prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What is the research opportunity that is mentioned?

Read the following text and answer briefly.

Context 1: My Aspergers Child: COMMENTS & QUESTIONS [for Feb , 2017]
I emailed you a while back and you mentioned that I could email when I needed to  Thank you  I last wrote you in December that my son became involved in a dispute involving the local police  We have had 3 court dates  It keeps delaying due to not being able to come to an agreement  But the attorney, even though he was just vaguely familiar with Aspergers, has been very good with Craig  He has the compassion and excellence that is needed here  What started out very bad is turning into a good thing  It will probably take another 90 days or more 
But Craig is working hard  Too hard sometimes  He goes to therapy 3 times a week  Doing excellent  He's more focused and can calm down easier  He's got a lot on his plate but has support from his family  From his attorney  From therapy  And from his work 
He has been renting a room from a lady who has a son with ADHD  It is good for him  I'm a little worried though because since she smokes he wants to find his own place  With all the costs he has to balance it out financially  That is good  I can't help him more than I am which is good  He is stepping up and taking responsibility  He is listening much better 
He is going to have an evaluation today to get an accurate diagnosis  I understand that is a little difficult since he is an adult  Also the PTSD may cover it over  The attorney stated it would help to have the diagnosis 
Aware this is a long update, but thanks for reading  I am fighting much guilt still but I have a lot of peace now  My daughter and her 4 year old son also have Aspergers symptoms  So my life chapters may not close for a while  :-)
My name is Mac  I'm sure you're quite busy, so I'll get right to it I just wanted to pass on compliments on My Aspergers Child and your post, How to Implement the GFCF Diet: Tips for Parents of Autistic Children 
Me and my wife absolutely loved it!
I got a facebook message from him today begging to be able to come home saying he misses home and he will change  He says he will follow rules now  I stated to him the simple rules he has to follow which were - No weed in my house, or smoked in my house, coming home at curfew, going to school, no skipping, no drugs at school, and to drop the attitude of I am 17 I can do whatever I want 
I have made it very clear that if I see any drugs in my home I will be calling the police, as well as if I see signs of it being sold by him I will report him  (He has never had selling amounts in my house,     I believe it's being kept at his "friends" which of course I have no proof of    I just know it is not here 
I know my battle is not over by a long shot, I am sure we will have more consequences and possibly another being kicked out, but I am going to think positive and hope that he learned some form of a valuable lesson here 
Thank you so much for the guidance, never in a million years did I ever think I'd be on this side, (the one needing the help, as I am the one who helps )
I am going to go back to the start of the program like I said earlier and keep notes close by for reference 
Thanks for all you do, helping us all with ODD children/teens
I have a small company providing educational support services to a few families who have children with various disabilities in Ohio  One of the families has multiple adopted children of whom several have significant attachment disorders including RAD  As an experienced teacher and foster parent I have some experience in working with children who have extensive trauma backgrounds  However, I could use additional training  Also working with these children are two staff members with minimal background in attachment disorders who would also benefit from training primarily in behavior management  The primary caregiver to the children does a wonderful job managing their needs  In order to further develop team cohesion, I'm hoping to include her in any training as well 
Is it possible to schedule such a training session with you? If so, please let us know what will work for you including time, place, and cost  Thank you for your assistance 
I just listed to your tapes on dealing with an out of control, defiant teen  I'd like to ask your advice on a particular situation we have  Our 15 year old daughter is smoking pot almost every day at school  Because we had no way to control the situation, we told her, fine, go ahead and smoke weed  However, you will no longer receive the same support from us  You will not have your phone, lunch money to go off campus (she has an account at the school for the cafeteria she can use), and you will be grounded until you can pass a drug test  We will not be testing you except for when you tell us you are ready to be tested  She is now saying she's suicidal because she feels so isolated, yet she continues to smoke weed  In fact, she tried to sneak out last night but was foiled by our alarm system  For the particular drug test we have, I read it takes about 10 days of not smoking to pass the test  What would you do? Please advise 
I am having a problem with my 18 year old son, Danny, with high functioning autism  We finally had him diagnosed when he was 16 years old  I always knew something was going on with him but the doctors misdiagnosed him as bipolar  It's been 2 years now and he will not accept his diagnosis  He won't talk about it and when I try to bring it up he gets very angry  I've tried telling him that it's not a bad thing, that there's been many, many very successful people with Aspergers  He won't tell anyone and refuses to learn about managing life with it  He once shared with me that the other kids at school use it as an insult, like saying someone is so autistic when they do something they don't approve of  So he doesn't want anyone to know  He's turned down services that could help him  He has a girlfriend, going on 8 months  He won't tell her and they're having problems arguing a lot and I wonder if it would help for her to know 
I'm sad that he thinks it's a life sentence to something horrible instead of accepting, embracing it and learning about it more so he maybe can understand why he's struggling  I told him that he doesn't need to shout it out to the whole world but he won't even accept it himself 
I don't know how to help him with it and because he's almost 19 I have limited control now  It's made my life easier knowing what we're dealing with and I think his life would be easier is he accepted it 
Please help me help him 
I am a clinical psychologist in NYC who now has several (!!) children I see who have RAD  In 20 years of practice, I’d seen only one case  Now, I have at least three children with this  I have no training, per se, in working with this children though I know about setting structure, consistency, etc  I do a lot of work with parents about parenting  I work primarily within the school setting in a charter school whose mission is to educate children on the autism spectrum in a mainstream setting  We use Michelle Garcia Winner’s social thinking program with our ASD kids  I also work with gen ed kids in the school who are at-risk; the school is in the inner city from where the majority of our non-ASD kids live 
It would have been so much easier to mention to my adult son that I think (I know he does, but want to ease into the subject)
he has Asperger's when we were living together two years ago  He has since moved to Tennessee working in his field of interest
which is 3-D printing and software development  I am so happy for him that he has found his way into a job that he truly enjoys
even though he's socially isolated 
He's not diagnosed and does not know he has it  How I know is his classic symptoms being sensory issues (fabric feeling like sandpaper)
communication difficulties, meltdowns and much more  Throughout his childhood I just felt he was a bit different  Nothing major stood out and time
just passes, misdiagnosis of ADHD, low frustration, etc  We've talked about his ADHD numerous times (which I now know he doesn't have) 
It's so much easier to communicate with him now that I know he has Asperger's  I keep it "slow and low" in talking, with long moments
of silence and then we connect  It's really too bad that Asperger's got a diagnostic code back in the 90's, yet all the so called doctors,
physiologist's, etc, didn't know how to diagnose it  Too bad 
There seems to be no one answer to "should I tell my adult son he has Asperger's" from a few specialists I asked  He is typical Asperger,
complicated, highly intelligent (high IQ), anxiety at times, socially isolated, hard to make friends  Not knowing how he will react is the hard part 
How will he be better off knowing he has it? Do I wait to tell him in person, or ease into it with him over Skype? He likes direct, honest, concrete communication 
Why is this so hard for me? Maybe because no one know's if he is going to be better off knowing or not  Do you know if people are better off
knowing? I try to get up the courage to just let him know, then I back down 
I have been searching the web looking for advice and came upon your site  I am trying to read blogs, websites, books, and articles to help guide me  I was so happy when you said that I could ask you a question  My husband and I are struggling with my 27 year old son who lives with us 
Kyle is the youngest of 4 sons  He is a college graduate but never could find the "right" job  He has always been quiet and never had a lot of friends  Two years ago, his girlfriend broke up with him  Kyle had an online gambling addiction and was using pot all the time  After the breakup, Kyle was very depressed and started using heroin and finally told my husband he was using  He is now seeing a psychiatrist who has him on suboxone and antidepressants  He is also seeing a psychologist weekly for counseling but it does not seem to be helping 
Last October,, Kyle lost his job, got drunk, and was agitated and came home , fighting with us, damaging our home and being verbally abusive  My other son , age 32, who also lives with us called the police and Kyle got arrested  He is currently in the family court system  He went through an anger management course and now is in substance abuse classes  Kyle continues to verbally abusive to me and blame me for everything  He says he "hates me "and calls me terrible names  At times, he pushes my husband and intimidates me  My husband and I are so upset  We just hired an attorney for him because since he has been going to these classes, he is getting more depressed and not getting better  Kyle continues to drink while taking his meds prescribed by the psychiatrist and then he has his "moods " My husband and I have met once with the psychiatrist just to give him background information when Kyle started with him 
At this point, we do not know what to do  We never thought at this stage of our life, we would be supporting and spending our retirement money on adult children  I do not know why Kyle hates me, I could not have been a better mom  My husband and I have no life and just do not know what it the right path we should take  Kyle does not want anything to do with us  He spends all his time in his room playing football online We have tried tough love versus caring and love and understanding  Do you have any advice for me?
This whole ODD and ADHD is killing me as a parent  I work in the field of adult psych and addictions so I am well educated  I have been dealing with my teen being like this for almost 3 years and I totally lost my cool today with my 17-year-old son to the point I told him he is out of the house  He can never simple rules, comes and goes as he pleases sometimes doesn't come home, just recently back in school from several suspension for drug related    I am just so exhausted  He has made me hate life, hate being a parent and sometimes I just feel like not even being here  I bought your program in hopes to it would help, I am at week three and I feel things are getting worse    what am I doing wrong??
My partner hasn't been diagnosed yet but I know he has aspergers   day to day is a struggle   I feel I'm going crazy with how he makes me feel Feel let down constantly  He lies alot but I've been told they can't but I know he does I just feel trapped and unloved We have a 4yr old daughter together and my main worry with how he is that it will effect our daughter ; (his skills as a parent are so weak He can't disapline at all Feel so alone  he hides it well too I just wondered if things will get worse? He's angry so quick in arguments Scares me etc I can't leave as he's the main bread winner and our daughter loves him to bits Don't know why I'm writing this  Sorry if I'm going on and not making sense :(
I wanted to let you know about a research opportunity for children, teens, and young adults with autism  I am studying the effects of Brazilian Jiu Jitsu, and psychotherapy on helping people with autism develop subjective awareness of others 
I am writing you to see if this might help someone in your practice, or to see if you might know of someone with autism who may benefit from participating in this study  The requirements of the study will be:
1  A participant should be between 7-21 years of age and have a diagnosis of Autism Spectrum Disorder 
2  The participant should enroll in an approved Jiu Jitsu Academy and attend at least two sessions a week for a period of six months 
3  The participant should enroll in social skills groups, provided by my office or be in a steady psychotherapeutic relationship in your office, at least once a week, or minimally two to three times a month 
4  The participant will be given a SRS (Social Responsiveness Scale) test at the beginning of the study, at three months, and again at six months 
If you know of anyone who might benefit from this novel approach to helping to develop social awareness in autism, please do not hesitate to contact me for further information 
I have a 10 year old daughter who has outbursts with prolonged crying almost like tantrums that 2 year olds have when they cannot express themselves 
I had her in therapy from age 6-8 years old for the same thing but I feel that the sessions didn't really help much 
She has severe sensitivities to light, sound, vibration, frequencies which trigger irritability and crying 
We changed her diet and tried getting her involved with activities but she is anti-social and prefers reading than being social  She is terrified of change even in daily routine (even that will trigger prolonged crying) 
It frustrates me because I don't know what else to do with her behavior 
I've tried acupuncture (she refused at the first session); she refuses massage too 
She is an honor-roll student at school and has very minimal issues at school but if she has had a bad day it does result in a tantrum or crying and defiance 
How can I get her tested for Asperger's Syndrome?
Last night our 24 year old son with Aspergers told his dad and I that he is pulling out of the 4 college classes that he recetnly enrolled in because he has not been attending class or turning in his assignments  He paid $2800 (his own money) for tuition and I reminded him of this when he told us but it did not seem to bother him 
This is the 3rd time he has started college courses and has not completed them  (He also took some concurrent college classes while he was in high school that he failed)  This is a son who basically had a 4 0 grade point average through 10th grade and got a 34 on the ACT the first time he took it 
With the news that he was once again not sticking with college courses I did not sleep well  When I got up this mornning I began looking online for help in how to deal with his situation  I found your "Launching Adult Children With Aspergers" and purchased it  Most of what is included are things we have done or did with our son throughout his life  I was hoping for more help so I am emailing you now in hopes of more specific ideas 
We noticed some things with our son, Taylor, as a yound child but as we had not heard of Aspergers at that time we just did what we thought would help him  As a toddler and a child at pre-school he generally went off on his own to play  When I talked to his pre-school teacher about my concerns (that I was worried he would end up a hermit) she said she did not see him being a loner and that he seemed to interact fine with others in many situations  We worked with him on making eye contact when talking with others  We explained different emotions in people's faces and mannerisms to help him know how to interact with others  We discussed the fact that people would say things that did not mean what they souneded like - such as "I'm so hungry I could eat a horse"  As we did these things he worked hard to better understand communication with others 
During his 4th grade year I had a teacher from the gifted program ask me if I had ever heard of Aspergers  I told her that I had not heard of it  She proceeded to read me some of the charateristics and so many of them described my son  So we had him tested by the school district during the summer between 4th and 5th grade and they did find that he had Aspergers but that he was high functioning  We then set him up with and EIP which stayed with him until his sophomore year  We pulled him from it at that time because we had moved and the new district was requiring him to take one class a day that was a study class  This reduced the number of required classes he could take and he was doing fine with his studies at the time 
It was during the 2nd half of his Junior year that we noticed some of his grades going down  Then during his Senior year is when he started skipping classes and not doing assignments  We had not realized it before then but we soon became aware that he was addicted to gaming  He would go to the library or somewhere else on campus and play games on the computer rather than go to class  It was also at this time that he began lying about his actions (so as not to get in trouble) 
Based on his grades and his ACT score he received offers from colleges for full tuition scholarships  He chose the college where he had taken concurrent classes during his high school years  But he proceeded to skip class and not turn in assignments so he lost his scholarship and quit attending college  During this time he was only able to find employment through an employment agency where he was mostly sent to manuel labor type jobs (which is not something he enjoys but he did it anyway)  It was during this time that at one place had gone to on numerous occasions he was told if he came late one more time they would tell the emplyment agency they did not want him to come there anymore  (This seemed to make an impression on him because he has continued to be reliable and responsbile at his places of employment) 
At 19 1/2 he left to serve a 2 year full-time mission for our church  He completed his mission successfully  (I don't think it was without some struggle, stress and depression, but he was able to pick himself up and move on from those times) 
When he came home he started working for the employment agency again but began looking for employment elsewhere  He got a job at a local Chick Fil-A where he has worked for 3 years  He started college again shortly after he came home but as before it was short lived  He did finish out the semester but failed most of the classes due to his skipping class and not turning in assignments  When he skipped class he would usually sleep in his car 
Taylor's life consists of working (where to the best of our knowledge) he does well, he is reliable and his employer likes him  When he comes home from work he either sleeps or plays video games or other games - such as kakuro  He spendes most of his time in the basement where his bedroom is and this is where he games  Taylor owns his own car, bought his own laptop and very rarely spends money  He pays us $200 /month to still live at home, unloads the dishwasher on a regular basis and does the weekly garbage  However, his room is a mess and he only cleans his bathroom when I tell him he needs to clean it 
Taylor used to read quite a bit and loved to learn  It has just been in his adult years that he has not read as much - I think because of his gaming addiction  Taylor goes to church on a regular basis but sleeps through the main meeting  In Sunday class room settings he stays awake - I think because he is able to particpate in discussions 
Taylor has only had 2 real friends since entering Junior High school  And as of now he only keeps in contact with one of them who still lives in Georgia  We have lived in Utah since the summer of 2007 and he has never had a friend to do things with since we have lived here  He has two younger siblings, a brother 22 and a sister 20  They love Taylor and spend time with him when they are home  They are both at college and doing well 
Throughout Taylor's school years he has seen a counsleor on a fairly regular basis  One summer during junior high he attended a weekly class where he interacted with other kids with Aspergers  We did see a lot of change in him from this group  After he returned from his mission he went to see a counselor for a short period - this counselor tried to help him with some social skills  His dad and I went with him the first 3 or 4 times but we found out that after we quit going with him he only went a few more times and then scheduled appointments but did not show a couple of the times  We only found this out when a bill came for a "no show" appointment 
I don't know if this is too much information but were are in dire need of help for him  In the information that we purchased from you you mentioned that you do coaching for Aspergers adults  I don't know if you can help us but I thought I would check with you just in case 
Alas I think I have found your information too late to save my marriage but I am hoping to save myself 
I am currently going through a very very painful separation after a 27 year relationship with my husband whom I am convinced has aspergers syndrome  It is a long and painful story and I am desperately trying to process it all alongside dealing with a very conflictual separation  My partner is angry non communicative and totally dismissive of me and our long shared history 
He walked out last year after I discovered he had been visiting massage parlours and developed a relationship with an illegal Chinese escourt whom he subsequently moved in with  He had been seeing this woman behind my back for over 18 months  The pain of all this indescribable and his dismissal of my pain and very existence beyond belief 
Leading up to this I had been battling anxiety and depression which my husband found very hard to cope with 
Over the years of our relationship I knew something was off but I just could not put my finger on it  I often felt a complete lack of validation and empathy  Communication was also difficult as my husband was defensive and unwilling to look at issues in our marriage 
Please Mark could you help me validate some of this pain and try and make dense of 27 years of my life without drowning in fear guilt and despair about my future 
Thank you for listening and your site 
I have had problems with drunkenness, being late for school, not handing in school work, buying pot from a dealer etc  I chose to focus on the drinking and did the grounding then (grounding happened 3 times)  I also stopped sleep overs at friends 100%  I have stopped handing out money for no reason or even buying treats like chocolate 
I did lose it one evening (and didn't do the poker face) when I was trying to unplug the internet at midnight on a school night (she’s always late for school so I am trying to get her to sleep at a reasonable hour)  I was physically stopped and pushed around so I slapped my daughter (it was not hard)  This ended up with her saying she didn’t want to come home (the next day after school)  By this stage, I also had enough and didn’t go get her  I thought I am not begging  You will run out of money soon  It was quite a relief to have some peace  Daughter’s Dad was in town (from another country) and called a family meeting with the counsellor  To cut a long story short, daughter and her counsellor put it on the table that daughter wants to go live somewhere else (with her friends family) because of the stress at home with me (we live on our own) (i e  stricter rules and her bucking up against it) 
I didn’t really want this but made a compromise that daughter would go there Tues morning – Friday afternoon as the friend is an A student whereas my daughter is failing  They do the same subjects  I made the decision at the end of the day based on what is good for me – some time away from the daughter  I also thought of your book when the child went to live with the grandparents – daughter will dig her own hole over at the friend’s house  They have a week day no going out policy which made me think it is OK  I went and discussed with them the problems experienced (drinking, pot, late nights, not handing in work)
I am also trying to follow the let go of school thing per your book  I find it really difficult to remain calm when I can see daughter on her phone and watching series (when I have her on the weekends) when I know there are projects due  I hired her a private tutor once a week for help with a subject  The tutor has just fired my daughter for not handing in work and being not committed  It’s not the first time private tutoring has not been appreciated  The school give me a report back on a Friday as to whether everything is handed in  The deal is – if the work is not handed in – no pocket money and no Friday night out)  Her school is a "progressive" school and there are no repercussions for her being late or not handing in work  I would change schools if I could but there are only 8 months left of school (she turns 18 in August) 
We have just completed the first week and beginning week two of your material  We are agreeing with your take and see our son and ourselves in most of what you are saying  Prior to finding your material and starting your program we had been having extreme out of control behaviors and had to call the police because he was breaking things in our house and pushed my husband  This happened three weeks ago  After that incident we took away privileges ie  PS4, phone (which had already been taken for a few days), and friends  So, last week while doing your program he already didn’t have privileges and has continued with poor behavior – name calling, throwing things, slamming doors  We are not sure when to give privileges back  He has been given the privilege of playing with friends on occasion  His 13th birthday is tomorrow  This past weekend, for his birthday my husband and he went boar hunting  Of course we debated about it but decided to go ahead since it was his bday  We are cooking some of the meet on the grill tomorrow night for his bday and inviting a couple of his friends over for a cookout  No more gifts other than cards and balloons  We are wondering if we should go ahead and give him his privileges back and not sure how to do it  Last Friday morning we attempted to talk giving him a date to return privileges and that conversation ended with him getting angry but he gathered from our conversation that he is getting his stuff back on his bday  We are starting week 2 assignments today but not sure how to handle what was already in place  Of course, we aren’t seeing the respect and responsibility we are looking for but realize it has been a long time  We were wanting him to pay for his phone and thought it might be a good time to introduce that idea  Allowing him to earn his phone  We expect that he will be angry with this idea and not sure how to implement 
My son and myself are interested in a inpatient Aspergers program  We line in Calif which is preferable  My son is very high functioning and was diagnosed dry late  He was eight years old  He has never been in or attended a full day of class  Partially due to depression,anxiety, and trouble with his ADHD also his aversion and being bullied and of course his Aspergers  He will not attend his freshmen year due to surgery on both Achilles' tendons from walking on his toes  With physical therapy he should be ready by his sophomore year! We all feel he needs in patient therapy to give him the tools on how to work with his issues in a structured setting and a place that will give him tools for the rest of his life 
In my utter desperation to find a way to get some help for my daughter's increasingly challenging behaviour I trawled the internet to see if I could find some strategies that would provide specific methods on dealing with teenagers with Asperger's syndrome  When I came across your website, I couldn't believe that every statement you made was exactly what I have been going through with my daughter  She has just turned 14 last week, and was diagnosed with Asperger's/ Autism Spectrum Disorder 15 months ago  I have already been seeing a child psychologist for the past five months, however the methods she has been advising have not been very effective 
Our main difficulty with our daughter is her overwhelming obsession to use her cell phone (and to a lesser extent her laptop) constantly  Without any restriction, she will be on it every minute of the day, and will be awake until the early hours every day  We have tried to incorporate her input around rules as to when she has to give in her phone, but she is unwilling to compromise on a time that she should give it to us, believing that she should have unlimited use  I believe she is unable to do any adequate study or homework, as she is constantly having to look at the phone  We have tried to put rules in place that she has to give in her phone and laptop on school nights at 22:15  If she is able to do this then she is given rewards, and if she doesn't then she knows that there will be consequences  The consequence has been restricted use the following day  However, this is usually where we fail, because taking her phone away from her results in tantrums, screaming, and even threatening to harm herself  This behaviour is relentless to the point where the whole family becomes deeply distressed, and inevitably results in her getting the phone back 
This obsession is affecting her schoolwork, and more severely her eyesight  She has become very shortsighted, and her eyesight continues to deteriorate as a result of holding the phone or laptop very close, and mostly in the dark without any lights on  My husband and I have a constant battle on our hands daily, in all areas of discipline with our daughter, but our main concern is that we have been unable to find a way to minimise this obsessive behaviour centred around her phone and laptop  Please can you provide some strategies that can help us specifically with this problem 
First of all, I thank you for developing this program and I am only at the first stage of assignment 1  I have loads of books I have bought, attended psychiatrists for my son and myself, family therapy, occupational therapy, begged and prayed for change but have been dealing with behavioural issues for so long I am definitely exhausted and resentful 
I am a mum to a 15 yr old boy with ASD, dyslexia, OCD and ODD  Sorry to focus on the labels but just to give you an idea of what I am dealing with  I also have a 13 yr old son whom finds his brother’s behaviours difficult, embarassing and challenging  My husband whom is not in great health ( he had a cerebral aneurysm clamped two years ago and has two further aneurysms that are inoperable so endures fatigue, headaches and stress)  We have however a pet cat that is very social and a calming influence in the home! I was fortunate enough to have loving parents but I lost both my mum and dad in 2008 and 2015  My inlaws are elderly and quite directly say they are too old to help us so it feels we are alone in dealing with the issues we have 
I am desperate for change as the household is one of stress and anger and I feel all the control lies in my son Patrick’s hands  I am hopeful your programme can make life better for all of us but I wonder if it is too early to ask you two questions?
The first lies with what to do when Patrick goes into my other son Brendan’s room and will either turn on a light when he is sleeping, yell when he is on his phone or create some disturbance  He will not leave the room when asked to do so and the situation always escalates into yelling and Brendan attempting to physically remove him  This happens regularly and always ends badly with doors slamming, my husband being woken and myself in tears feeling the lack of control and also I admit I seem to think “Why me?” which rationally I know is of no help 
The second problem is leaving the house for school  Patrick refuses personal hygiene (either morning or night) and any request to even brush his teeth is fraught with swearing and abuse  If I can get him to shower, he will watch the water roll down the drain and turn up the water really high temp (mu husband has had to turn down the thermostat on the hot water service) without so much as getting wet  My husband leaves for work at 6am but I leave at 745 to work as a nurse in a busy outpatients department in the Alfred Hospital (Melbourne)  My work is my sanity as it is a paid break from home but most days I am late which is causing considerable stress and anxiety not to mention my responsibility to do my job  Patrick simply refuses to leave the house and as much as I am tempted to just walk out and leave I know the house would be left unlocked and wonder if Patrick would even attend school  The time I need to leave is not negotiable but Patrick uses this to his advantage and seems to delight in stressing me out and subsequently speeding to work in a frazzled mess 
The interesting and frustrating element in all of this is that although he is socially isolated at school (he has no friends) and academically challenged his behaviour at school is not a problem  He is quiet and his teachers report he does his best and is compliant and well mannered  It is like a Jekyll and Hyde situation where another side of him at home is so angry and abusive yet at school this behaviour does not happen 
I’m Jackie, I now work primarily as a freelance tech writer, after starting my career in software development and moving on to teach IT to young adults at a variety of colleges and schools 
My freelance work is pretty varied and looks at many aspects of the computer industry as a whole, and I’ve just recently completed a piece which gives help and advice to anyone wanting to become a game designer, which you can read here: http://www gamedesigning org/become-a-game-designer/  It highlights the hard work and effort it takes to get into such a role, and also how you can further your career and continue to learn and improve as you go  I hope you’ll agree it shows that starting work in the industry takes dedication and skill and that becoming a game designer isn’t just a fly-by-night job!
If you’d be interested in sharing a quick mention of my work on your blog that would be really wonderful and I’d appreciate the chance to get my work out there to a wider audience  Alternatively, I’d be happy to write a short blurb or paragraph or two (or a longer piece - just let me know) highlighting the key points because I think some of your readers might get a lot of value from it 
My son just turned 15 and is a freshman in high school  Although this is his first year in a general ed environment, he is struggling with behaviors in school  He has meltdowns and does not express why he would have them until much later  Once we all know what caused it, the school will accommodate him and try to "change up" things so as not to cause his meltdown  Once that is resolved, another issue comes up and causes him to melt down  He is a high functioning and academically does well, when he wants to do the work  We battle at home over homework  He does not care how it is done, as long as he hands it in  He thinks failing a test is ok, at least he took the test  Homework is never on his mind when he gets home from school  If I never prompt him, he would never open is backpack  He can be aggressive but is never intentionally trying to hurt anyone  He may push over a chair in school, but it is not directed at anyone  We know how that in itself could hurt someone who gets hit by it though  He is defiant in that he only wants to do what interests him  He does not go out by himself (still immature), or abuse alcohol or drugs and never curses  He is a very funny kid and very talented  His main problems are task avoidance and seeking attention  He can be disrespectful to adults in that he is "cheeky" with them, trying to be funny or cute  And he has no "filters" 
I’ve just finished reading your Living with an Aspergers Partner ebook  I found it so informative, thank you 
You offered some personal advise, and i wanted to run a situation past you and seek your input as to a strategy for what to do next 
I’ve been seeing a guy for about 7 months now who I believe has Aspergers  I came to this conclusion months ago and I don’t think he realizes, (or acknowledges) although he is aware he has some traits 
He’s highly intelligent and successful, a pattern seeker, has a tendency to focus on the project to hand to the total exclusion of all else for as long sit takes (work or home) socially awkward (has learned coping strategies), sensitive to loud noise, high anxiety with control strategies, black and white thinking etc  He’s currently not working and I’ve seen a slow withdrawal over the last 6 weeks, including the need to ‘escape’ and leave a situation at least once 
He also has a bipolar ex overseas who has primary custody one daughter where there has been ongoing patterns of drama which has recently increased 
Over the past couple of months (since stopping work and drama increase) I’ve gone from being ‘wonderful’ in his eyes to him now being sorry and not having the ‘urge’ to spend close/intimate time with me and offering friendship  Since he shared that with me in a message he’s stonewalled and has retreated to the safety of minimal messages and talks about not knowing what best to say and not being able to find the right words somehow 
He’s a good kind man who I feel is struggling  I’m concerned about his anxiety and possibly the risk of depression  I’m fairly resilient and whilst i’m disappointed he doesn’t want to pursue a relationship with me, i’m concerned for him and his well being  One of his very few close friends is also just leaving the country to live overseas 
The strategy I’ve used so far is simply to back off and give him space  I’ve asked to take him up on an original offer he made to talk but haven’t pushed it  I also haven’t been aggressive or accusatory in the few messages i’ve sent 
Any advise you could give would be greatly appreciated,
Carli who is 10 years old and has had behavioral issues her whole life  The other night she came home very upset after having a conflict with a friend  She was at her friend's house and her and her friend wanted to get on the computer and the older sister was using it  Carli made up a story that someone was at the door to get the older sister off the computer  Her friend didn't understand that she was making up a story to get the sister off the computer  She got excited that someone was at the door and ran downstairs to answer the door  In the process of getting the door, she fell and yelled at Carli  Carli became extremely upset  She was able to control her feelings at her friend's house, but when she came home, she proceeded to cry extremely loudly for over an hour  Her dad spent most of that time with her, talking to her and trying to calm her down  After an hour, I asked him if he could please tell her to be more quiet because the other members of the household were trying to go to sleep 
My question is    how do I as the girlfriend, handle this? He did not like that I asked her to be quiet  We have a rule that if she is having bad behavior, and can't calm down in 5 minutes, he takes her out of the house because her yelling doesn't stop for a long time and is very upsetting to everyone in the household  I would like to ask him to do this with this kind of situation as well  Is this a reasonable request? His thought was that she shouldn't be made to calm down, because everyone handles being upset in a different way  But, she was literally sobbing and wailing very loudly 
My other question is should she have been told that if she wouldn't have lied, this wouldn't have happened? She has a history of lying and of not accepting responsibility for her actions  My boyfriend became very upset with me when I brought this up  He was being very sympathetic and understanding to her  I feel like he was giving her negative attention, and being an over indulgent parent by not putting his foot gown and saying, "you can't carry on like this, even though you are upset"  Please let me know how we can handle these situations better 
I am contacting you for help with adult AS  I am taking initiative to pre screen potential therapists to help my current boyfriend get therapy and help with Adult AS 
He has seen many therapists, but it seems like they aren’t really helping him with his problems  They don’t seem to understand how his (undiagnosed) AS would affect therapy approaches  For example, he may not share enough in therapy session and I’m assuming an AS therapist would recognize that is part of the AS and employ strategies to get information from him that helps with treatment  Sometime he tunes out when he is processing something heavy or that he doesn’t want to hear necessarily, or he gets distracted and I’m hoping an As therapist would recognize that and get that he may need repeated something for example, if this is happening 
He is currently suffering from depression that appears clinical in nature as well as reoccurring negative thoughts about something specific that has been worrying him about our relationship  Today he told me these reoccurring thoughts happen during all waking hours unless he watches TV, he never gets a break from them and they make him feel like he is going crazy  As his girlfriend, I am extremely concerned that he cannot get relief from these thoughts and that the therapists he is seeing are unable to help him with his problems  Therefore, I am taking initiative to try and help him find better therapy options, because I want to see him someone who can better help him get to the bottom of things and help him with the challenges he is facing  He really needs an advocate that will help him go deep to figure things out and not just assume therapies are working well, without seeing changes or getting supporting feedback from him in that regard 
Here are some questions I am trying to ask in advance to find the right people to help us with this  As you may know, insurance for these therapies are not often available  We don’t have a lot of money to go from therapist to therapist to find the right person and are hoping prescreening will help 
I recently downloaded your e-book and listened to your talks and your information is by far the most helpful I have been able to find to date  It's very accurately describes my situation as an NT wife married to a very probable AS husband  I think you for taking the time to write this and sharing your insights as well as the experiences of many of your clients  It has really helped me understand the last 32 years of our marriage and get a grasp on how to move forward 
One area that is of primary concern to me, that I did not see addressed, is stimming  I believe that is the behavior my husband is showing through constant vocal singing, repetition of words, shouting out, as well as slapping himself in the chest and general nervous activity  It is very loud and disruptive to our household and it is often a relief when he is not at home  I think there may be a level of Tourette's syndrome as well 
I did some searches on the Internet and could not find anything that really describes his behavior  Most of what I found was flapping or children's behavior  I understand that it is a release of nervous tension but I am really trying to find some strategies to help him stop this behavior as it is extremely frustrating and builds my resentment in dealing with it daily  A lot of it is embarrassing as well and sounds childish to me 
He usually does this when close family members are around and will reign himself in if he is around other people besides us  When we are home it is constant  He also has a lot of anger, mostly at himself, and blows up at unimportant things, it is as if he has a ton of negative energy inside him that need to get out and stimming is one outlet 
I will try to build my acceptance of it, but I also would just like him to stop especially the loudest and most annoying portions  Would you have any resources you could point me to?



ground_truth: A study on the effects of Brazilian Jiu Jitsu and psychotherapy on people with autism.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What is the relationship between the maximum velocity and the amplitude of the blob or depletion?

Read the following text and answer briefly.

Context 2: \section{Model equations} \label{sec:equations}

In drift-fluid models the continuity equation
\begin{align}
 \frac{\partial n}{\partial t} + \nabla\cdot\left( n \vec u_E  \right) &= 0 \label{eq:generala} 
\end{align}
describes the dynamics of the electron density $n$  Here
$\vec u_E := (\hat{\vec b} \times \nabla \phi)/B$ gives the electric drift
velocity in a magnetic field $\vec B := B \hat{\vec b}$ and an electric
potential $\phi$  We neglect contributions of the diamagnetic drift~\cite{Kube2016} 




Equation~\eqref{eq:generala} is closed by invoking quasineutrality, i e  the divergence of the ion polarization, 
the electron diamagnetic and the gravitational drift currents must vanish
\begin{align}
  \nabla\cdot\left( \frac{n}{\Omega} \left( \frac{\partial}{\partial t} 
  + \vec u_E \cdot\nabla  \right)\frac{\nabla_\perp \phi}{B}  + n\vec u_d - n\vec u_g\right) &=0
    
 
 
  \label{eq:generalb}
\end{align}
Here we denote 
$\nabla_\perp\phi/B := - \hat{\vec b} \times \vec u_E$, 
the electron diamagnetic drift
$\vec u_d := - T_e(\hat{\vec b} \times\nabla n ) /enB$
with the electron temperature $T_e$,
the ion gravitational drift velocity  
$\vec u_g := m_i \hat{\vec b} \times \vec g /B$
with ion mass $m_i$, and the ion gyro-frequency
$\Omega := eB/m_i$ 

Combining Eq ~\eqref{eq:generalb} with Eq ~\eqref{eq:generala} yields
\begin{align}
 \frac{\partial \rho}{\partial t} + \nabla\cdot\left( \rho\vec u_E \right) + \nabla \cdot\left( n(\vec u_\psi + \vec u_d + \vec u_g) \right) &= 0\label{eq:vorticity}
\end{align}
with the polarization charge density 
$\rho = \nabla\cdot( n\nabla_\perp \phi / \Omega B)$ 
and
$\vec u_\psi := \hat{\vec b}\times \nabla\psi /B$ 
with 
$\psi:= m_i\vec u_E^2 /2e$ 
We exploit this form of Eq ~\eqref{eq:generalb} in our numerical simulations 

Equations~\eqref{eq:generala} and \eqref{eq:generalb} respectively \eqref{eq:vorticity} have several invariants 
First, in Eq ~\eqref{eq:generala} the relative particle number 
$M(t) := \int \mathrm{dA}\, (n-n_0)$ is conserved over time
$\d M(t)/\d t = 0$  
Furthermore, we integrate 
$( T_e(1+\ln n) -T_e \ln B)\partial_t n$
as well as
$-e\phi \partial_t\rho - (m_i\vec u_E^2/2+gm_ix - T_e\ln B)\partial_t n$ 
over the domain to get, disregarding boundary contributions,
\begin{align}
  \frac{\d}{\d t}\left[T_eS(t) + H(t) \right] = 0, \label{eq:energya}\\ 
    \frac{\d}{\d t} \left[ E(t) - G(t) - H(t)\right] =  0,
    \label{eq:energyb}
\end{align}
where we define 
the entropy
$S(t):=\int \mathrm{dA}\, [n\ln(n/n_0) - (n-n_0)]$,  
the kinetic energy 
$E(t):=m_i \int \mathrm{dA}\, n\vec u_E^2/2$ 
and the potential energies
$G(t) := m_i g\int \mathrm{dA}\, x(n-n_0)$
and
$H(t) := T_e\int \mathrm{dA}\, (n-n_0) \ln (B^{-1})$ 
Note that $n\ln( n/n_0) - n + n_0 \approx (n-n_0)^2/2$ for $|(n-n_0)/n_0| \ll 1$ and $S(t)$ thus reduces to the 
local entropy form in Reference~\cite{Kube2016}  

We now set up a gravitational field $\vec g = g\hat x$ and a constant homogeneous background
magnetic field $\vec B = B_0 \hat z$ in a Cartesian coordinate system 
Then the divergences of the electric and gravitational drift velocities $\nabla\cdot\vec u_E$ and $\nabla\cdot\vec u_g$
and the diamagnetic current $\nabla\cdot(n\vec u_d)$ vanish, which makes the 
flow incompressible  Furthermore, the magnetic potential energy vanishes $H(t) = 0$ 

In a second system we model the inhomogeneous magnetic field present in tokamaks as
$\vec B := B_0 (1+ x/R_0)^{-1}\hat z$ and neglect the gravitational drift $\vec u_g = 0$ 
Then, the potential energy $G(t) = 0$  
Note that 
$H(t) = m_i \ensuremath{C_\mathrm{s}}^2/R_0\int\mathrm{dA}\, x(n-n_0) +\mathcal O(R_0^{-2}) $
reduces to $G(t)$ with the effective gravity $g_\text{eff}:= \ensuremath{C_\mathrm{s}}^2/R_0$ with $\ensuremath{C_\mathrm{s}}^2 := T_e/m_i$  
For the rest of this letter we treat $g$ and $g_\text{eff}$ as well as $G(t)$ and $H(t)$ on the same footing 
The magnetic field inhomogeneity thus entails compressible flows, which is 
the only difference to the model describing dynamics in a homogeneous magnetic field introduced above  
Since both $S(t)\geq 0$ and $E(t)\geq 0$ we further derive from Eq ~\eqref{eq:energya} and Eq ~\eqref{eq:energyb} that the kinetic energy
is bounded by $E(t) \leq T_eS(t) + E(t) = T_e S(0)$; a feature absent from the gravitational system with 
incompressible flows, where $S(t) = S(0)$  

We now show that the invariants Eqs ~\eqref{eq:energya} and \eqref{eq:energyb} present restrictions on the velocity and
acceleration of plasma blobs  
First, we define the blobs' center of mass (COM) via $X(t):= \int\mathrm{dA}\, x(n-n_0)/M$ and 
its COM velocity as $V(t):=\d X(t)/\d t$  
The latter is proportional to the total radial particle flux~\cite{Garcia_Bian_Fundamensky_POP_2006, Held2016a} 
We assume
that $n>n_0$ and $(n-n_0)^2/2 \leq [ n\ln (n/n_0) - (n-n_0)]n $ to show for both systems 
\begin{align}
  (MV)^2 &= \left( \int \mathrm{dA}\, n{\phi_y}/{B} \right)^2
  = \left( \int \mathrm{dA}\, (n-n_0){\phi_y}/{B} \right)^2\nonumber\\
 
&\leq 2 \left( \int \mathrm{dA}\, \left[n\ln (n/n_0) -(n-n_0)\right]^{1/2}\sqrt{n}{\phi_y}/{B}\right)^2\nonumber\\
 
  &\leq 4 S(0) E(t)/m_i 
 
  \label{eq:inequality}
\end{align}
Here we use the Cauchy-Schwartz inequality and 
$\phi_y:=\partial\phi/\partial y$  
Note that although we derive the inequality Eq ~\eqref{eq:inequality} only for amplitudes $\triangle n >0$  we assume that the results also hold for depletions  This is justified by our numerical results later in this letter  
If we initialize our density field with a seeded blob of radius $\ell$ and amplitude $\triangle n$ as 
\begin{align}
  n(\vec x, 0) &= n_0 + \triangle n \exp\left( -\frac{\vec x^2}{2\ell^2} \right), \label{eq:inita}
 
 
\end{align}
and  
$\phi(\vec x, 0 ) = 0$,
we immediately have $M := M(0) = 2\pi \ell^2 \triangle n$, $E(0) = G(0) = 0$ and 
$S(0) = 2\pi \ell^2 f(\triangle n)$, where $f(\triangle n)$ captures the amplitude dependence of 
the integral for $S(0)$  

The acceleration for both incompressible and compressible flows can be estimated
by assuming a linear acceleration $V=A_0t$ and $X=A_0t^2/2$~\cite{Held2016a} and using 
$E(t) = G(t) = m_igMX(t)$ in Eq ~\eqref{eq:inequality}
\begin{align}
  \frac{A_0}{g} =  \mathcal Q\frac{2S(0)}{M} \approx \frac{\mathcal Q}{2} \frac{\triangle n }{n_0+2\triangle n/9} 
  \label{eq:acceleration}
\end{align}
Here, we use the Pad\'e approximation of order $(1/1)$ of $2S(0)/M $
and define a model parameter $\mathcal Q$ with $0<\mathcal Q\leq1$ to be determined by numerical simulations 
Note that the Pad\'e approximation is a better approximation than a simple 
truncated Taylor expansion especially for large relative amplitudes of order unity 
Eq ~\eqref{eq:acceleration} predicts that $A_0/g\sim \triangle n/n_0$ for small 
amplitudes $|\triangle n/n_0| < 1$ and $A_0 \sim g $ for very large amplitudes $\triangle n /n_0 \gg 1$, 
which confirms the predictions in~\cite{Pecseli2016} and reproduces the limits discussed in~\cite{Angus2014} 

As pointed out earlier for compressible flows Eq ~\eqref{eq:inequality} can be further estimated
\begin{align}
  (MV)^2  \leq 4 T_eS(0)^2/m_i  
  \label{}
\end{align}
We therefore have a restriction on the maximum COM velocity for compressible flows, which is absent for incompressible flows
\begin{align}
  \frac{\max |V|}{\ensuremath{C_\mathrm{s}}} = {\mathcal Q}\frac{2S(0)}{M} \approx \frac{\mathcal Q}{2} \frac{|\triangle n| }{n_0+2/9 \triangle n } \approx \frac{\mathcal Q}{2} \frac{|\triangle n|}{n_0} 
  \label{eq:linear}
\end{align}
For $|\triangle n /n_0|< 1$ Eq ~\eqref{eq:linear} reduces to the linear scaling derived in~\cite{Kube2016}  
Finally, a scale analysis of Eq ~\eqref{eq:vorticity} shows that~\cite{Ott1978, Garcia2005, Held2016a}
\begin{align}
  \frac{\max |V|}{\ensuremath{C_\mathrm{s}}} = \mathcal R \left( \frac{\ell}{R_0}\frac{|\triangle n|}{n_0} \right)^{1/2} 
  \label{eq:sqrt}
\end{align}
This equation predicts a square root dependence of the center of mass velocity 
on amplitude and size  





We now propose a simple phenomenological model that captures the essential dynamics
of blobs and depletions in the previously stated systems  More specifically 
the model reproduces the acceleration Eq ~\eqref{eq:acceleration} with and without
Boussinesq approximation, the square root scaling for the COM velocity 
Eq ~\eqref{eq:sqrt} for incompressible flows as well as the relation between the 
square root scaling Eq ~\eqref{eq:sqrt} and the linear scaling 
Eq ~\eqref{eq:linear} for compressible flows  
The basic idea is that the COM of blobs behaves like 
the one of an infinitely long plasma column immersed in an ambient plasma  
The dynamics of this column reduces to the one of a two-dimensional ball 
This idea is similar to the analytical ``top hat'' density solution for
blob dynamics recently studied in~\cite{Pecseli2016} 
The ball is subject to buoyancy as well as linear and nonlinear friction
\begin{align}
  M_{\text{i}} \frac{d V}{d t} = (M_{\text{g}} - M_\text{p}) g - c_1 V  - \mathrm{sgn}(V ) \frac{1}{2}c_2 V^2 
  \label{eq:ball}
\end{align}
The gravity $g$ has a positive sign in the coordinate system; sgn$(f)$ is the sign function  
The first term on the right hand side is the buoyancy, where 
$M_{\text{g}} := \pi \ell^2 (n_0 + \mathcal Q \triangle n/2)$ 
is the gravitational mass of the ball with radius $\ell$ and 
$M_\mathrm{p} := n_0 \pi \ell^2 $ 
is the mass of the displaced ambient plasma 
Note that if $\triangle n<0$ the ball represents a depletion and the buoyancy term has a negative sign, i e  the depletion will rise  
We introduce an inertial mass 
$M_{\text{i}} := \pi\ell^2 (n_0 +2\triangle n/9)$ 
different from the gravitational mass $M_{\text{g}}$ in order to 
recover the initial acceleration in Eq ~\eqref{eq:acceleration}  
We interpret the parameters $\mathcal Q$ and $2/9$ as geometrical factors 
that capture the difference of the actual blob form from the idealized
``top hat'' solution  
Also note that the Boussinesq approximation appears in the model as a neglect of inertia, $M_{\text{i}} = \pi\ell^2n_0$ 

The second term is the linear friction term with coefficient $c_1(\ell)$, which
depends on the size of the ball 
If we disregard the nonlinear friction, $c_2=0$, Eq ~\eqref{eq:ball} directly yields a 
maximum velocity $c_1V^*=\pi \ell^2 n g \mathcal Q\triangle n/2$ 
From our previous considerations $\max V/\ensuremath{C_\mathrm{s}}=\mathcal Q \triangle n /2n_0$, we thus identify 
\begin{align}
  c_1 = \pi\ell^2 n_0 g/\ensuremath{C_\mathrm{s}}  
  \label{}
\end{align}
The linear friction coefficient thus depends on the gravity and the size of the
ball  

The last term in \eqref{eq:ball} is the nonlinear friction  The sign of the force depends on whether
the ball rises or falls in the ambient plasma  
If we disregard linear friction $c_1=0$, we have the maximum velocity 
$V^*= \sigma(\triangle n)\sqrt{\pi \ell^2|\triangle n| g\mathcal Q/c_2}$, 
which must equal 
$\max V= \sigma(\triangle n) \mathcal R \sqrt{g \ell |\triangle n/n_0|}$ 
and thus
\begin{align}
  c_2 = {\mathcal Q\pi n_0\ell }/{\mathcal R^2} 
  \label{}
\end{align}
Inserting $c_1$ and $c_2$ into Eq ~\eqref{eq:ball}
we can derive the maximum absolute velocity in the form 
\begin{align}
  \frac{\max |V|}{\ensuremath{C_\mathrm{s}}} = 
        \left(\frac{\mathcal R^2}{\mathcal Q}\right) \frac{\ell}{R_0} \left( 
        \left({1+\left( \frac{\mathcal Q}{\mathcal R} \right)^{2} \frac{|\triangle n|/n_0 }{\ell/R_0}}\right)^{1/2}-1 \right)
  \label{eq:vmax_theo}
\end{align}
and thus have a concise expression for $\max |V|$ that captures both the linear
scaling \eqref{eq:linear} as well as the square root scaling \eqref{eq:sqrt} 
With Eq ~\eqref{eq:acceleration} and Eq ~\eqref{eq:sqrt} respectively Eq ~\eqref{eq:vmax_theo} we 
finally arrive at an analytical expression for the time at which the maximum velocity is reached via 
$t_{\max V} \sim \max V/A_0$  Its inverse $\gamma:=t_{\max V}^{-1}$ gives the
global interchange growth rate, for which an empirical expression was
presented in Reference~\cite{Held2016a} 


We use the open source library FELTOR 
to simulate 
Eqs ~\eqref{eq:generala} and \eqref{eq:vorticity} with and without 
drift compression 
For numerical stabilty we added small diffusive terms on the right hand 
sides of the equations 
The discontinuous Galerkin methods employ three polynomial coefficients and a minimum of $N_x=N_y=768$ grid cells  The box size is $50\ell$ in order to mitigate 
influences of the finite box size on the blob dynamics  
Moreover, we used the invariants in Eqs  \eqref{eq:energya} and \eqref{eq:energyb} as consistency tests to verify the code and repeated simulations 
also in a gyrofluid model  
No differences to the results presented here were found  
Initial perturbations on the particle density field are given by Eq ~\eqref{eq:inita},
where the perturbation amplitude $\triangle n/n_0$ was chosen between $10^{-3}$ and $20$ for blobs and $-10^0$ and $ -10^{-3}$ for depletions  
Due to computational reasons we show results only for $\triangle n/n_0\leq 20$  


For compressible flows we consider two different cases $\ell/R_0 = 10^{-2}$ and
$\ell /R_0 = 10^{-3}$  
 For incompressible flows Eq ~\eqref{eq:generala} and \eqref{eq:vorticity}
 can be normalized such that the blob radius is absent from the equations~\cite{Ott1978, Kube2012}  
 The simulations of incompressible flows can thus be used for both sizes  
The numerical code as well as input parameters and output data can be found 
in the supplemental dataset to this contribution~\cite{Data2017} 

\begin{figure}[htb]
    \includegraphics[width=\columnwidth]{com_blobs}
    \caption{
      The maximum radial COM velocities of blobs for compressible and incompressible flows are shown  
      The continuous lines show Eq ~\eqref{eq:vmax_theo} while the 
      dashed line shows the square root scaling Eq ~\eqref{eq:sqrt} with 
      $\mathcal Q = 0 32$ and $\mathcal R=0 85$ 
    }
    \label{fig:com_blobs}
\end{figure}
In Fig ~\ref{fig:com_blobs} we plot the maximum COM velocity for blobs 
with and without drift compression 
For incompressible flows blobs follow the square root scaling almost 
perfectly  Only at very large amplitudes velocities are slightly below
the predicted values  
For small amplitudes we observe that the compressible blobs follow
a linear scaling  When the amplitudes increase there is a transition to the
square root scaling at around $\triangle n/n_0 \simeq 0 5$ for 
$\ell/R_0=10^{-2}$ and $\triangle n/n_0 \simeq 0 05$ for $\ell/R_0=10^{-3}$, which is consistent with Eq ~\eqref{eq:vmax_theo} and Reference~\cite{Kube2016}  
In the transition regions the simulated velocities are slightly larger than the predicted ones from Eq ~\eqref{eq:vmax_theo} 
Beyond these amplitudes
the velocities of compressible and incompressible blobs align  

\begin{figure}[htb]
    \includegraphics[width=\columnwidth]{com_holes}
    \caption{
      The maximum radial COM velocities of depletions for compressible and incompressible flows are shown  
      The continuous lines show Eq ~\eqref{eq:vmax_theo} while the 
      dashed line shows the square root scaling Eq ~\eqref{eq:sqrt} with 
      $\mathcal Q = 0 32$ and $\mathcal R=0 85$ 
      Note that small amplitudes are on the right and amplitudes close to unity are on the left side 
  }
    \label{fig:com_depletions}
\end{figure}
In Fig ~\ref{fig:com_depletions} we show the maximum radial COM velocity 
for depletions instead of blobs 
For relative amplitudes below $|\triangle n|/n_0 \simeq 0 5$ (right of unity in the plot) the velocities
coincide with the corresponding blob velocities in Fig ~\ref{fig:com_blobs}  
 For amplitudes larger than $|\triangle n|/n_0\simeq 0 5$ the 
velocities follow the square root scaling 
We observe that for plasma depletions beyond $90$ percent the velocities 
in both systems reach a constant value that is very well predicted by the
square root scaling  

\begin{figure}[htb]
    \includegraphics[width=\columnwidth]{acc_blobs}
    \caption{
      Average acceleration of blobs for compressible and incompressible flows are shown 
      The continuous line shows the acceleration in Eq ~\eqref{eq:acceleration} 
      with $\mathcal Q=0 32$
      while the dashed line is a linear reference line, which corresponds to the Boussinesq approximation  
  }
    \label{fig:acc_blobs}
\end{figure}
In Fig ~\ref{fig:acc_blobs} we show the average acceleration of blobs 
for compressible and incompressible flows computed
by dividing the maximum velocity $\max V$ by the time  
to reach this velocity $t_{\max V}$  
We compare the simulation results
to the theoretical predictions Eq ~\eqref{eq:acceleration} of our model with and without inertia  
The results of the compressible and incompressible systems coincide and fit very
well to our theoretical values  
For amplitudes larger than unity the acceleration deviates significantly from the prediction with Boussinesq approximation 

\begin{figure}[htb]
    \includegraphics[width=\columnwidth]{acc_holes}
    \caption{
      Average acceleration of depletions for compressible and incompressible flows are shown 
      The continuous line shows the acceleration in Eq ~\eqref{eq:acceleration} 
      with $\mathcal Q=0 32$
      while the dashed line is a linear reference line, which corresponds to the Boussinesq approximation  
    }
    \label{fig:acc_depletions}
\end{figure}
In Fig ~\ref{fig:acc_depletions} we show the simulated acceleration of depletions in the
compressible and the incompressible systems  We compare the simulation results
to the theoretical predictions Eq ~\eqref{eq:acceleration} of our model with and without inertia 
Deviations from our theoretical prediction Eq ~\eqref{eq:acceleration} are visible for amplitudes smaller than $\triangle n/n_0 \simeq -0 5$ (left of unity in the plot)  The relative deviations are small at around $20$ percent  
As in Fig ~\ref{fig:com_depletions} the acceleration reaches a constant values
for plasma depletions of more than $90$ percent 
Comparing Fig ~\ref{fig:acc_depletions} to Fig ~\ref{fig:acc_blobs} the asymmetry between blobs and depletions becomes 
apparent  While the acceleration of blobs is reduced for large 
amplitudes compared to a linear dependence the acceleration 
of depletions is increased  In the language of our simple buoyancy 
model the inertia of depletions is reduced but increased for blobs  



In conclusion  
  we discuss the dynamics of seeded blobs and depletions in a 
  compressible and an incompressible system 
  With only two fit parameters our theoretical results reproduce the 
  numerical COM velocities and accelerations over five orders of magnitude 
  We derive the amplitude dependence of the acceleration of blobs and depletions from 
  the conservation laws of our systems in Eq ~\eqref{eq:acceleration}  
  From the same inequality a linear regime is derived in the compressible system for 
  ratios of amplitudes to sizes smaller than a critical value 
   In this regime 
  the blob and depletion velocity depends linearly on the initial amplitude and 
  is independent of size  The regime is absent from the system with incompressible flows 
  Our theoretical results are verified by numerical simulations for all 
  amplitudes that are relevant in magnetic fusion devices 
  Finally, we suggest a new empirical blob model that captures the detailed dynamics of more complicated models  
  The Boussinesq approximation is clarified as the absence of inertia and a thus altered acceleration of blobs and depletions 
  The maximum blob velocity is not altered by the Boussinesq approximation 

The authors were supported with financial subvention from the Research Council of Norway under grant
240510/F20  M W  and M H  were supported by the Austrian Science Fund (FWF) Y398   The computational
results presented have been achieved in part using the Vienna Scientific Cluster (VSC)  Part of this work was performed on the Abel Cluster, owned by the University of Oslo and the Norwegian metacenter
for High Performance Computing (NOTUR), and operated by the Department for Research Computing at USIT,
the University of Oslo IT-department 
This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053  The views and opinions expressed herein do not necessarily reflect those of the European Commission 
Context 3: Vitamin K - Wikipedia
(Redirected from Vitamin k)
This article needs more medical references for verification or relies too heavily on primary sources  Please review the contents of the article and add the appropriate references if you can  Unsourced or poorly sourced material may be challenged and removed  (November 2015)
This article is about the family of vitamers  For vitamin K1 the form usually used as a supplement, see Phytomenadione 
Vitamin K structures  MK-4 and MK-7 are both subtypes of K2 
Vitamin K deficiency, Warfarin overdose
Vitamin K is a group of structurally similar, fat-soluble vitamins the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation and which the body also needs for controlling binding of calcium in bones and other tissues  The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise  Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs  Low levels of vitamin K also weaken bones and promote calcification of arteries and other soft tissues[citation needed] 
Chemically, the vitamin K family comprises 2-methyl-1,4-naphthoquinone (3-) derivatives  Vitamin K includes two natural vitamers: vitamin K1 and vitamin K2 [1] Vitamin K2, in turn, consists of a number of related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms 
Vitamin K1, also known as phylloquinone, is made by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis  It may be thought of as the plant form of vitamin K  It is active as a vitamin in animals and performs the classic functions of vitamin K, including its activity in the production of blood-clotting proteins  Animals may also convert it to vitamin K2 
Bacteria in the gut flora can also convert K1 into vitamin K2  In addition, bacteria typically lengthen the isoprenoid side chain of vitamin K2 to produce a range of vitamin K2 forms, most notably the MK-7 to MK-11 homologues of vitamin K2  All forms of K2 other than MK-4 can only be produced by bacteria, which use these forms in anaerobic respiration  The MK-7 and other bacterially derived forms of vitamin K2 exhibit vitamin K activity in animals, but MK-7's extra utility over MK-4, if any, is unclear and is a matter of investigation 
Three synthetic types of vitamin K are known: vitamins K3, K4, and K5  Although the natural K1 and all K2 homologues and synthetic K4 and K5 have proven nontoxic, the synthetic form K3 (menadione) has shown toxicity [2]
1 2 Cardiovascular health
1 4 Coumarin poisoning
4 1 Conversion of vitamin K1 to vitamin K2
4 2 Vitamin K2
6 Absorption and dietary need
7 Dietary reference intake
10 Biochemistry
10 1 Function in animals
10 2 Gamma-carboxyglutamate proteins
10 3 Methods of assessment
10 4 Function in bacteria
11 Injection in newborns
11 3 Controversy
A review of 2014 concluded that there is positive evidence that monotherapy using MK-4, one of the forms of Vitamin K2, reduces fracture incidence in post-menopausal women with osteoporosis, and suggested further research on the combined use of MK-4 with bisphosphonates  In contrast, an earlier review article of 2013 concluded that there is no good evidence that vitamin K supplementation helps prevent osteoporosis or fractures in postmenopausal women [3]
A Cochrane systematic review of 2006 suggested that supplementation with Vitamin K1 and with MK4 reduces bone loss; in particular, a strong effect of MK-4 on incident fractures among Japanese patients was emphasized [4]
A review article of 2016 suggested to consider, as one of several measures for bone health, increasing the intake of foods rich in vitamins K1 and K2 [5]
Cardiovascular health[edit]
Adequate intake of vitamin K is associated with the inhibition of arterial calcification and stiffening,[6] but there have been few interventional studies and no good evidence that vitamin K supplementation is of any benefit in the primary prevention of cardiovascular disease [7]
One 10-year population study, the Rotterdam Study, did show a clear and significant inverse relationship between the highest intake levels of menaquinone (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese) and cardiovascular disease and all-cause mortality in older men and women [8]
Vitamin K has been promoted in supplement form with claims it can slow tumor growth; there is however no good medical evidence that supports such claims [9]
Coumarin poisoning[edit]
Vitamin K is part of the suggested treatment regime for poisoning by rodenticide (coumarin poisoning) [10]
Although allergic reaction from supplementation is possible, no known toxicity is associated with high doses of the phylloquinone (vitamin K1) or menaquinone (vitamin K2) forms of vitamin K, so no tolerable upper intake level (UL) has been set [11]
Blood clotting (coagulation) studies in humans using 45 mg per day of vitamin K2 (as MK-4)[12] and even up to 135 mg per day (45 mg three times daily) of K2 (as MK-4),[13] showed no increase in blood clot risk  Even doses in rats as high as 250 mg/kg, body weight did not alter the tendency for blood-clot formation to occur [14]
Unlike the safe natural forms of vitamin K1 and vitamin K2 and their various isomers, a synthetic form of vitamin K, vitamin K3 (menadione), is demonstrably toxic at high levels  The U S  FDA has banned this form from over-the-counter sale in the United States because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells [2]
Phylloquinone (K1)[15][16] or menaquinone (K2) are capable of reversing the anticoagulant activity of the anticoagulant warfarin (tradename Coumadin)  Warfarin works by blocking recycling of vitamin K, so that the body and tissues have lower levels of active vitamin K, and thus a deficiency of vitamin K 
Supplemental vitamin K (for which oral dosing is often more active than injectable dosing in human adults) reverses the vitamin K deficiency caused by warfarin, and therefore reduces the intended anticoagulant action of warfarin and related drugs [17] Sometimes small amounts of vitamin K are given orally to patients taking warfarin so that the action of the drug is more predictable [17] The proper anticoagulant action of the drug is a function of vitamin K intake and drug dose, and due to differing absorption must be individualized for each patient [citation needed] The action of warfarin and vitamin K both require two to five days after dosing to have maximum effect, and neither warfarin or vitamin K shows much effect in the first 24 hours after they are given [18]
The newer anticoagulants dabigatran and rivaroxaban have different mechanisms of action that do not interact with vitamin K, and may be taken with supplemental vitamin K [19][20]
Vitamin K2 (menaquinone)  In menaquinone, the side chain is composed of a varying number of isoprenoid residues  The most common number of these residues is four, since animal enzymes normally produce menaquinone-4 from plant phylloquinone 
A sample of phytomenadione for injection, also called phylloquinone
The three synthetic forms of vitamin K are vitamins K3 (menadione), K4, and K5, which are used in many areas, including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5) [21]
Conversion of vitamin K1 to vitamin K2[edit]
Vitamin K1 (phylloquinone) – both forms of the vitamin contain a functional naphthoquinone ring and an aliphatic side chain  Phylloquinone has a phytyl side chain 
The MK-4 form of vitamin K2 is produced by conversion of vitamin K1 in the testes, pancreas, and arterial walls [22] While major questions still surround the biochemical pathway for this transformation, the conversion is not dependent on gut bacteria, as it occurs in germ-free rats[23][24] and in parenterally-administered K1 in rats [25][26] In fact, tissues that accumulate high amounts of MK-4 have a remarkable capacity to convert up to 90% of the available K1 into MK-4 [27][28] There is evidence that the conversion proceeds by removal of the phytyl tail of K1 to produce menadione as an intermediate, which is then condensed with an activated geranylgeranyl moiety (see also prenylation) to produce vitamin K2 in the MK-4 (menatetrione) form [29]
Vitamin K2[edit]
Main article: Vitamin K2
Vitamin K2 (menaquinone) includes several subtypes  The two subtypes most studied are menaquinone-4 (menatetrenone, MK-4) and menaquinone-7 (MK-7) 
Vitamin K1, the precursor of most vitamin K in nature, is a stereoisomer of phylloquinone, an important chemical in green plants, where it functions as an electron acceptor in photosystem I during photosynthesis  For this reason, vitamin K1 is found in large quantities in the photosynthetic tissues of plants (green leaves, and dark green leafy vegetables such as romaine lettuce, kale and spinach), but it occurs in far smaller quantities in other plant tissues (roots, fruits, etc )  Iceberg lettuce contains relatively little  The function of phylloquinone in plants appears to have no resemblance to its later metabolic and biochemical function (as "vitamin K") in animals, where it performs a completely different biochemical reaction 
Vitamin K (in animals) is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate (Gla) residues  The modified residues are often (but not always) situated within specific protein domains called Gla domains  Gla residues are usually involved in binding calcium, and are essential for the biological activity of all known Gla proteins [30]
At this time[update], 17 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:
Blood coagulation: prothrombin (factor II), factors VII, IX, and X, and proteins C, S, and Z[31]
Bone metabolism: osteocalcin, also called bone Gla protein (BGP), matrix Gla protein (MGP),[32] periostin,[33] and the recently discovered Gla-rich protein (GRP) [34][35]
Vascular biology: growth arrest-specific protein 6 (Gas6)[36]
Unknown function: proline-rich γ-carboxyglutamyl proteins (PRGPs) 1 and 2, and transmembrane γ-carboxy glutamyl proteins (TMGs) 3 and 4 [37]
Like other lipid-soluble vitamins (A, D and E), vitamin K is stored in the fatty tissue of the human body 
Absorption and dietary need[edit]
Previous theory held that dietary deficiency is extremely rare unless the small intestine was heavily damaged, resulting in malabsorption of the molecule  Another at-risk group for deficiency were those subject to decreased production of K2 by normal intestinal microbiota, as seen in broad spectrum antibiotic use [38] Taking broad-spectrum antibiotics can reduce vitamin K production in the gut by nearly 74% in people compared with those not taking these antibiotics [39] Diets low in vitamin K also decrease the body's vitamin K concentration [40] Those with chronic kidney disease are at risk for vitamin K deficiency, as well as vitamin D deficiency, and particularly those with the apoE4 genotype [41] Additionally, in the elderly there is a reduction in vitamin K2 production [42]
The National Academy of Medicine (NAM) updated an estimate of what constitutes an adequate intake (AI) for vitamin K in 2001  The NAM does not distinguish between K1 and K2 – both are counted as vitamin K  At that time there was not sufficient evidence to set the more rigorous estimated average requirement (EAR) or recommended dietary allowance (RDA) given for most of the essential vitamins and minerals  The current daily AIs for vitamin K for adult women and men are 90 μg and 120 μg respectively  The AI for pregnancy and lactation is 90 μg  For infants up to 12 months the AI is 2–2 5 μg, and for children aged 1 to 18 years the AI increases with age from 30 to 75 μg  As for safety, the FNB also sets tolerable upper intake levels (known as ULs) for vitamins and minerals when evidence is sufficient  In the case of vitamin K no UL is set, as evidence for adverse effects is not sufficient  Collectively EARs, RDAs, AIs and ULs are referred to as dietary reference intakes [43] The European Food Safety Authority reviewed the same safety question and did not set an UL [44]
For U S  food and dietary supplement labeling purposes, the amount in a serving is expressed as a percentage of daily value (%DV)  For vitamin K labeling purposes the daily value was 80 μg, but as of May 2016 it has been revised upwards to 120 μg  A table of the pre-change adult daily values is provided at reference daily intake  Food and supplement companies have until 28 July 2018 to comply with the change 
See also: Vitamin K2 § Dietary sources
K1 (μg)[45]
Kale, cooked
Collards, cooked
Collards, raw
Swiss chard, cooked
Swiss chard, raw
Turnip greens, raw
Romaine lettuce, raw
Table from "Important information to know when you are taking: Warfarin (Coumadin) and Vitamin K", Clinical Center, National Institutes of Health Drug Nutrient Interaction Task Force [46]
Vitamin K1 is found chiefly in leafy green vegetables such as dandelion greens (which contain 778 4 μg per 100 g, or 741% of the recommended daily amount), spinach, swiss chard, lettuce and Brassica vegetables (such as cabbage, kale, cauliflower, broccoli, and brussels sprouts) and often the absorption is greater when accompanied by fats such as butter or oils; some fruits, such as avocados, kiwifruit and grapes, are also high in vitamin K  By way of reference, two tablespoons of parsley contains 153% of the recommended daily amount of vitamin K [47] Some vegetable oils, notably soybean oil, contain vitamin K, but at levels that would require relatively large calorie consumption to meet the USDA-recommended levels [48] colonic bacteria synthesize a significant portion of humans' vitamin K needs; newborns often receive a vitamin K shot at birth to tide them over until their colons become colonized at five to seven days of age from the consumption of breast milk 
The tight binding of vitamin K1 to thylakoid membranes in chloroplasts makes it less bioavailable  For example, cooked spinach has a 5% bioavailability of phylloquinone, however, fat added to it increases bioavailability to 13% due to the increased solubility of vitamin K in fat [49]
Main article: Vitamin K deficiency
Average diets are usually not lacking in vitamin K, and primary deficiency is rare in healthy adults  Newborn infants are at an increased risk of deficiency  Other populations with an increased prevalence of vitamin K deficiency include those who suffer from liver damage or disease (e g  alcoholics), cystic fibrosis, or inflammatory bowel diseases, or have recently had abdominal surgeries  Secondary vitamin K deficiency can occur in people with bulimia, those on stringent diets, and those taking anticoagulants  Other drugs associated with vitamin K deficiency include salicylates, barbiturates, and cefamandole, although the mechanisms are still unknown  Vitamin K1 deficiency can result in coagulopathy, a bleeding disorder [50]Symptoms of K1 deficiency include anemia, bruising, nosebleeds and bleeding of the gums in both sexes, and heavy menstrual bleeding in women 
Osteoporosis[51][52] and coronary heart disease[53][54] are strongly associated with lower levels of K2 (menaquinone)  Vitamin K2 (as menaquinones MK-4 through MK-10) intake level is inversely related to severe aortic calcification and all-cause mortality [8]
Function in animals[edit]
Mechanism of action of vitamin K1 
The function of vitamin K2 in the animal cell is to add a carboxylic acid functional group to a glutamate (Glu) amino acid residue in a protein, to form a gamma-carboxyglutamate (Gla) residue  This is a somewhat uncommon posttranslational modification of the protein, which is then known as a "Gla protein"  The presence of two −COOH (carboxylic acid) groups on the same carbon in the gamma-carboxyglutamate residue allows it to chelate calcium ions  The binding of calcium ions in this way very often triggers the function or binding of Gla-protein enzymes, such as the so-called vitamin K-dependent clotting factors discussed below 
Within the cell, vitamin K undergoes electron reduction to a reduced form called vitamin K hydroquinone, catalyzed by the enzyme vitamin K epoxide reductase (VKOR) [55] Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla; this enzyme is called gamma-glutamyl carboxylase[56][57] or the vitamin K-dependent carboxylase  The carboxylation reaction only proceeds if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time  The carboxylation and epoxidation reactions are said to be coupled  Vitamin K epoxide is then reconverted to vitamin K by VKOR  The reduction and subsequent reoxidation of vitamin K coupled with carboxylation of Glu is called the vitamin K cycle [58] Humans are rarely deficient in vitamin K1 because, in part, vitamin K1 is continuously recycled in cells [59]
Warfarin and other 4-hydroxycoumarins block the action of VKOR [60] This results in decreased concentrations of vitamin K and vitamin K hydroquinone in tissues, such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient  This results in the production of clotting factors with inadequate Gla  Without Gla on the amino termini of these factors, they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury  As it is impossible to predict what dose of warfarin will give the desired degree of clotting suppression, warfarin treatment must be carefully monitored to avoid overdose 
Gamma-carboxyglutamate proteins[edit]
Main article: Gla domain
The following human Gla-containing proteins ("Gla proteins") have been characterized to the level of primary structure: blood coagulation factors II (prothrombin), VII, IX, and X, anticoagulant proteins C and S, and the factor X-targeting protein Z  The bone Gla protein osteocalcin, the calcification-inhibiting matrix Gla protein (MGP), the cell growth regulating growth arrest specific gene 6 protein (Gas6), and the four transmembrane Gla proteins (TMGPs), the function of which is at present unknown  Gas6 can function as a growth factor to activate the Axl receptor tyrosine kinase and stimulate cell proliferation or prevent apoptosis in some cells  In all cases in which their function was known, the presence of the Gla residues in these proteins turned out to be essential for functional activity 
Gla proteins are known to occur in a wide variety of vertebrates: mammals, birds, reptiles, and fish  The venom of a number of Australian snakes acts by activating the human blood-clotting system  In some cases, activation is accomplished by snake Gla-containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones, leading to unwanted and potentially deadly clotting 
Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus [61] These snails produce a venom containing hundreds of neuroactive peptides, or conotoxins, which is sufficiently toxic to kill an adult human  Several of the conotoxins contain two to five Gla residues [62]
Methods of assessment[edit]
Vitamin K status can be assessed by:
The prothrombin time (PT) test measures the time required for blood to clot  A blood sample is mixed with citric acid and put in a fibrometer; delayed clot formation indicates a deficiency  This test is insensitive to mild deficiency, as the values do not change until the concentration of prothrombin in the blood has declined by at least 50% [63]
Undercarboxylated prothrombin (PIVKA-II); in a study of 53 newborns, found "PT (prothrombin time) is a less sensitive marker than PIVKA II",[64] and as indicated above, PT is unable to detect subclinical deficiencies that can be detected with PIVKA-II testing 
Plasma phylloquinone was found to be positively correlated with phylloquinone intake in elderly British women, but not men,[65] but an article by Schurgers et al  reported no correlation between FFQ[further explanation needed] and plasma phylloquinone [66]
Urinary γ-carboxyglutamic acid responds to changes in dietary vitamin K intake  Several days are required before any change can be observed  In a study by Booth et al , increases of phylloquinone intakes from 100 μg to between 377 and 417 μg for five days did not induce a significant change  Response may be age-specific [67]
Undercarboxylated osteocalcin (UcOc) levels have been inversely correlated with stores of vitamin K[68] and bone strength in developing rat tibiae  Another study following 78 post-menopausal Korean women found a supplement regimen of vitamins K and D, and calcium, but not a regimen of vitamin D and calcium, was inversely correlated with reduced UcOc levels [69]
Function in bacteria[edit]
Many bacteria, such as Escherichia coli found in the large intestine, can synthesize vitamin K2 (menaquinone-7 or MK-7, up to MK-11),[70] but not vitamin K1 (phylloquinone)  In these bacteria, menaquinone transfers two electrons between two different small molecules, during oxygen-independent metabolic energy production processes (anaerobic respiration) [71] For example, a small molecule with an excess of electrons (also called an electron donor) such as lactate, formate, or NADH, with the help of an enzyme, passes two electrons to menaquinone  The menaquinone, with the help of another enzyme, then transfers these two electrons to a suitable oxidant, such fumarate or nitrate (also called an electron acceptor)  Adding two electrons to fumarate or nitrate converts the molecule to succinate or nitrite plus water, respectively 
Some of these reactions generate a cellular energy source, ATP, in a manner similar to eukaryotic cell aerobic respiration, except the final electron acceptor is not molecular oxygen, but fumarate or nitrate  In aerobic respiration, the final oxidant is molecular oxygen (O2), which accepts four electrons from an electron donor such as NADH to be converted to water  E  coli, as facultative anaerobes, can carry out both aerobic respiration and menaquinone-mediated anaerobic respiration 
Injection in newborns[edit]
The blood clotting factors of newborn babies are roughly 30–60% that of adult values; this may be due to the reduced synthesis of precursor proteins and the sterility of their guts  Human milk contains 1–4 μg/L of vitamin K1, while formula-derived milk can contain up to 100 μg/L in supplemented formulas  Vitamin K2 concentrations in human milk appear to be much lower than those of vitamin K1  Occurrence of vitamin K deficiency bleeding in the first week of the infant's life is estimated at 0 25–1 7%, with a prevalence of 2–10 cases per 100,000 births [72] Premature babies have even lower levels of the vitamin, so they are at a higher risk from this deficiency 
Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, blood transfusions, brain damage, and death  Supplementation can prevent most cases of vitamin K deficiency bleeding in the newborn  Intramuscular administration is more effective in preventing late vitamin K deficiency bleeding than oral administration [73][74]
As a result of the occurrences of vitamin K deficiency bleeding, the Committee on Nutrition of the American Academy of Pediatrics has recommended 0 5–1 mg of vitamin K1 be administered to all newborns shortly after birth [74]
In the UK vitamin K supplementation is recommended for all newborns within the first 24 hours [75] This is usually given as a single intramuscular injection of 1 mg shortly after birth but as a second-line option can be given by three oral doses over the first month [76]
Controversy arose in the early 1990s regarding this practice, when two studies suggested a relationship between parenteral administration of vitamin K and childhood cancer,[77] however, poor methods and small sample sizes led to the discrediting of these studies, and a review of the evidence published in 2000 by Ross and Davies found no link between the two [78] Doctors reported emerging concerns in 2013,[79] after treating children for serious bleeding problems  They cited lack-of newborn vitamin K administration, as the reason that the problems occurred, and recommended that breastfed babies could have an increased risk unless they receive a preventative dose 
In the early 1930s, Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet [80] He initially replicated experiments reported by scientists at the Ontario Agricultural College (OAC) [81] McFarlane, Graham and Richardson, working on the chick feed program at OAC, had used chloroform to remove all fat from chick chow  They noticed that chicks fed only fat-depleted chow developed hemorrhages and started bleeding from tag sites [82] Dam found that these defects could not be restored by adding purified cholesterol to the diet  It appeared that – together with the cholesterol – a second compound had been extracted from the food, and this compound was called the coagulation vitamin  The new vitamin received the letter K because the initial discoveries were reported in a German journal, in which it was designated as Koagulationsvitamin  Edward Adelbert Doisy of Saint Louis University did much of the research that led to the discovery of the structure and chemical nature of vitamin K [83] Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K (K1 and K2) published in 1939  Several laboratories synthesized the compound(s) in 1939 [84]
For several decades, the vitamin K-deficient chick model was the only method of quantifying vitamin K in various foods: the chicks were made vitamin K-deficient and subsequently fed with known amounts of vitamin K-containing food  The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content  Three groups of physicians independently found this: Biochemical Institute, University of Copenhagen (Dam and Johannes Glavind), University of Iowa Department of Pathology (Emory Warner, Kenneth Brinkhous, and Harry Pratt Smith), and the Mayo Clinic (Hugh Butt, Albert Snell, and Arnold Osterberg) [85]
The first published report of successful treatment with vitamin K of life-threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 by Smith, Warner, and Brinkhous [86]
The precise function of vitamin K was not discovered until 1974, when three laboratories (Stenflo et al ,[87] Nelsestuen et al ,[88] and Magnusson et al [89]) isolated the vitamin K-dependent coagulation factor prothrombin (factor II) from cows that received a high dose of a vitamin K antagonist, warfarin  It was shown that, while warfarin-treated cows had a form of prothrombin that contained 10 glutamate (Glu) amino acid residues near the amino terminus of this protein, the normal (untreated) cows contained 10 unusual residues that were chemically identified as γ-carboxyglutamate (Gla)  The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla 
The biochemistry of how vitamin K is used to convert Glu to Gla has been elucidated over the past thirty years in academic laboratories throughout the world 
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^ Whitlon, D  S ; Sadowski, J  A ; Suttie, J  W  (Apr 1978)  "Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition"  Biochemistry  17 (8): 1371–1377  doi:10 1021/bi00601a003  PMID 646989  ^ Terlau, H ; Olivera, B  M  (Jan 2004)  "Conus venoms: a rich source of novel ion channel-targeted peptides"  Physiological Reviews  84 (1): 41–68  doi:10 1152/physrev 00020 2003  PMID 14715910  ^ Buczek, O ; Bulaj, G ; Olivera, BM (Dec 2005)  "Conotoxins and the posttranslational modification of secreted gene products"  Cellular and Molecular Life Sciences  62 (24): 3067–3079  doi:10 1007/s00018-005-5283-0  PMID 16314929  ^ "Prothrombin Time"  WebMD  ^ Dituri, F ; Buonocore, G ; Pietravalle, A ; Naddeo, F ; Cortesi, M; Pasqualetti, P; Tataranno M  L ; R , Agostino (Sep 2012)  "PIVKA-II plasma levels as markers of subclinical vitamin K deficiency in term infants"  Journal of Maternal, Fetal & Neonatal Medicine  25 (9): 1660–1663  doi:10 3109/14767058 2012 657273  PMID 22280352  ^ Thane, C  W ; 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Rhéaume-Bleue, Kate (2012)  Vitamin K2 and the Calcium Paradox  John Wiley & Sons, Canada  ISBN 1-118-06572-7  External links[edit]
"Vitamin K: Another Reason to Eat Your Greens"  v
TPP / ThDP (B1)
FMN, FAD (B2)
NAD+, NADH, NADP+, NADPH (B3)
Coenzyme A (B5)
PLP / P5P (B6)
THFA / H4FA, DHFA / H2FA, MTHF (B9)
AdoCbl, MeCbl (B12)
Phylloquinone (K1), Menaquinone (K2)
non-vitamins
Coenzyme B
Heme / Haem (A, B, C, O)
Molybdopterin/Molybdenum cofactor
THMPT / H4MPT
Fe2+, Fe3+
vitamins: see vitamins
Antihemorrhagics (B02)
(coagulation)
Phytomenadione (K1)
Menadione (K3)
intrinsic: IX/Nonacog alfa
VIII/Moroctocog alfa/Turoctocog alfa
extrinsic: VII/Eptacog alfa
common: X
II/Thrombin
I/Fibrinogen
XIII/Catridecacog
combinations: Prothrombin complex concentrate (II, VII, IX, X, protein C and S)
Carbazochrome
thrombopoietin receptor agonist (Romiplostim
Eltrombopag)
Tetragalacturonic acid hydroxymethylester
Epinephrine/Adrenalone
amino acids (Aminocaproic acid
Aminomethylbenzoic acid)
serpins (Aprotinin
Alfa1 antitrypsin
Camostat) 



ground_truth: The maximum velocity scales with the square root of the amplitude.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What are the symptoms of vitamin K deficiency?

Read the following text and answer briefly.

Context 4: 3$) rises to plasma in about 2 ns \cite{Saquet2012}   

\begin{figure}[h!]
\centering
\includegraphics[width=  49 \textwidth]{SFI_n=49 pdf}
   \caption{Contour plots showing SFI signal as a function the applied field for an $nf(2)$ Rydberg gas with an initial principal quantum number, $n_0=49$   Each frame represents 4,000 SFI traces, sorted by initial Rydberg gas density   Ramp field beginning at 0 and 150 ns (top, left to right), and  300 and 450 ns (bottom) after the $\omega_2$ laser pulse   The two bars of signal most evident at early ramp field delay times represent the field ionization of the $49f(2)$ Rydberg state respectively to NO$^+$ X $^1\Sigma^+$ cation rotational states, $N^+=0$ and 2   The signal waveform extracted near zero applied field represents the growing population of plasma electrons   
   }
\label{fig:SFI}
\end{figure}

Selective field ionization (SFI) probes the spectrum of binding energies in a Rydberg gas   Applied as a function of time after photoexcitation, SFI maps the evolution from a state of selected initial principal quantum number, $n_0$, to plasma \cite{Haenel2017}   Figure \ref{fig:SFI} shows SFI spectra taken at a sequence of delays after the formation of $49f(2)$ Rydberg gases of varying density     

Here, we can see that a $49f(2)$ Rydberg gas with an estimated initial density $\rho_0 = 3 \times 10^{11} ~{\rm cm}^{-3}$ relaxes to plasma on a timescale of about 500 ns   Observations such as these agree well with the predictions of coupled rate-equation calculations   We can understand this variation in relaxation dynamics with $\rho_0$ and $n_0$ quite simply in terms of the corresponding density of prompt Penning electrons these conditions afford to initiate the avalanche to plasma   

Figure \ref{fig:scaled_rise} illustrates this, showing how rise times predicted by coupled rate-equation simulations for a large range of initial densities and principal quantum number match when plotted as a function of time scaled by the ultimate plasma frequency and fraction of prompt Penning electrons   The dashed line gives an approximate account of the scaled rate of avalanche under all conditions of Rydberg gas density and initial principal quantum number in terms of the simple sigmoidal function:

\begin{equation}
\frac{\rho_e}{\rho_0} = \frac{a}{b+e^{-c\tau}},
  \label{scaledEq1}
\end{equation}
where,
\begin{equation}
\tau = t \omega_e P_f^{3/4},
  \label{scaledEq2}
\end{equation}
in which $\omega_e$ is the plasma frequency after avalanche, $P_f$ is the fraction of prompt Penning electrons, and $a = 0 00062$,  $b =   0 00082$ and $c =     0 075$ are empirical coefficients   

\begin{figure}[h!]
\centering
\includegraphics[width=  4 \textwidth]{sim_analytical_density pdf}
   \caption{Rise in fractional electron density as a function of time scaled by the plasma frequency, $\omega_e$ and fraction, $\rho_e(t=0)/\rho_0 = P_f$, of prompt Penning electrons   Simulation results shown for $n_0 = 30$, 50 and 70 with initial densities, $\rho_0 = 10^9,~10^{10},~10^{11},~{\rm and}~10^{12}~{\rm cm}^{-3}$   
   }
\label{fig:scaled_rise}
\end{figure}


\subsection{Evolution to plasma in a Rydberg gas Gaussian ellipsoid}

As outlined above, the local density and principal quantum number together determine the rate at which a Rydberg gas avalanches to plasma   Our experiment crosses a 2 mm wide cylindrically Gaussian molecular beam with a 1 mm diameter TEM$_{00}$ $\omega_1$ laser beam to produce a Gaussian ellipsoidal distribution of molecules excited to the A $^2\Sigma^+$ $v=0, ~N'=0$ intermediate state   A larger diameter $\omega_2$ pulse then drives a second step that forms a Rydberg gas in a single $n_0f(2)$ state with the spatial distribution of the intermediate state   

We model this shaped Rydberg gas as a system of 100 concentric ellipsoidal shells of varying density \cite{haenelCP}   Coupled rate equations within each shell describe the avalanche to plasma   This rate process proceeds from shell to shell with successively longer induction periods, determined by the local density as detailed above   The rising conversion of Rydberg molecules to ions plus neutral dissociation products conserves the particle number in each shell   We assume that local space charge confines electrons to shells, conserving quasi-neutrality   Electrons exchange kinetic energy at the boundaries of each shell, which determines a single plasma electron temperature   

\begin{figure}[h!]
\centering
\includegraphics[width=  5 \textwidth]{shell_model_100}
   \caption{(top frame) Cross-sectional contour diagram in the $x,y$ plane for $z=0$ describing the distribution of ion plus electron density over 100 shells of Gaussian ellipsoid with initial dimensions, $\sigma_x= 0 75$ mm and $\sigma_y= \sigma_z = 0 42$ mm and an initial $n_0 = 50$ Rydberg gas density, $\rho_0 = 2 \times 10^{11}$ cm$^{3}$ after an evolution time of 100 ns   (bottom frame) Curves describing the (dashed) ascending ion and (solid) descending Rydberg gas densities of each shell as functions of evolution time, for $t=20$, 40, 60, 80 and 100 ns   
   }
\label{fig:shell}
\end{figure}

The upper frame of Figure \ref{fig:shell} shows contours of NO$^+$ ion density after 100 ns obtained from a shell-model coupled rate-equation simulation of the avalanche of a Gaussian ellipsoidal Rydberg gas of nitric oxide with a selected initial state, $50f(2)$ and a density of $2 \times 10^{11}$ cm$^{-3}$   Here, we simulate a relaxation that includes channels of predissociation at every Rydberg level and redistributes the energy released to electrons, which determines a uniform rising electron temperature for all shells   

For comparison, the lower frame plots curves describing the ion density of each shell as a function of time from 20 to 100 ns, as determined by applying Eq \ref{scaledEq1} for the local conditions of initial Rydberg gas density   This numerical approximation contains no provision for predissociation   Coupled rate-equation simulations for uniform volumes show that predissociation depresses yield to some degree, but has less effect on the avalanche kinetics \cite{Saquet2012}   Therefore, we can expect sets of numerically estimated shell densities, scaled to agree with the simulated ion density at the elapsed time of 100 ns to provide a reasonable account of the earlier NO$^+$ density profiles as a function of time    


\begin{figure}[h!]
\centering
\includegraphics[width=  4 \textwidth]{Shell_pop}
   \caption{Global population fractions of particles as they evolve in the avalanche of a shell-model ellipsoidal Rydberg gas with the initial principal quantum number and density distribution of Figure \ref{fig:shell}
   }
\label{fig:shell_yields}
\end{figure}

For each time step, the difference, $\rho_0 - \rho_e$ defines the neutral population of each shell   We assign a fraction of this population to surviving Rydberg molecules, such that the total population of NO$^*$ as a function of time agrees with the prediction of the shell-model simulation, as shown in Figure \ref{fig:shell_yields}   We consider the balance of this neutral population to reflect NO$^*$ molecules that have dissociated to form N($^4$S) $+$ O($^3$P)   Figure \ref{fig:shell} plots these surviving Rydberg densities as a function of radial distance for each evolution time   At the initial density of this simulation, note at each time step that a higher density of Rydberg molecules encloses the tail of the ion density distribution in $x$    

\subsection{Plasma expansion and NO$^+$ - NO$^*$ charge exchange as an avenue of quench}

We regard the ions as initially stationary   The release of electrons creates a radial electric potential gradient, which gives rise to a force, $-e\nabla \phi_{k,j}(t)$, that accelerates the ions in shell $j$ in direction $k$ according to \cite{Sadeghi 2012}:

\begin{align}
\frac{-e}{m'}\nabla \phi_{k,j}(t) = & \frac{\partial u_{k,j}(t)}{\partial t} \notag  \\
= & \frac{k_BT_e(t)}{m'\rho_j(t)} \frac{\rho_{j+1}(t) - \rho_j(t)}{r_{k,j+1}(t) - r_{k,j}(t)},
  \label{dr_dt}
\end{align}

\noindent where $\rho_j(t)$ represents the density of ions in shell $j$   

The instantaneous velocity, $u_{k,j}(t)$ determines the change in the radial coordinates of each shell, $r_{k,j}(t)$, 
\begin{equation}
\frac{\partial r_{k,j}(t)}{\partial t}=u_{k,j}(t) = \gamma_{k,j}(t) r_{k,j}(t),
  \label{dr_dt}
\end{equation}
\noindent which in turn determines shell volume and thus its density, $ \rho_j(t)$    
The electron temperature supplies the thermal energy that drives this ambipolar expansion   Ions accelerate and $T_e$ falls according to: 

\begin{equation}
\frac{3k_B}{2}\frac{\partial T_e(t)}{\partial t}= -\frac{m'}{\sum_{j}{N_j}}\sum_{k,j}{N_j u_{k,j}(t)\frac{\partial u_{k,j}(t)}{\partial t}},
  \label{dr_dt}
\end{equation}
\noindent where we define an effective ion mass, $m'$, that recognizes the redistribution of the electron expansion force over all the NO$^+$ charge centres by resonant ion-Rydberg charge exchange, which occurs with a very large cross section \cite{PPR}   
\begin{equation}
m' =\left (1+ \frac{\rho^*_{j}(t)}{ \rho_j(t)}\right) m ,
  \label{dr_dt}
\end{equation}
\noindent in which $\rho^*_{j}(t)$ represents the instantaneous Rydberg density in shell $j$ 

The initial avalanche in the high-density core of the ellipsoid leaves few Rydberg molecules, so this term has little initial effect   Rydberg molecules predominate in the lower-density wings   There, momentum sharing by charge exchange assumes a greater importance   

We see this most directly in the $\omega_2$ absorption spectrum of transitions to states in the $n_0 f(2)$ Rydberg series, detected as the long-lived signal that survives a flight time of 400 $\mu$s to reach the imaging detector   The balance between the rising density of ions and the falling density of Rydberg molecules depends on the initial density of electrons produced by prompt Penning ionization   As clear from Eq \ref{Eq:PenDens}, this Penning fraction depends sensitively on the principal quantum number, and for all principal quantum numbers, on the initial Rydberg gas density   

\begin{figure}[h!]
\centering
\includegraphics[width=  4 \textwidth]{w2_spectra}
   \caption{Double-resonant spectra of nitric oxide Rydberg states in the $nf$ series converging to NO$^+$ $v=0$, $N^+=2$ (designated, $nf(2)$), derived from the late-peak signal obtained after a flight time of 400 $\mu$s by scanning $\omega_2$ for $\omega_1$ tuned to NO A $^2\Sigma^+$ $v=0$, $N'=0$ for initial $nf(2)$ densities from top to bottom of 0 07, 0 10, 0 13, 0 19, 0 27, 0 30, 0 32 and $3 \times 10^{12}$ cm$^{3}$   
  }
\label{fig:w2_spectra}
\end{figure}

Figure \ref{fig:w2_spectra} shows a series of $\omega_2$ late-signal excitation spectra for a set of initial densities   Here, we see a clear consequence of the higher-order dependence of Penning fraction - and thus the NO$^+$ ion - NO$^*$ Rydberg molecule balance - on $n_0$, the $\omega_2$-selected Rydberg gas initial principal quantum number   This Penning-regulated NO$^+$ ion - NO$^*$ Rydberg molecule balance appears necessary as a critical factor in achieving the long ultracold plasma lifetime required to produce this signal   We are progressing in theoretical work that explains the stability apparently conferred by this balance   


\subsection{Bifurcation and arrested relaxation}

Ambipolar expansion quenches electron kinetic energy as the initially formed plasma expands   Core ions follow electrons into the wings of the Rydberg gas   There, recurring charge exchange between NO$^+$ ions and NO$^*$ Rydberg molecules redistributes the ambipolar force of the expanding electron gas, equalizing ion and Rydberg velocities   This momentum matching effectively channels electron energy through ion motion into the overall $\pm x$ motion of gas volumes in the laboratory   The internal kinetic energy of the plasma, which at this point is defined almost entirely by the ion-Rydberg relative motion, falls   Spatial correlation develops, and over a period of 500 ns, the system forms the plasma/high-Rydberg quasi-equilibrium dramatically evidenced by the SFI results in Figure \ref{fig:SFI}   

\begin{figure}[h!]
\centering
\includegraphics[width=  4 \textwidth]{Bifurcation pdf}
   \caption{$x,y$ detector images of ultracold plasma volumes produced by 2:1 aspect ratio ellipsoidal Rydberg gases with selected initial state, $40f(2)$ after a flight time of 402 $\mu$s over a distance of 575 mm   Lower frame displays the distribution in $x$ of the charge integrated in $y$ and $z$   Both images represent the unadjusted raw signal acquired in each case after 250 shots   
   }
\label{fig:bifurcation}
\end{figure}

In the wings, momentum redistribution owing to cycles of ion-Rydberg charge transfer retards radial expansion \cite{Pohl2003,PPR}   By redirecting electron energy from ambipolar acceleration to $\pm x$ plasma motion, NO$^+$ to NO$^*$ charge exchange dissipates electron thermal energy   This redistribution of energy released in the avalanche of the Rydberg gas to plasma, causes the ellipsoidal Rydberg gas to bifurcate \cite{Schulz-Weiling2016,Haenel2017}, forming very long-lived, separating charged-particle distributions   We capture the electron signal from these recoiling volumes on an imaging detector as pictured in Figure \ref{fig:bifurcation}   Here, momentum matching preserves density and enables ions and Rydberg molecules to relax to positions that minimize potential energy, building spatial correlation   

The semi-classical description of avalanche and relaxation outlined above forms an important point of reference from which to interpret our experimental observations   The laser crossed molecular beam illumination geometry creates a Rydberg gas with a distinctively shaped high-density spatial distribution   This initial condition has an evident effect on the evolution dynamics   We have developed semi-classical models that explicitly consider the coupled rate and hydrodynamic processes governing the evolution from Rydberg gas to plasma using a realistic, ellipsoidal representation of the ion/electron and Rydberg densities \cite{haenelCP}   No combination of initial conditions can produce a simulation that conforms classically with the state of arrested relaxation we observe experimentally  


\subsection{A molecular ultracold plasma state of arrested relaxation}

Thus, we find that spontaneous avalanche to plasma splits the core of an ellipsoidal Rydberg gas of nitric oxide  As ambipolar expansion quenches the electron temperature of this core plasma, long-range, resonant charge transfer from ballistic ions to frozen Rydberg molecules in the wings of the ellipsoid quenches the ion-Rydberg molecule relative velocity distribution  This sequence of steps gives rise to a remarkable mechanics of self-assembly, in which the kinetic energy of initially formed hot electrons and ions drives an observed separation of plasma volumes  These dynamics redistribute ion momentum, efficiently channeling electron energy into a reservoir of mass-transport  This starts a process that evidently anneals separating volumes to a state of cold, correlated ions, electrons and Rydberg molecules  

We have devised a three-dimensional spin model to describe this arrested state of the ultracold plasma in terms of two, three and four-level dipole-dipole energy transfer interactions (spin flip-flops), together with Ising interactions that arise from the concerted pairwise coupling of resonant pairs of dipoles \cite{SousMBL,SousNJP}   

The Hamiltonian includes the effects of onsite disorder owing to the broad spectrum of states populated in the ensemble and the unique electrostatic environment of every dipole   Extending ideas developed for simpler systems \cite{Burin1,Sondhi}, one can make a case for slow dynamics, including an arrest in the relaxation of NO Rydberg molecules to predissociating states of lower principal quantum number 

Systems of higher dimension ought to thermalize by energy transfer that spreads from rare but inevitable ergodic volumes (Griffiths regions) \cite{Sarang2, Roeck_griffith, RareRegions_rev, Thermal_inclusions}   However, a feature in the self-assembly of the molecular ultracold plasma may preclude destabilization by rare thermal domains:  Whenever the quenched plasma develops a delocalizing Griffiths region, the local predissociation of relaxing NO molecules promptly proceeds to deplete that region to a void of no consequence 

In summary, the classical dynamics of avalanche and bifurcation appear to create a quenched condition of low temperature and high disorder in which dipole-dipole interactions drive self-assembly to a localized state purified by the predissociation of thermal regions   We suggest that this state of the quenched ultracold plasma offers an experimental platform for studying quantum many-body physics of disordered systems  \\

\section{Acknowledgments}
This work was supported by the US Air Force Office of Scientific Research (Grant No  FA9550-17-1-0343), together with the Natural Sciences and Engineering research Council of Canada (NSERC), the Canada Foundation for Innovation (CFI) and the British Columbia Knowledge Development Fund (BCKDF)  





ground_truth: Symptoms of vitamin K deficiency include anemia, bruising, nosebleeds, bleeding of the gums, and heavy menstrual bleeding in women.