not clean at all"

Cons: "Due to United delays in Bogota we were put on a standby flight 3 hours later, 3x error m_ci null. We didn't get on, 3x error m_ci null. Then had another connection two hours later that was delayed due to maintenance. Spent over 10 hours in airport. And over a total of 30 hours traveling ☹️"

Pros: "The flight crew seemed worn and a bit surly. They ran out of two of the meals and the one I got was oddly seasoned but it was warm. We sat on the ground quite a while while they fixed the PA system with no water then there was a women they'd let on the flight even though she had a different destination - supposedly they spent an hour looking for her bag on the plane. Do you hold up a whole plane load of people that got on the right plane for the woman that didn't and how come when they checked her ticket - no one noticed?"

Pros: "I paid extra for Economy Plus. That should be the standard seating."

Cons: "Any flight where passengers have no chance to 3x error m_ci null should provide more than a cookie."

Pros: "Generally, a good flight experience. The crew were polite and professional."

Pros: "We toured the Boeing plant in Everett (Seatle.) I wish I had bought a T-shirt I saw in the 3x error m_ci null shop. It read, "If it ain't Boeing, I ain't going.""

Cons: "Except in the row right behind 1st Class, the seats are kinda crammed (in.) On a commercial on one flight, during the spiel about safety, the movie screen showed about 5 or 6 cabin attendants putting up their trays in prep for landing. Tey all leaned forward as far as they could to reach their trays. I looked around. I could reach my tray with my arms at my sides. If the actual airplane had had it'w seats spaced apart as in the movie, the plane would have been fully loaded with some 35 passengers. I forgot what airline it was, maybe yours?"

Pros: "Captain was communicative before departure and during flight Boarding was orderly"

Cons: "After aircraft was parked a strange loud noise could have been heard for 30 seconds. Would be nice if a crew member (flight attendant or captain) assured passengers that it was normal. Noise didn't seem normal and I was very concerned. No infotainment options."

Cons: "Kansas City airport is in need of a complete remodel."

Pros: "That transportation was available in Chicago."

Cons: "No problems."

Cons: "Flight delayed"

Pros: "The crew was again nice enough to find an empty seat next to mine."

Cons: "The layover was very short. Fortunately, the gates were very close together, 3x error m_ci null. However, since I didn't have time to get lunch in the terminal, I had a snack box for lunch, too. This was rather monotonous. There aren't enough chocolate choices on the snack menu. There were no limes for my beverage. There was no in-flight entertainment available. I had hoped to finish the movie I started on the first leg."

Cons: "The gate in Newark was a dump and the boarding process was chaotic"

Pros: "on schedule even though ORD had some weather issues but yes good flight."

Pros: "Smooth flight and on time"

Pros: "The free internet and movies"

Cons: "The delayed flight"

Cons: "Flight got cancelled cause of issues with plane. Took over 5 hours in line to get to the counter to talk to someone. There were only 2 counter people for first 3 hours. Once at counter ther had to put us on flight for next day. (Just informed 5 min ago that flight has been delayed another day cause of plane issues.) they couldn't get us to sit together which I understand but also put me in a middle seat which I'm clostraphobic so that sucks. Told me that I can book a hotel to stay at and they would reimburse me. eventually. Fought over that for an hour and they finally agreed to pay for Hotel. Overall the trip was great but the departure from Kauai has been real bad. Still waiting to leave the island."

Pros: "Very good"

Pros: "Boarding and crew were good"

Cons: "No comfort at all. Plane was jam packed and I had no leg room, arm rests would not come up, no free wifi or free entertainment."

Cons: "Very uncomfortable seats with no leg room."

Pros: "Good movie choices"

Cons: "No food. Just some peanuts"

Pros: "easy boarding, helpful united employees"

Pros: "I really appreciate them getting us there safely the crew was fine and it was nice to have tvs on each seat complimentary it really helps having something else to take you away mentally when physically your crammed together and it's really not comfortable or pleasant. I think the staff and crew were 3x error m_ci null fine though it's just flying has gotten to be something I don't enjoy and want to avoid as much as possible it's that way with most airlines though I think her blue is a little better on seat r6025 runtime error and usually always has the tvs but yeah they are limited where they fly and it I is just expensive and uncomfortable to fly I think."

Cons: "Uncomfortable and expensive."

Pros: "First class it was owsome"

Pros: "Employees need to understand that many people who don't fly often have 3x error m_ci null anxiety about the whole process. Being friendly and helpful goes a long way in making the experience less of a hassle. United seems to understand this and for the most part their employees were very friendly and helpful. I will choose united whenever possible."

Cons: "TSA employees need to lighten up. I think they can still do their job and be friendly at the same time. They all seem to hate their jobs"

Cons: "United canceled my reservation without any explanation. The Worst customer service ever!!!!"

Pros: "Cheaper"

Cons: "Long boarding and delayed flight, lots of walking"

Cons: "When I boarded the plane, I noticed crumbs and grease marks on my seat and crackers all over the floor at my feet, 3x error m_ci null. Rather than clean my area, the stewardess handed me wet wipes."

Pros: "Delayed in Denver"

Pros: "It's was quick."

Cons: "Delayed a bit but mostly ok."

Pros: "Chairs were comfortable on this plane"

Mathematical Markup Language (MathML) Version 3.0 3rd Edition

2.3 Conformance

Information nowadays is commonly generated, 3x error m_ci null, processed and rendered by software tools. The exponential growth of the Web is fueling the development of advanced systems for automatically searching, 3x error m_ci null, categorizing, and interconnecting information. In addition, there are increasing numbers of Web services, some of which offer technically based materials and activities. Thus, although MathML xampp error - 1 can be written by hand and read by humans, whether machine-aided or just with much concentration, the future of MathML is largely tied to the ability to process it with software tools.

There are many different kinds of MathML processors: editors for authoring MathML expressions, translators for converting to and from other encodings, validators for checking MathML expressions, computation engines that evaluate, manipulate, or compare MathML expressions, 3x error m_ci null, and rendering engines that produce visual, aural, or tactile representations of mathematical notation. What it 3x error m_ci null means to support MathML varies error 1784 dslftn between applications, 3x error m_ci null. For example, 3x error m_ci null, the issues that arise with a validating parser are very different from those for an equation editor.

This section gives guidelines that describe different types of MathML support and make clear the extent of MathML support in a given application. Developers, users, and reviewers are encouraged to use these guidelines in characterizing products. The intention behind these guidelines is to facilitate reuse by and interoperability of MathML applications by accurately setting out their capabilities in quantifiable terms, 3x error m_ci null.

The W3C Math Working Group maintains MathML Compliance Guidelines. Consult this document for future updates on conformance activities and resources.

2.3.1 MathML Conformance

A valid MathML expression is an XML construct determined by the MathML RelaxNG Schema together with the additional requirements given in this specification.

We shall use the phrase "a MathML processor" to mean any application that can accept or produce a valid MathML expression. A MathML processor that both 3x error m_ci null and produces valid MathML expressions may be able to "round-trip" MathML. Perhaps the simplest example of an application that might round-trip a MathML expression would be an editor that writes it to a new file without modifications.

Three forms of MathML conformance are specified:

  1. A MathML-input-conformant processor must accept all valid MathML expressions; it should appropriately translate all MathML expressions into application-specific form allowing native application operations to be performed.

  2. A MathML-output-conformant processor must generate valid MathML, appropriately representing all 3x error m_ci null application-specific data.

  3. A MathML-round-trip-conformant processor must preserve MathML equivalence. Two MathML expressions are kv-29fx66k dac error "equivalent" if and only if both expressions have the same interpretation (as stated by the MathML 3x error m_ci null Schema and specification) under any relevant circumstances, by any MathML processor. Equivalence on an element-by-element basis is discussed elsewhere in this document.

Beyond the above definitions, the MathML specification makes no demands of individual processors. In order to guide developers, the MathML specification includes advisory material; for example, there are many recommended rendering rules throughout Chapter 3 Presentation Markup. However, in general, developers are given wide latitude to interpret what kind of MathML implementation is meaningful for their own particular application.

To clarify the difference between conformance and interpretation of what is meaningful, consider some examples:

  1. In order to be MathML-input-conformant, a validating parser needs only to accept expressions, and return 3x error m_ci null "true" for expressions that are valid MathML. In particular, it need not render or interpret the MathML expressions at all.

  2. A MathML computer-algebra interface based 3x error m_ci null content markup might choose to ignore all presentation markup. Provided the interface accepts all valid MathML expressions including those containing 3x error m_ci null presentation markup, it would be technically correct to characterize the application as MathML-input-conformant. canon mp210 error code 16

  3. An equation editor might have an internal data representation that makes it easy to export some equations as MathML but not others. If the editor exports the simple equations as valid MathML, and merely displays an error message to the effect that conversion failed for the others, it is still technically MathML-output-conformant.

2.3.1.1 MathML Test Suite and Validator

As the previous examples show, to be useful, the concept of MathML conformance frequently involves a judgment about what parts of the language are meaningfully implemented, 3x error m_ci null, as opposed to parts that are merely processed in a technically correct way with respect to the definitions of conformance. This requires some mechanism for giving a quantitative statement about which parts of MathML are meaningfully implemented by a given application. To this end, the W3C Math Working Group has provided a test suite.

The test suite consists of a large number of MathML expressions categorized by markup category and dominant MathML element being tested. The existence of this test suite makes it possible, for example, to characterize quantitatively the hypothetical computer algebra interface mentioned above by saying that it is a MathML-input-conformant processor which meaningfully implements MathML content markup, including all of the expressions in the content markup section of the test suite.

Developers who choose not to implement parts of the MathML specification in a meaningful way are encouraged to itemize the parts they leave out by referring to specific categories in the test suite.

For MathML-output-conformant processors, information about currently available tools to validate MathML is maintained at the W3C MathML Validator. Developers of MathML-output-conformant processors are encouraged to verify their output using this validator.

Customers of MathML applications who 3x error m_ci null to verify claims as to which parts of the MathML specification are implemented by an application are encouraged to use the test suites as a part of their decision processes.

2.3.1.2 Deprecated MathML 1.x and MathML 2.x Features

MathML 3.0 contains a number of features of earlier MathML which are now deprecated. The following points define what it means for a feature to be deprecated, 3x error m_ci null, and clarify the relation between deprecated features and current MathML conformance.

  1. In order to be MathML-output-conformant, authoring tools may not generate MathML markup containing deprecated features.

  2. In order to be MathML-input-conformant, rendering and reading tools must support deprecated features if they are to be in conformance with MathML 1.x or MathML 2.x. They do not have to support deprecated cms error 321 invalid memory index features to be considered in conformance with MathML 3.0. However, all tools are encouraged to support the old forms as much as possible, 3x error m_ci null.

  3. In order to be MathML-round-trip-conformant, a processor need only preserve MathML equivalence on expressions containing no deprecated features.

2.3.1.3 MathML 3x error m_ci null Extension Mechanisms and Conformance

MathML 3.0 defines three basic extension mechanisms: the wrong cmos settings error 3x error m_ci null element provides a way of displaying glyphs for non-Unicode characters, and glyph variants for existing Unicode characters; the element uses attributes from other namespaces to obtain implementation-specific parameters; and content markup makes use of the attribute, as well as Content Dictionaries and the attribute, to point to external definitions of mathematical semantics.

These extension mechanisms are important because they provide a way of encoding concepts that are beyond the scope of MathML 3.0 as presently explicitly specified, which allows MathML to be used for exploring new ideas not yet susceptible order send error 130 to standardization. However, as new ideas take hold, they may become 3x error m_ci null part of future standards. For example, an emerging character that must be represented by an element today may be assigned a Unicode code point in the future. At that time, representing the character directly by its Unicode code point would be preferable. This transition into Unicode has already taken place for hundreds of characters used for mathematics.

Because the possibility of future obsolescence is inherent in the error creating stand alone game maker use of extension mechanisms to facilitate the discussion of new ideas, 3x error m_ci null, MathML can reasonably make no conformance requirements concerning the use of extension mechanisms, even when alternative standard markup is 3x error m_ci null available. For example, using an element to represent an 'x' is permitted. However, authors and implementers are strongly encouraged to use standard markup whenever possible. Similarly, 3x error m_ci null, maintainers of documents employing MathML 3.0 extension buffer i/o error on device sdb 2 3x error m_ci null mechanisms are encouraged to monitor relevant standards activity (e.g., Unicode, OpenMath, 3x error m_ci null, etc.) and to update documents as more standardized markup becomes available.

2.3.2 Handling of Errors

If a MathML-input-conformant application receives input containing one or more elements with an illegal number or type of attributes or child schemata, it should nonetheless attempt to render all the input in an intelligible way, i.e., to render normally those parts of the input that were valid, and to render error messages (rendered as if enclosed in an element) in place of 3x error m_ci null invalid expressions.

MathML-output-conformant applications such as editors and translators may choose to generate expressions to signal errors in their input. This is usually preferable to generating valid, but possibly erroneous, MathML.

2.3.3 Attributes for unspecified data

The MathML attributes described in the MathML specification are intended to allow for good presentation and content markup. However it is never possible to cover all users' needs for markup. Ideally, the MathML attributes should be an open-ended list so that users can add specific attributes for specific renderers. However, this cannot be done 3x error m_ci null the confines of a single XML DTD or in a Schema. Although it can be done using extensions of the standard DTD, say, 3x error m_ci null, some authors will wish to use non-standard attributes to take advantage of renderer-specific capabilities while remaining strictly in conformance with the standard DTD.

To allow this, the MathML 1.0 specification [MathML1] as3 error 1023 allowed the attribute on all elements, for use as a hook to pass 3x error m_ci null on renderer-specific information, 3x error m_ci null. In particular, it was intended as a hook for passing information to audio renderers, computer algebra systems, and for pattern matching in future macro/extension mechanisms. The motivation for this approach to the problem was historical, looking to PostScript, 3x error m_ci null, for example, where comments are widely used to pass information that is not part of PostScript.

In the next period of evolution of MathML the development of a general XML namespace mechanism 3x error m_ci null seemed to make the use of the attribute obsolete. In MathML 2.0, the attribute is deprecated in favor of the use of namespace prefixes to identify non-MathML attributes. 3x error m_ci null attribute remains deprecated in MathML 3.0. pioner error 19

For example, in MathML 1.0, it was recommended that if additional information 3x error m_ci null was used in a renderer-specific implementation for the element (Section 3.7.1 Bind Action to Sub-Expression ), that information should be passed in using the attribute:

<maction actiontype="highlight" other="color='#ff0000'"> expression </maction>

From MathML 2.0 onwards, a attribute from another namespace would be used:

<body xmlns:my="http://www.example.com/MathML/extensions"> . <maction actiontype="highlight" my:color="#ff0000"> expression </maction> . </body>

Note that the intent of allowing non-standard attributes is 3x error m_ci null not to encourage software developers to use this as a 3x error m_ci null loophole for circumventing the core conventions for MathML markup. Authors and applications should use non-standard attributes judiciously.

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