Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring peer support. We also consider the potential risks and benefits of self-disclosure and interacting with others on YouTube. To address these questions, we used qualitative inquiry informed by emerging techniques in online ethnography. We analyzed n = 3,044 comments posted to 19 videos uploaded by individuals who self-identified as having schizophrenia, schizoaffective disorder, or bipolar disorder. We found peer support across four themes: minimizing a sense of isolation and providing hope; finding support through peer exchange and reciprocity; sharing strategies for coping with day-to-day challenges of severe mental illness; and learning from shared experiences of medication use and seeking mental health care. These broad themes are consistent with accepted notions of peer support in severe mental illness as a voluntary process aimed at inclusion and mutual advancement through shared experience and developing a sense of community. Our data suggest that the lack of anonymity and associated risks of being identified as an individual with severe mental illness on YouTube seem to be overlooked by those who posted comments or uploaded videos. Whether or not this platform can provide benefits for a wider community of individuals with severe mental illness remains uncertain. How might the phenomenon of individuals with severe mental illness (SMI) such as schizophrenia, schizoaffective disorder, or bipolar disorder, who share their illness experiences through video narratives uploaded onto platforms like YouTube constitute the development of a naturally emerging peer support system? Or does this activity represent a risky process of self-exposure, and susceptibility to negative comments, unsolicited content, or exposure to harmful influences of others?YouTube is a video-sharing website created in 2005 that is currently the third most popular social media website worldwide after Facebook and Google+ Peer support in SMI includes a system of mutual giving and receiving where individuals who have faced and endured the adversity of mental illness can offer hope, companionship, and encouragement to others facing similar conditions Evidence suggests individuals with SMI are more likely to share personal views through blogging, build friendships on social media In the context of YouTube, groups of individuals with diverse health conditions, including multiple sclerosis First, to investigate this phenomenon of growing social media use among individuals with SMI, we provide a brief conceptual background to frame peer support and social media within the context of SMI. We then outline our process of exploring the comments associated with uploaded YouTube videos for expressions of peer support. Our analysis details how individuals with SMI use YouTube to interact with each other, and our discussion reflects the value of this popular social media website as a naturally occurring peer support platform.Peer support in psychiatry has its roots in the mental health consumer movement of the 1970s, where individuals living with SMI campaigned for basic human rights, mental health care reform, and the right to make their own health care choices Recent decades have seen the emergence and demonstrated effectiveness of formal peer provided services Informal peer support relationships are considered the foundation of peer support in mental health Social media websites have afforded new opportunities for individuals to connect with others, provide and receive support, and share their illness experiences Evidence suggests that individuals with SMI create online relationships at the same rate Social media may be well suited for peer support among individuals with SMI. These websites facilitate natural community building, where control of entry and exit are independent of social interaction, which allows users to avoid the anxiety and fears associated with face-to-face interactions To date, however, the benefits and understanding the why and motivation of online peer support in SMI have not been established. We know that disclosure of personal information through social media has been linked to individual behavioral control Recognizing the contribution of social media on health and help seeking behaviors among individuals with SMI we planned an investigation of YouTube. Specifically, we explore uploaded YouTube videos and associated comments for expressions of peer support. We conducted a qualitative analysis of comments detailing how individuals with SMI use YouTube as a platform indicative of naturally occurring peer support.Ethnographic methods in health research focus on expanding our understanding of illness experience and social practices in the context of culture within particular groups mental illness”, “schizophrenia”, “schizoaffective disorder” or “bipolar disorder”. To systematically identify a sample of relevant videos, we screened the first 100 videos for each search term. Relevant videos were defined as: posted by an individual, had no advertising, were in the first person, and included our search terms. Also, for each relevant video identified, YouTube generates a page list of 20 recommended videos that describe a similar topic based on our search history and the prior videos we selected and viewed. We reviewed the recommended video lists to identify additional relevant videos.In June 2013 we searched YouTube for publicly available videos that had been extensively viewed using the following search terms: “After viewing relevant videos, we further selected a smaller set of videos based on the following criteria: had a minimum of 5,000 views because videos with more views have more comments There has been considerable discussion surrounding the ethical concerns of analyzing data retrieved from social media The comments associated with the smaller set of identified videos were then exported as a pdf document into ATLAS.ti software Version 7.0 for thematic analysis. We applied an open coding approach, and developed codes based on the data as they naturally occurred Our search of YouTube yielded a combined total of approximately 746,200 videos. After screening 400 videos (100 per search term), we followed the recommended other video lists (YouTube) and evaluated 1,100 potential videos. We narrowed this set down to 63 by selecting only videos posted by an individual, without advertising, in the first person. We then applied our strict inclusion criteria and selected 19 videos and their associated 3,044 comments for analysis. The 44 excluded videos did not meet our criteria either because they did not have enough views, did not describe experiences of living with SMI, or appeared to be uploaded by private companies, documentary filmmakers, or academic institutions.The 19 videos were uploaded by 19 different individuals of which 8 self-identified as being diagnosed with bipolar disorder, 7 with schizoaffective disorder, and 4 with schizophrenia. Common topics included managing illness symptoms, challenges and benefits of seeking treatment, coping strategies for day-to-day concerns, efforts to reach out and help others with similar conditions, and personal stories about life goals, interests and future ambitions. The videos had an average of 19,786 views  and had been on YouTube between 87 and 1,798 days. Fifteen videos appeared to be posted by young adults (18–35 years) and four by middle-aged adults (36–55 years). We analyzed 3,044 comments posted to the videos, ranging from 27 to 592 for each video, of which 91% were posted by commenters and 9% were posted in response to commenters by video authors. On YouTube, users can rate comments as ‘inappropriate’, and when a comment receives sufficient ‘inappropriate’ ratings it is flagged. About 5% (n = 160) of the comments we analyzed were flagged for content viewed as inappropriate such as derogatory or discriminatory statements, advertisements, or spam.We determined four themes representing key aspects of peer support see . The theEfforts to reduce social isolation and achieve a sense of community were expressed in comments posted across all 19 videos. Comments showed appreciation for individuals who shared personal histories and lived experiences. Many commenters acknowledged that having a mental illness is a “lonely road” and were thankful for the videos, conveying reassurance to know that they are not alone with their illness. Individuals who said they felt that they could not talk to anyone about their illness because of fear, embarrassment or simply not having anyone close to them in their lives were particularly positive:Thank you soo much for this video it has made me feel a little less alone … i myself have bipolar 2 and have been off meds for about 6 months now and am also feeling the day to day fight i have in my head just to live in the real world …Comment on Video #5: video uploaded by female with bipolar disorderI can relate to almost everything you say … I’m too afraid to talk to people to have someone to relate to and discuss it with. So this video helps me in that I get to listen to your story and what you’re going through and feel like I’m not alone …Comment on Video #18: video uploaded by male with schizophreniaPeer support also allows individuals with SMI to relate to one another based on shared experiences and perceived membership in a wider supportive network. For some, this sense of belonging came from a sense of normalcy after watching the personal stories shared by others:I’m very happy i found you and your videos … Its so good to find people that make me think I’m more “normal” than i think. Thank you and hope alls good!Comment on Video #17: video uploaded by female with schizophreniaFor some, viewing the videos was a deeply emotional experience, generated by a sense of relief of finding someone to relate to:Literally, tears were streaming down my face as I watched this. Thank you so much … your descriptions were so spot on … it felt as if a female version of me from the future made this video … for no other reason but to give helpful advice.Comment on Video #17: video uploaded by female with schizophreniaThe YouTube videos also served as a source of inspiration, prompting individuals to do the same, and share their own illness stories. The importance of the Internet as a means for reaching others facing similar challenges was frequently cited:It’s okay, you’re not alone, there are many of our kind and we are lost without each other, but now thanks to the internet we can reach out to each other so we can discuss what we hear openly and honestly with no fear of being judged …Comment on Video #3: video uploaded by female with schizoaffective disorderI’m thinking about… making videos about my illness so I can connect with you and others here on youtube …Comment on Video #16: video uploaded by female with schizophreniaComments also reacted to the idea of sensing hope, expressed as optimism for overcoming challenges and moving forward with their lives:I can completely relate to your experience. I was diagnosed with Schizophrenia about two years ago and it has been hell for me. Your video was very inspiring to me and it gave me hope that things can get better.Comment on Video #16: video uploaded by female with schizophreniaComment on Video #6: video uploaded by female with schizoaffective disorder). Another suggested “Together us bipolar people will survive. It’s all about support. We will find a cure” .Comments also contained offers of comfort and encouragement. One commenter reassured “hang in there, things can and will get better … and thank you for sharing your story with us” !Comment on Video #2: video uploaded by female with schizoaffective disorderComment on Video #5: video uploaded by female with bipolar disorder).Extensive discussions emerged on how to cope with SMI. As individuals described their day-to-day challenges many reflected on the strategies that have helped them to cope and achieve a sense of “normalcy” in their everyday lives. Some commenters recommended coping strategies to each other, or asked for advice for dealing with their disorder. One viewer described how counseling serves as an important coping mechanism, “I go to counseling and that helps more than talking to anyone around me in my life because… the counselors at least have been around more bipolar people”  for the last 12 years. Several attempted suicides due to the fact that it took the “right” doctor to come into my path and finally diagnose me with Bipolar Disorder rather than your standard “Major Clinical Depression”Comment posted to Video #8: video uploaded by female with bipolar disorderComments highlighted individuals’ fear of visiting doctors because of the diagnosis that they might get or risk of being institutionalized. Individuals used YouTube to seek advice:i have conversations with my self and sometimes only notice what i have done when i stop talking… i also have violent urges out of the blue but i can control them at the moment. i know these are signs of schizerphrnia but im seeing my psychiatrist in 5 days an wondering if i should tell him … i dont want to be put in a mental ward will he put me in there if i tell him these things ???? please respond worriedComment on Video #1: video uploaded by female with schizoaffective disorderThe video author responded:he will DEFINITELY not be able to lock you up in psychiatric unit if you tell him what you’ve been experiencing. The only way they could send you to the hospital  is if you tell them that you’ve been hearing voices telling you to harm yourself or others, or if you have been having suicidal thoughts. … you should really tell your psychiatrist about this, though!!!Response to Comment on Video #1: video uploaded by female with schizoaffective disorder.Individuals with SMI appear to use YouTube to seek and share advice about medical related questions and concerns, which might or might not suggest they have been unable to find answers elsewhere. It is also possible that these individuals are looking to validate health information found elsewhere, such as from a recent medical visit or content from health-related websites, which led to their discovering personal accounts from others on YouTube. Whether these individuals feel most comfortable consulting with peers through YouTube, or perhaps use other social media platforms for the same purpose, remains unclear. Regardless, a rich dialogue surrounding shared experiences using medications and seeking mental health care emerged, illustrating another practical reason for engaging in these online peer-to-peer interactions through YouTube.The reciprocal exchange between YouTube commenters in response to content uploaded by individuals who self-identify as having a SMI including schizophrenia, schizoaffective disorder, or bipolar disorder, represents a dynamic, responsive, yet informal, system of peer support. Analysis of the data provided four themes consistent with the central role of peer support in SMI: minimizing a sense of isolation and providing hope; finding support through peer exchange and reciprocity; sharing strategies for coping with the day-to-day challenges of severe mental illness; and learning from shared experiences of medication use and seeking mental health care. We see peer support on YouTube as voluntary–an emergent phenomenon where users are unhindered and have individual autonomy to choose their level of disclosure and engagement, from viewing to commenting to uploading personal videos.Personal health information was frequently shared and rewarded by positive, encouraging, and insightful viewer responses. These interactions created, what appeared to be, a sense of belonging and means for coping with challenges of SMI. We observed that YouTube served as an environment where individuals with SMI could normalize one’s illness and assert their voice and identity by validating shared experiences with peers. That individuals were able to do this suggests the degree of safety they felt in contributing their videos and comments. This “peer exchange” was reinforced by strongly supportive, and at times combative, responses of participants in reaction to negative comments or “outsider” attempts to criticize uploaded videos.The observation of real world data without researcher interference was a methodological strength because it allowed us to document and analyze naturally occurring interactions. There were also limitations with our methods because we could not obtain data on individual motivation or intention to upload videos, post comments, or publicly disclose personal health information. This limitation with our data also restricted our ability for more in depth interpretation and analysis of the content posted to YouTube because of increased risk of bias. A previous study of YouTube found viewers were more comfortable commenting on lay videos, citing that the value of interacting with someone with firsthand experience meant it was someone who may be more likely to respond to questions or give advice Peer-to-peer interactions and open sharing of personal experiences living with SMI through YouTube exemplify how social media and the Internet are reshaping the way this marginalized group engages their environment and seeks and shares advice related to mental health care. As highlighted in prior research, by sharing illness experiences with others online and through social media, there is potential for improved health and psychosocial outcomes, including benefits such as learning from others, feeling supported, and forming relationships Then again, other studies found no clear health benefit of peer-to-peer interactions in social media As the benefits of social media for individuals with SMI remain unclear, how might sharing experiences and interacting with peers through YouTube specifically support mental health recovery? Listening to the experiences of other individuals with SMI offers value because authentic accounts are easier to understand, can make treatment information more relevant by putting it into a personal context, can help make sense of one’s situation, and can help with overcoming fears and feeling more confident in coping with symptoms Our findings reflect preliminary data that characterize naturally occurring interactions among individuals with SMI through social media and we acknowledge this new medium of communication poses potential risks. For instance, uncertainty remains about what level of information is necessary to determine what an online peer is saying is trustworthy and applicable Another concern might be that dramatic videos receive more attention through increased views and visibility while routine or unremarkable experiences may receive comparatively little notice At the time of this study, among the individuals who self-identified as having a SMI and who uploaded videos or posted comments to YouTube, we observed a sense of reward emerging from their interactions, mutual learning, and offered peer support. Of importance is our finding that peer support is happening naturally among individuals with highly stigmatized psychiatric illnesses within an unmonitored and public online platform. The lack of anonymity and associated risks of being identified as an individual with SMI seemed to be overlooked by commenters and video authors. Whether or not this platform can provide benefits for a wider group of individuals with SMI remains uncertain.


For individuals with HIV, heavy drinking can interfere with medication adherence and impair liver function. Yet, many individuals with HIV drink heavily. A recent alcohol intervention trial indicateThe sample consisted of 254 HIV-infected patients with past-month heavy drinking , participating in a randomized trial of brief alcohol interventions. ParticiThe intervention conditions evidenced few differences in motives at end-of-treatment , and no differences at end-of-study. However, baseline motives remained predictive of drinking at end-of-study .Although MI+HealthCall reduces drinking, it does not reduce drinking motives. Individuals participating in MI+HealthCall were more likely to transition to drinking due to social pressure, an indicator of lower-risk drinking. However


Although socially marginalized individuals with alcohol-use disorders (AUDs) experience severe alcohol-related harm, few enter treatment. ,2 DeveloParticipants  were socially marginalized individuals with AUDs participating in a larger study evaluating a new facility attendance and subsequent drinking outcomes. At baseline, study interventionists elicited participants' harm-reduction goals with an open-ended question (‘What would you like to see happen for you in the next 4 weeks?’) and provided participants with a list of 12 safer-drinking strategies . (3) Content analysis was used to categorize the goals and strategies participants endorsed.Mdn = 2.1, IQR = 2) and one strategy . The 5 most highly endorsed goals categories included drug and alcohol-related goals , basic-need goals , health-related goals , and quality-of-life goals . Changing manners of drinking  was the most highly endorsed strategy type, followed by buffering the effects of alcohol on the body  and reducing drinking.Seventy-six participants (97.4%) generated and endorsed at least one goal (Most participants did generate and endorse harm-reduction goals and safer-drinking strategies, which replicated US findings ,5. These


Drinking in youth is linked to other risky behaviours, educational failure and premature death. Prior research has examined drinking in mid and late teenagers, but little is known about the factors that influence drinking at the beginning of adolescence. Objectives were: 1. to assess associations of parental and friends’ drinking with reported drinking among 11 year olds; 2. to investigate the roles of perceptions of harm, expectancies towards alcohol, parental supervision and family relationships on reported drinking among 11 year olds.Analysis of data from the UK Millennium Cohort Study on 10498 11-year-olds. The outcome measure was having drank an alcoholic drink, self-reported by cohort members.13.6 % of 11 year olds reported having drank. Estimates reported are odds ratios and 95 % confidence intervals. Cohort members whose mothers drank were more likely to drink . Cohort members whose fathers drank were also more likely to drink but these estimates lost statistical significance when covariates were adjusted for . Having friends who drank was strongly associated with cohort member drinking . Associated with reduced odds of cohort member drinking were: heightened perception of harm from 1–2 drinks daily ; and negative expectancies towards alcohol . Associated with increased odds of cohort member drinking were: positive expectancies towards alcohol ; not being supervised on weekends and weekdays ; frequent battles of will ; and not being happy with family .Examining drinking at this point in the lifecourse has potentially important public health implications as around one in seven 11 year olds have drank, although the vast majority are yet to explore alcohol. Findings support interventions working at multiple levels that incorporate family and peer factors to help shape choices around risky behaviours including drinking. Regular heavy and binge drinking are recognised as major public health problems in terms of mortality, morbidity and wider social and economic consequences , 2, and Adolescence is a time of dramatic change that influences young people’s sense of autonomy and their exploration of risky behaviours. Factors shown to influence young people’s drinking include parent and peer drinking behaviours, perceptions of risk, expectancies towards alcohol and supportive family relationships –17. MostGiven the paucity of work on the initiation of drinking in very early adolescence, in this paper we address two research objectives 1. to assess associations of parental and friends’ drinking with reported drinking among 11 year olds; and 2. to investigate the roles of perceptions of harm, expectancies towards alcohol, parental supervision and family relationships on drinking among 11 year olds. To do this we analysed data from the large contemporary population based Millennium Cohort Study.The Millennium Cohort Study (MCS) is a UK nationally representative prospective cohort study of children born into 19244 families between September 2000 and January 2002 . ParticiIn a question developed for the MCS survey, cohort members were asked “Have you ever had an alcoholic drink? That is more than a few sips?” (yes/no).Parents were asked about the frequency and amount of alcohol they drank. “How often do you have a drink that contains alcohol?” . “How many standard alcoholic drinks do you have on a typical occasion?” Response options on frequency and quantity of alcohol consumed meant it was only possible to approximate drinking categories as set out in guidelines by the UK Department of Health. The same categories were used for mothers and fathers as follows: None; Light/moderate - those who drank but were not heavy/binge drinkers; Heavy/binge - 4 or more times a week and drinks a minimum of 3–4 drinks per drinking occasion, or a minimum of 5–6 drinks per occasion. Separate categories were created for cohort members where information on parents’ drinking behaviour was missing and when the father was absent from the household.Friends’ drinking was assessed by asking cohort members “How many of your friends drink alcohol?” Response categories were recoded: None of them as No; Some/Most/All of them as Yes; don’t know was retained as a separate category.Gender; puberty, assessed from responses by the mother to questions ; birth order (first vs subsequent); current socioemotional difficulties  ; antisocPerception of risk due to alcohol was assessed by the question “How much do you think people risk harming themselves if they drink one or two alcoholic drinks nearly every day?” . Positive expectancies towards alcohol were assessed by the following questions: “Drinking beer, wine, or spirits is a way to make friends with other people”; “It is easier to open up and talk about one's feelings after a few drinks of alcohol”; “Drinking alcohol makes people …worry less; …happier with themselves”. Negative expectancies were assessed using questions: “Drinking alcohol … gets in the way of school work; … makes it hard to get along with friends”; “If I drank alcohol without my parents’ permission I would be caught and punished”. Items were summed and used as two separate scales .Parental supervision was assessed by questions about the weekday and weekend frequency of cohort member spending unsupervised time with friends . Items were combined into a three category variable: rarely/never , sometimes, often (unsupervised most weekends and at least one day per week).Markers of family relationships were: frequent battles of will with cohort member (yes/no); mother-cohort member closeness (extremely/very close vs fairly/not very close); cohort member happiness with their family  .Data on cohort member drinking were available for 12644 participants. Missing data reduced the sample to 10498 (83.0 %), as follows: friends drinking = 56; puberty = 1010; socioemotional difficulties = 475; religious affiliation = 34; antisocial behaviours = 27; perception of harm = 337; positive expectancies = 189; negative expectancies = 315; parental supervision = 87; frequent battles = 1106; relationship between mother and child = 762; happy with family = 91.To estimate the association between our exposures of primary interest – mother’s, father’s or friends’ drinking with cohort member drinking, we ran three sets of logistic regression models adding covariates in stages. Boys were more likely to report drinking compared with girls (15.7 vs. 11.3 %), but as there were no gender differences in observed associations between parent and friends’ drinking with cohort member drinking, we present analyses for boys and girls combined, and all models adjust for gender.Model 0 is the baseline model which includes the primary independent variable  and gender.Model 1 additionally adjusts for control variables: puberty, birth order, socioemotional difficulties, antisocial behaviours, truancy, smoking, income, religion and for other alcohol exposure variables e.g. when mother’s drinking is the primary exposure, we add father’s and friends’ drinking to this step of the analysis.Model 2 is fully adjusted adding in potential moderator and mediator variables, perception of harm due to alcohol, positive and negative expectancies, parental supervision and family relationships .All analysis was carried out using Stata version 13.1 (Stata Corp).p < 0.001), to have started puberty (14.3 % vs 13.2 %), to be a second or later born child (14.0 % vs 12.9 %), to have socioemotional difficulties , to report antisocial behaviours , report truancy , smoke cigarettes , to be from poorer families  and not have any religious affiliation . Table Overall 13.6 % of cohort members reported having drunk more than a few sips of an alcoholic drink. Cohort members who reported drinking were more likely to be boys . Cohort members for whom data on mother’s drinking was missing were also more likely to drink . Cohort members whose fathers drank were also more likely to drink but these estimates lost statistical significance when covariates were taken into account . Having friends who drank was associated with more 7 times the odds of cohort member drinking, and twice the odds when cohort members reported not knowing whether their friends drank. These estimates changed on adjustment for covariates but remained highly statistically significant  (Table Perceptions of harm, expectancies towards alcohol, parental supervision, and family relationships were associated with the likelihood of cohort member drinking in the expected direction  Table 3.Our results suggest that nearly 14 % of 11 year olds in the UK have had an alcoholic drink. The odds of drinking were greater when their friends drank compared to when their parents drank: boys and girls who reported having friends who drank were five times more likely to report drinking themselves compared to those who reported having friends who did not drink. Having a mother who drank heavily was associated with an 80 % increased odds of drinking, however, fathers’ drinking was not independently associated with children’s drinking. Our results suggest that 11 year olds’ perceptions of risk, their expectancies towards alcohol and relationships with their families were independently related to the likelihood of drinking.Distinct strengths of this work are that we used data from a large sample representative of 11 year olds in the UK; we simultaneously examined relationships with parents and friends drinking; and we were able to take into account rich contextual information about young people’s understanding of the risk of drinking alcohol, their expectancies, positive and negative, towards alcohol and family relationships. On the other hand, there are several limitations to acknowledge, including that the analyses were cross sectional as information on cohort member and friends' drinking, perceptions of harm and expectancies around drinking are only available from one wave of data collection thus causal inference cannot be drawn; the data on cohort member and friends’ drinking were developed for the MCS survey making it difficult to compare prevalence rates with other studies, although closed questions as used in this study have been shown to be valid markers of alcohol consumption in adolescents ; the datPrior work has charted the prevalence of drinking among 11 year olds in the UK  and elseA recent Cochrane review  concludeOur study was not able to examine contexts around drinking occasions among 11 year olds – who do they drink with? Where, when and what do they drink? How do they acquire alcohol and what are the broader social norms around drinking? One study that compared young people’s drinking in Italy and Finland showed that Italian youth were more likely to drink with meals under family supervision, whereas Finnish youth were more likely to drink in settings that led to drunkenness . Being aExamining drinking at this point in the lifecourse has potentially important public health implications as around one in seven 11 year olds have drank, although the vast majority are yet to explore alcohol. Even though the links between early drinking and later life drinking problems remain unclear, we need to further improve our understanding of the relative importance and meaning of drinking in early adolescence as regular and heavy drinking among young people is linked to harmful behaviours and premature death. However, apparent culturally specific differences in the meaning of drinking underscores the importance of identifying factors that shape early drinking experiences across settings. Improving our understanding of context specific drivers of early drinking presents golden opportunities to develop effective policy and prevention strategies.Ethical approval was not required for secondary analysis of publically available archived data.


For centuries, the thymus has been an organ in search of a function. The fact that it is a large mass of tissue in infancy was not appreciated at the beginning of the twentieth Century, as autopsies performed in infants succumbing to fatal illnesses such as diphtheria, revealed a small thymus. This resulted from stress during the illness, but the small size of the thymus was thought to be the norm. When infant death occurred during anesthesia for stress-unrelated conditions, fatality was blamed not on the anesthetic but on the large thymus. Some doctors even prescribed radiation therapy to shrink the thymus , not reaPrior to 1961, the thymus was considered not to have any role in immunity. The major reasons for this can be summed up as follows. Unlike lymphocytes obtained by thoracic duct cannulation or from spleen and lymph nodes, thymus lymphocytes were generally poor in their ability to initiate immune reactions after adoptive transfer to appropriate recipients. Thoracic duct lymphocytes could home from blood into lymphoid tissues, “the only exception” being “the thymus in which very few small lymphocytes” appeared “to lodge” . The proIn the late 1950s, I was working on mice with lymphocytic leukemia that was induced in low-leukemic strain mice [as demonstrated by Ludwik Gross ] by injeThe survivors grew well at first but, after weaning, many wasted and died prematurely whether inoculated with virus or not. Adult thymectomy, on the other hand, had never shown any untoward effects such as weight loss or obvious pathology. This led me to conclude “that the thymus at birth may be essential to life” . HistoloThe few neonatally thymectomized mice that did eventually reject allogeneic skin grafts were later grafted again with skin from the same donors but showed no evidence of a second set response . By contSalmonella typhi H antigen and found this to be impaired (I tested the ability of my neonatally thymectomized mice to produce antibody to impaired .Grafting thymus tissue to neonatally thymectomized mice prevented immunological deficiency. Although implantation of syngeneic thymus tissue allowed these mice to develop a normal immune system, grafting a thymus derived from a foreign strain induced specific immune tolerance to the histocompatibility antigens of the donor. Thus, lymphocytes developing in the thymus in the presence of foreign cells must have been deleted . Hence,Showing that cells from the thymus migrated into the lymphoid tissues was difficult at that time, since no markers had been found to identify cells from different locations. So I made use of the T6 mouse strain the cells of which could easily be identified at metaphase by the presence of 2 min chromosomes. Neonatally thymectomized F1 hybrid mice in which one parent was T6, were grafted with thymus from the other parental strain and immunized with skin from various donors. An analysis of the chromosome constitution of the cells in metaphase in the spleen showed that 15–20% had originated from the thymus graft .My conclusions concerning the immunological function of the thymus were regarded with skepticism by the immunological community. For example, Medawar was not convinced as evident from a letter he sent to me in which he wrote: “I take it that the thymic tissue seen in fishes is wholly or predominantly epithelial, as its phylogenetic origin suggests. It is a matter of some interest that many organs, which seem to become redundant in the course of evolution undergo a sort of lymphocytic transformation” . TrivialThese criticisms did not last very long as I and several other researchers repeated, confirmed, and extended my results. It was evident, for example, that the adult thymus would still play a role in immunogenesis and this was shown when the rest of the lymphoid system was destroyed by total body irradiation and the mouse protected by an injection of bone marrow , 17. TheThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Owing to the growth of high performance network technologies, multimedia applications over the Internet are increasing exponentially. Applications like video conferencing, video-on-demand, and pay-per-view depend upon encryption algorithms for providing confidentiality. Video communication is characterized by distinct features such as large volume, high redundancy between adjacent frames, video codec compliance, syntax compliance, and application specific requirements. Naive approaches for video encryption encrypt the entire video stream with conventional text based cryptographic algorithms. Although naive approaches are the most secure for video encryption, the computational cost associated with them is very high. This research work aims at enhancing the speed of naive approaches through chaos based S-box design. Chaotic equations are popularly known for randomness, extreme sensitivity to initial conditions, and ergodicity. The proposed methodology employs two-dimensional discrete Henon map for (i) generation of dynamic and key-dependent S-box that could be integrated with symmetric algorithms like Blowfish and Data Encryption Standard (DES) and (ii) generation of one-time keys for simple substitution ciphers. The proposed design is tested for randomness, nonlinearity, avalanche effect, bit independence criterion, and key sensitivity. Experimental results confirm that chaos based S-box design and key generation significantly reduce the computational cost of video encryption with no compromise in security. The advancements in networks and communication have promoted the usage of digital multimedia data in the field of education, commerce, defense, and entertainment. Usage of video applications such as video messaging, video conferencing, video surveillance, and Internet video sites such as YouTube is becoming increasingly popular and pervasive. Telemedicine is an application of clinical medicine and information technology where consultation, medical procedures, and examinations are performed remotely using interactive audiovisual media. These applications generate and transmit large amount of sensitive data in a resource constrained environment characterized by lower bandwidth, frequent packet drops, quality of service concerns, and limited computational resources of the communicating devices. The increasing use of video based applications demands not only secure algorithms for transmission and storage of videos but also efficient algorithms to reduce computational overhead.Confidentiality for multimedia data is offered by means of encryption, in which the legitimate users can only gain access to data with the secret keys possessed by them. Video encryption algorithms are classified based on the way of encrypting data. Fully Layered Encryption (Naive Encryption) considers the whole content of video stream as a sequence of bits and encrypts with text based symmetric 3 algorithms such as Advanced Encryption Standard (AES), Blowfish, and Triple DES and so forth , 2. As tTo increase the encryption efficiency, a large number of permutation and selective video encryption strategies are proposed in the literature. Permutation based video encryption algorithms scramble the bytes within every frame of a video stream. In Zig-Zag permutation , an indiSelective encryption algorithms encrypt only selective subset of bytes within video frames to reduce the volume of data to be encrypted and at the same time to preserve a sufficient level of security. Meyer and Gadegast  proposedFrom the literature, it can be inferred that there is no scheme that fits all applications. Permutation and selective encryption algorithms can reduce the computational overhead, but for complete and provable security of video in sensitive applications such as telemedicine, military, and business meetings, the entire video stream needs to be encrypted. Hence, development of video encryption algorithms encrypting the entire video stream at low computational cost is inevitable.The proposed system encrypts the entire stream of video data but with a significant reduction in computational time through the application of Henon map. Henon map is employed in video encryption to address two levels of security: (i) ensemble of dynamic and key-dependent S-box with symmetric algorithms (Blowfish and DES) and (ii) generation of one-time keys for simple substitution ciphers.n” bit word, but the output can be an “m” bit word, where “m” and “n” are not necessarily the same. An S-box can also be keyed or keyless and linear or nonlinear. S-boxes help the block ciphers to exhibit two important characteristics, namely, diffusion and confusion. The idea of diffusion is to hide the relationship between the plain text and the cipher text, which will frustrate the adversary who uses cipher text statistics to find the plain text. The idea of confusion is to hide the relationship between the cipher text and the key, which will frustrate the adversary who uses cipher text to find the key.In cryptography, an S-box is a basic component of symmetric key algorithms, which performs substitution. It is typically used to establish a nonlinear relationship between the key and the cipher text. An S-box should exhibit cryptographic properties such as bijection, strict avalanche, output bits independence, and equiprobable input/output XOR distribution. The input to an S-box could be an “Random: pseudorandom numbers are used to generate the entries in the S-boxes.Random with testing: the S-box entries are chosen randomly and tested against various criteria and the values that do not pass are not considered.Human-made: the S-boxes of DES are designed in this mode, where the entries are filled manually. However, the approach is difficult to carry out for large S-boxes.Math-made: S-boxes are generated by using mathematical principles, and hence they have proven security against linear and differential cryptanalysis. Use of chaotic equations is one such mathematical way of S-box design.Eight S-boxes are used in DES, in which each S-box is constructed as a table of four rows and sixteen columns . The desDiscretized chaotic maps are used for generating dynamic and cryptographically strong S-boxes by Tang and Liao . The cryHenon map has been used for pseudorandom number generation  and for xn,  yn) in the plane and maps it onto a new point  as defined by the equationsα” can be in the range of 1.16 to 1.41. “β” can be in the range of 0.2 to 0.3. “x0” can be in the range of −1 to 1. “y0” can be in the range of −0.35 to 0.35. Skip value can be in the range of 80 to 1000.The random-like, unpredictable dynamics and simplicity in realization of chaotic systems make them suitable for cryptographic applications. The Henon map is a two-dimensional discrete dynamical system introduced by Michael Henon as a simplified model of Lorenz system . Henon mα = 1.4 and β = 0.3, as shown in Henon map is found to exhibit good chaotic behavior for values A minute variation in the initial parameters even in ten-millionth place value of the chaotic systems could yield widely divergent results. In any cryptographic application, the property of confusion aims to make the relationship between statistics of cipher and key as complex as possible to thwart attempts to discover the key. The property of diffusion aims to make the statistical relationship between the input and cipher as complex as possible. The extreme sensitiveness to initial conditions of the Henon map makes it suitable for cryptographic applications due to the enhanced confusion and diffusion properties.Certain applications such as business and military meetings require a very high level of security. Extreme level of security could be achieved only by naive approaches of video encryption but with high computational costs. In order to increase the encryption speed and to reduce the computational cost of symmetric algorithms, the proposed S-box design using Henon maps can be integrated into the chosen symmetric algorithms.The various steps involved in integration of the proposed S-box design with symmetric algorithms including Blowfish and DES are as follows.α,  β and seed values x0,  y0.The parameters of the Henon map  The number for decimal places of the mantissa that are to be supported by the calculating machine.The number of iterations after which the first value is to be picked for generating keys.The skip value to be maintained for picking successive values thereafter.For generation of S-boxes, the following parameters are to be exchanged using the public keys of the communicating entities or through a secret channel. x and y of length d = wm/2. The number of iterations (Nc) is given by w” represents the word length of S-box elements. “m” represents the total number of S-box elements. “v” represents the skip value to be maintained for picking up successive values in iterations of Henon map equations.(1) Iterate the two-dimensional equations of the Henon map for a predefined number of times, which is specific to the crypto algorithm chosen for encryption. Process the result in two one-dimensional arraysx and y into subarrays of length equal to the word length (w) of the S-box elements.(2) Split the arrays (3) Mix the individual subarrays with each other at predefined crossover points as illustrated in τx′ and τy′) of each individual array of x′ and y′.(4) Calculate the medians  To generate a binary sequence, compare each element of (6) Partition each binary sequence across the word length and use alternatively to generate the individual S-box elements.A sample 8-bit S-box with eight rows and eight columns (64 elements) is illustrated in . It coulV be the video to be encrypted consisting of frames F1, F2, F3,…, Fz. The S-boxes generated are integrated with the Feistel cipher structure of both Blowfish and DES to perform encryption. The entire video stream is treated as a sequence of bits and is completely encrypted with the corresponding crypto algorithm. A detailed description of Blowfish and DES can be found in [Let found in  and 12]V be the Integration of the proposed S-box design with DES aims to enhance security through dynamic and key-dependent S-boxes. Existing S-box design of DES is static and hence it is possible for an opponent to perform cryptanalysis by exploiting its weaknesses . CryptanExisting Blowfish algorithm requires 521 encryptions for generation of P-arrays and S-boxes. The proposed S-box design when integrated with Blowfish results in significant reduction of time by eliminating the 521 encryptions. Thus, the proposed S-box design makes Blowfish suitable for memory limited and low powered devices with no compromise in security.Nonlinearity is the major requirement of any S-box design. The proposed design of S-boxes is tested for nonlinearity against different criteria  as givenThe relation between the input and output bits is plotted in For the given inputs  and , which differ by one bit, the corresponding outputs are  and  which differ by at least two bits.For the given inputs  and , which differ by two middle bits exactly, the corresponding outputs are  and  which differ by at least two bits.For the given inputs  and , which differ in two middle bits exactly, the corresponding outputs are  and  which differ by at least two bits.The proposed S-box design has been tested for the above four criteria for 30 test cases drawn from 10 samples of S-boxes. About 99% of the test cases were found satisfactory with respect to all criteria.For a good cryptosystem, the output should vary significantly by a larger number of bits for minor changes in input. A sample of generated and encoded values in decimal format for minor changes in seed values of Henon map is shown in k1, k2 ∈ K should be completely different. The proposed methodology has been examined with Blowfish encryption for text inputs with a difference of 1 bit retaining all the other inputs to be similar. If a function is to satisfy the strict avalanche criterion, then each of its output bits should change with a probability of one half whenever a single input bit is complemented. The deviation has been analysed in each round of Blowfish encryption for the input parameters, Key = 0 × 78906543,   X0 = 0.26, Y0 = 0.29, skip value = 100 and slightly differing plain text input 1 = 0 × 1234876509874563, and plain text input 2 = 0 × 1234876509874562. It can be observed from A desirable property of any cryptographic algorithm is that the key space should be discretized in such a way that two ciphers encrypted by two slightly different keys Certain applications like pay TV require medium level of security but high speed for video encryption. To facilitate this, the chaotic values generated by the Henon map are encoded as one-time keys. As the encryption and decryption involve a simple and reversible XOR operation of keys with all the pixels of every frame, the time taken for encryption and decryption is significantly reduced.The steps involved in generation of random keys for simple substitution cipher operating in counter mode of operation are as follows.P1,   P2, P3,   P4) as mentioned in P5) is also exchanged. For random generation of keys, the seed values X0 and Y0 are incremented by the value of P5 during encryption of every frame.In addition to the exchange of secret parameters (Nk) is given by z” represents the number of frames in the video sequence. “l” represents the number of pixels in every frame. “b” represents the number of bits used for pixel representation. “v” represents the skip value to be maintained for picking up successive values in iterations of Henon map equations.(1) Iterate the Henon map for a predefined number of times, which directly depends upon number of frames and count of pixels in each frame. The number of iterations  Create a key table consisting of all possible 2(3) Encode the chaotic values generated to the indices of the key table using the same procedure as described in V be the video to be encrypted consisting of frames F1, F2, F3,…, Fz. The number of pixels in every frame is represented by “l” and “b” bits are used for every pixel representation.(1)R1, R2,…, Rl) of the frame (F1) with the keys  in keyset (S1) to produce the ciphered frame (C1) as illustrated in Perform XOR operation on every pixel ((2)P1) using the increment parameter (P5) to generate new random keys for encryption of every frame, thereby making the crypto system as strong as one-time pads. To enhance the speed of encryption, the key generation can be done as a preprocessing step prior to encryption.Update the seed  Correlation Coefficient. A high level of correlation exists among pixels in adjacent frames of a video and in order to make a video encryption algorithm resistant towards crypt analysis, the correlation between the adjacent frames of the ciphered video must be minimized. The correlation coefficient (ρ) is calculated byp and q are the intensity values of two pixels in the same position of adjacent frames and G represents the total number of pixels in a frame. From (B) Histogram Analysis. Statistical attacks are made by exploiting the predictable relationships between the plain and cipher frame pairs. Significant changes in the histograms of original and cipher frames reveal the strength of the algorithm against statistical attacks. The histograms of red, green, and blue components of original and ciphered frames are illustrated in Figures The National Institute of Standards and Technology (NIST) has recommended certain set of statistical tests for detecting deviations of a binary sequence from randomness . The ranThe performance metrics for video encryption such as visual degradation, trade-off between encryption ratio and speed, compression friendliness, and format compliance are examined in both applications of Henon maps, namely, (i) integration of proposed S-box design with DES and Blowfishand (ii) generation of random keys for simple substitution cipher in counter mode of operation.Visual degradation measures the perceptual distortion of the video data with respect to the plain video. It can be inferred from Figures Encryption ratio measures the ratio between the size of the encrypted part and the whole data size. In order to increase the speed of the encryption algorithm, encryption ratio has to be minimized. A balance between security and speed is achieved by completely encrypting the entire data and at the same time increasing the speed of encryption through modified design of S-boxes. The proposed design significantly reduces the time taken for encryption/decryption by eliminating the 521 iterations of Blowfish making it suitable for real time processing. In application of the proposed design for generation of random key, the encryption is carried out in counter mode which involves parallel processing of multiple frames for significant reduction in encryption/decryption time. Since every frame is operated independently of the other frame, propagation of bit errors in transmission is completely eliminated and hence the quality of decrypted video is ensured.The proposed video encryption algorithm is compression friendly as it has no impact on the efficiency of data compression. Also the size of the data is not increased with reference to the original size of the file.The syntax of the encrypted video stream of the proposed video encryption algorithm is also compliant with the standardized syntax of the compressed video stream. The encryption does not disturb the standardized syntax structure of the video stream such as the frame header, slice header, and the block header.This research work deploys the concept of Henon map to create dynamic S-boxes for symmetric key cryptosystems and for generation of random keys for simple substitution ciphers. The randomness, sensitivity to initial conditions, and ergodicity make Henon map suitable for S-box generation and one-time pads. The ease of encoding and transformation technique makes the system suitable for memory limited and low powered devices. The proposed methodology attains a high level of security at a less computational time. Experimental results prove the robustness of the algorithm against statistical attacks, key sensitivity tests, and randomness test and in performance enhancement. Future work may be attempted at deriving mathematical proofs for nonlinearity. The proposed video encryption algorithm may be extended and tested for mobile and cloud environments.


Paramedic trainees in developing countries face complex and chaotic clinical environments that demand effective leadership, communication, and teamwork. Providers must rely on non-technical skills (NTS) to manage bystanders and attendees, collaborate with other emergency professionals, and safely and appropriately treat patients. The authors designed a NTS curriculum for paramedic trainees focused on adaptive leadership, teamwork, and communication skills critical to the Indian prehospital environment.Forty paramedic trainees in the first academic year of the 2-year Advanced Post-Graduate Degree in Emergency Care  program at the GVK-Emergency Management and Research Institute campus in Hyderabad, India, participated in the 6-day leadership course. Trainees completed self-assessments and delivered two brief video-recorded presentations before and after completion of the curriculum.p < 0.01) and body language of paramedic trainees . Self-reported competency surveys indicated significant increases in leadership , public speaking , self-reflection , and self-confidence .Independent blinded observers scored the pre- and post-intervention presentations delivered by 10 randomly selected paramedic trainees. The third-party judges reported significant improvement in both confidence (25 %, Participants in a 1-week leadership curriculum for prehospital providers demonstrated significant improvement in self-reported NTS commonly required of paramedics in the field. The authors recommend integrating focused NTS development curriculum into Indian paramedic education and further evaluation of the long term impacts of this adaptive leadership training. Paramedic trainees in developing countries often face complex and chaotic clinical environments that demand effective leadership, communication, and teamwork. Providers must rely on such non-technical skills (NTS) to manage dozens of bystanders and attendees, collaborate with other emergency professionals, and safely and appropriately treat patients –5. The AUntil recently, India lacked a centralized system for prehospital emergency medical care analogous to the 9-1-1 system utilized in the USA. In August 2005, the GVK-Emergency Management and Research Institute (GVK-EMRI), a non-profit organization based in the state of Andhra Pradesh, India, launched the first government-sponsored ambulance service under a single call number (1-0-8). The system has since grown to serve 15 Indian states and 2 union territories with a fleet of over 10,000 ambulances [Our previous work identified several elements of clinical practice that Indian paramedic trainees found challenging   . Crowd cn = 20, median age = 30 years) and Chhattisgarh . Three students who participated in the curriculum were not present for either the pre- or post-intervention survey and were excluded from the analysis.Forty paramedic trainees in the first academic year of the 2-year Advanced Post-Graduate Degree in Emergency Care  program at the GVK-EMRI campus in Hyderabad, India, participated in the 6-day leadership curriculum. Of the 40 paramedic trainees, 28 were male and 12 were female. The trainees varied in age from 24 to 48 years and primarily hailed from the Indian states of Gujarat . Judges were provided a nominal compensation of $0.05 per 30-s clip as per the Mechanical Turk platform guidelines. Judges rated and scored the presentations on overall quality, body language , emotional engagement , content , auditory delivery , confidence, and English language competency. Judges were blinded as to whether the video clip was pre- or post-intervention. The study was exempted from institutional review by Stanford University IRB.Students reported any self-perceived changes in their skills following participation in the 6-day curriculum on two surveys that used Likert-style scales. On the first survey, trainees rated their agreement with statements describing improvements in communication and English language comprehension and literacy .Assessment scores were compared using pair-wise Student’s p < 0.01) and body language of paramedic trainees .Independent blinded observers scored 10 randomly selected pre- and post-intervention presentations delivered by Indian paramedic trainees , public speaking , self-reflection , and self-confidence .When comparing pre- and post-curriculum self-reported competencies Table , paired n = 37) completed a survey at the conclusion of their leadership training . However, to reduce rater bias and increase reliability, we had 30 different judges rate each video clip on the 5-item Likert scale. Due to the short duration of the course, our primary outcome measures focused on public speaking because other NTS domains, like leadership and teamwork, take time, experience, and reflection to develop. We plan to utilize the video-based assessment tool in the future to assess multiple NTS, to extend the duration of follow-up, and to assess a larger cohort of paramedic trainees. Finally, to reduce the inherent bias in repeated testing of a skill, we randomized the order and subject of presentation of students.Our study was primarily limited by sample size of the assessment cohort, the duration of the curriculum, the short-term follow-up, and the complex nature of NTS development. Although we had strong anecdotal evidence of improvement, we aimed to pilot a video-based third-party assessment. Anonymous, blinded judges evaluated pre- and post-intervention oral presentations of 10 randomly selected students on a 7-item instrument Fig. . The vidShort-term outcomes of this leadership curriculum demonstrate a significant increase in paramedic trainees’ self-perceived confidence, communication, and leadership skills. Blinded third-party observers corroborated the improvement in confidence and body language of a subset of trainees. Our video-based assessment pilot demonstrated the feasibility of cost-effective, blinded evaluation of NTS skills using standardized tasks. We recommend integrating focused NTS development curriculum into Indian paramedic education and further evaluation of the long-term impacts of this adaptive leadership training.


Current technologies to allow continuous monitoring of vital signs in pre-term infants in the hospital require adhesive electrodes or sensors to be in direct contact with the patient. These can cause stress, pain, and also damage the fragile skin of the infants. It has been established previously that the colour and volume changes in superficial blood vessels during the cardiac cycle can be measured using a digital video camera and ambient light, making it possible to obtain estimates of heart rate or breathing rate. Most of the papers in the literature on non-contact vital sign monitoring report results on adult healthy human volunteers in controlled environments for short periods of time. The authors' current clinical study involves the continuous monitoring of pre-term infants, for at least four consecutive days each, in the high-dependency care area of the Neonatal Intensive Care Unit (NICU) at the John Radcliffe Hospital in Oxford. The authors have further developed their video-based, non-contact monitoring methods to obtain continuous estimates of heart rate, respiratory rate and oxygen saturation for infants nursed in incubators. In this Letter, it is shown that continuous estimates of these three parameters can be computed with an accuracy which is clinically useful. During stable sections with minimal infant motion, the mean absolute error between the camera-derived estimates of heart rate and the reference value derived from the ECG is similar to the mean absolute error between the ECG-derived value and the heart rate value from a pulse oximeter. Continuous non-contact vital sign monitoring in the NICU using ambient light is feasible, and the authors have shown that clinically important events such as a bradycardia accompanied by a major desaturation can be identified with their algorithms for processing the video signal. FurtherCamera-based non-contact estimation of heart rate in the NICU using standard video cameras was first reported in 2012 [A team of academic researchers working with Philips  have since made video camera recordings of 19 infants in two NICUs in California and the Netherlands . The camAnother group of researchers have recently reported spot measurements of heart rate using a Sony camera, and of respiratory rate using an infra-red thermal camera . Both thet al. [In 2011, Abbas et al.  describeet al. .The use of standard cameras and thermal imaging is further explored in . A camerpSO2) derived from an analysis of the reflectance signals acquired with a digital video camera in a real hospital environment, with regular ambient light and without affecting patient care.It is important for the management of infants in the NICU that vital sign measurement is continuous. In this Letter, we show how the cardiorespiratory status of an infant can be tracked from continuous measurements of heart rate, respiratory rate and peripheral oxygen saturation  has three separate CCD sensors to measure red, green and blue light intensity independently. We developed our own software for implementing image acquisition and processing on a Xilinx Spartan Field Programmable Gate Array (FPGA) board, using a workstation running the Fedora Linux Operating System. To comply with the requirements of our MREC approval and to preserve patient privacy, the images are stored using a customised binary format and saved in an encrypted storage cluster.Fig. Regular interaction between the clinical staff and the baby;Clinical interventions such as heel pricks, used to withdraw blood for lab tests;Baby taken out of the incubator to be held by the mother (kangaroo care).We label the stable periods of video data outside these occurrences as ‘valid camera data’. To identify these stable periods, we use a non-parametric statistical background image estimation algorithm based on the methods described in [One of the main goals of our study is minimal interference with regular patient care. There are therefore periods during which the video data cannot be analysed. These correspond to the following occurrences:ribed in  to classS, a rectangular area on the patient's skin, such as the face, head or neck, for which the changes in colour and volume with every heart beat can be estimated from analysis of the video signal and the background ROI, ROIR, from which the artefacts associated with strong light sources can be minimised, as described in [Once stable periods have been identified, two regions of interest (ROI) are computed: the subject ROI, ROIribed in .S, typically within a 150 × 150 ROI. We use independent component analysis (ICA) [The vital sign estimation algorithms start with the extraction of the mean intensity for the pixels from the three channels of ROIis (ICA)  of theseWe model the output of the ICA process with a set of auto-regressive (AR) models . AR modeBreathing-synchronous motion also modulates the amplitude of the reflectance PPG signal recorded by the video camera; hence, there is also a respiratory peak in the spectrum, but of much lower amplitude than the cardiac peak. The reflectance signal is filtered independently with an FIR band-pass filter (BPF2) tuned to the expected frequency range of respiratory rates in pre-term infants . This filtering approach to enhance the respiratory rate information is described in more detail in , with thThe cardiac and respiratory frequencies are enhanced using band-pass filters BPF1 and BPF2 applied to 8-second and 20-second windows, respectively, prior to modelling with standard low-order AR models .For oxygen saturation estimation, the sliding windows of the heart rate estimation algorithm (moved 1 s at a time) are analysed. As a validation step for now, only those windows for which the camera-derived heart rate estimates agree with the reference measurements (within ±2 beats/minute) are used to estimate oxygen saturation from the outputs of the red and blue channels, each filtered with BPF1.3We report the results from the first two of the infants monitored in our study for nearly 40 h in total. The recordings were made during the months of April and May, and data collection will continue until the end of the calendar year. As one of the main goals of our study is not to interfere with regular patient care, the video recordings are made within the unmodified environment of the NICU, which is a mixture of natural lighting and artificial lighting (mostly fluorescent). Changes in artificial lighting can affect the estimation of the vital sign values. We observed an aliased mains frequency peak at 10 Hz. As explained in our previous paper , pole ca3.1R-peaks in the electrocardiogram (ECG) and one derived from the beat-to-beat intervals between successive peaks in the contact PPG waveform (red channel from the pulse oximeter). After synchronising these two data streams, we investigated the agreement between the two heart rate estimates and found that 94% of the ECG-derived estimates and PPG-derived estimates were within ±4 beats per minute of each other. This gives us a measure of the error which we should aim for when comparing our camera-derived estimates of heart rate with the ECG-derived heart rate.There are two sources of heart rate information available from the Philips monitor: a measurement derived from the beat-to-beat intervals between successive b), we compare the camera-derived respiratory rate estimates with this re-derived reference.The situation is more complicated with respiratory rate. The electrical impedance pneumography (EIP) signal, obtained by injecting a high-frequency AC current between the pair of ECG electrodes across the chest, is notoriously noisy. In an attempt to validate the estimates computed by the Philips patient monitor, we acquired the EIP waveform and band-pass filtered it using a 10 second-long FIR filter with frequency cut-offs equivalent to 20 and 100 breaths per minute, the limits of the typical range of neonatal respiratory rates. Re-derived estimates of respiratory rate were then calculated by finding the peak in the power spectrum of 20 s sliding windows of this signal, updated every 2 s. (A 1024-point FFT with Hamming windowing was employed to estimate the power spectrum.) We found, on a typical 7-hour record, that just under 60% of the values for the IntelliVue MX800 monitor and the corresponding re-derived estimates were within ±10 breaths per minute of each other. In subsequent analysis  at two wavelengths is much more difficult than for the case of the video signals recorded in the adult study in the Renal Unit , mainly 3.2We next investigated the lengths of time for which we were able to monitor the infants continuously. Each infant was monitored on four consecutive days, for periods ranging from 4.14 to 7.32 h , apart from day 2 for Patient 1 . Table The ROIs used to derive the results are manually segmented from review of the beginning of the video recording and then automatically tracked as the baby moves . As showMajor changes in lighting conditions in the NICU.Variation in the baby's activity patterns. Small pre-term infants make irregular movements throughout the day, both during wakefulness and sleep, and these make it difficult to compute the frequency components of the heart rate and respiratory rate in the pulsatile reflectance waveform. These motion or activity patterns are not fully understood and we are planning to study them in greater detail, as they may be indicators of the baby's well-being.The lack of visible skin area. Although Fig. The above three factors combine to reduce the time for which we could estimate vital sign values accurately from 24.9 to 20.1 h . For those 20.1 h, we were able to obtain accurate estimates of heart rate continuously, using 8 s sliding windows. Estimates were deemed to be accurate if the root-mean square error (RMSE) between the camera estimate and the ECG-derived value (from the Intellivue MX800 monitor) was less than 5 beats/minute. Overall, for the data labelled as accurate according to this criterion, the RMSE with respect to the ECG-derived heart rate varied from 3.45 to 4.27 beats per minute for the 8 sessions (mean = 3.95 beats per minute). The mean absolute error (MAE) for the same 8 s windows varied from 2.23 to 3.14 beats per minute for the 8 sessions (mean = 2.83 beats per minute).However, even during stable periods, we found other phenomena that prevented us from estimating the vital sign values accurately. These include:3.3t = 14 min  around pSO2 value of 70%, which is tracked by the changes in the value of the DC ratio (red/blue).The plots of heart rate, respiratory rate and oxygen saturation, both the reference values from the Philips monitor (in black) and the video camera derived estimates (in red) are shown in Figs. Fig. It shows that 91.9% of the ECG and pulse oximeter values are within 2 beats/min of each other. The equivalent figure for the camera-derived values and the ECG or pulse oximeter values is 81.2%. If an absolute error of 4 beats/min is acceptable, the accuracy of camera-derived estimates is not significantly worse than those obtained with conventional monitoring, as demonstrated by the convergence of the three traces on Fig. The changes in oxygen saturation during the bradycardic episode are clinically important. The oxygen saturation that is estimated by calculating the ratio of the DC values of the camera PPG signal at the red and blue wavelengths is that of the blood present in the skin tissue of the pre-term infant being monitored. Tissue oxygen saturation is believed to be correlated with central arterial oxygen saturation and therefore with peripheral arterial oxygen saturation as measured with pulse oximeters . However4We have demonstrated that it is possible to monitor heart rate, respiratory rate and changes in oxygen saturation continuously in the NICU, with an accuracy which is clinically useful. To the best of our knowledge, this is the first study establishing the feasibility of continuous non-contact monitoring of cardiorespiratory vital signs in hospital using a digital video camera and regular ambient light, for several hours, without affecting patient care. We have now successfully monitored fifteen infants continuously during the daytime. We also believe that this is the first report of non-contact monitoring of oxygen saturation in the NICU using ambient light and a single video camera. We have shown that our algorithms for processing the camera reflectance signals are capable of identifying clinically important events such as a bradycardia accompanied by major desaturation.


Using our original technique, we measured erythrocyte intracellular ionized Mg2+ concentration (RBC [Mg2+]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg2+]i significantly correlated to hippocampus extracellular fluid Mg2+ concentration, and further correlated to hippocampal synapse density. Elevation of Mg2+ intake in aged rats demonstrated an association between RBC [Mg2+]i increase and memory recovery. The therapeutic effect of Mg2+ administration was inversely correlated to individual basal RBC [Mg2+]i. In summary, we provide a method to measure RBC [Mg2+]i, an ideal indicator of body Mg2+ level. RBC [Mg2+]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg2+-deficiency-associated memory decline during aging.Magnesium (Mg Mg2+ is a cofactor for more than 300 enzymatic reactions, responsible for conducting biomolecule synthesis/hydrolysis, signal transmission, and gene expression. It also binds to ATP to maintain its stability, and is therefore essential for energy metabolism. Mg2+ participates in important vital activities, such as cell proliferation, neuron spiking, and muscle contraction/relaxation, among others134Magnesium Mg+ is the 2+ also plays important roles. It competes with calcium (Ca2+) to mediate N-methyl-D-aspartic acid receptor (NMDAR)-dependent neural activity. Although Mg2+ blocks NMDAR at resting membrane potential, our previous study showed that, chronic elevation of Mg2+ level in hippocampal neuron culture medium upregulated NMDAR signal transmission and enhances synaptic plasticity2+ in brain function. However, our previous in vivo studies did not show any difference of endogenous Mg2+ level between young and aged rats. That means, although exogenous Mg2+ administration showed notable therapeutic effects on the memory recovery of aged rats, it was still not clear whether the memory impairment during aging was caused by endogenous Mg2+ level changes or not. In fact, all the figures which involved in the therapeutic effect of Mg2+ supply enhancement, whatever on the behavioral, cellular or molecular level, lack support of endogenous Mg2+ data2+ concentration of the cerebrospinal fluid (CSF [Mg2+]) after Mg2+ administration, in an independent experiment of exogenous Mg2+ delivery optimization. Yet, the evidence was far from enough. It requests further studies on the relationship between endogenous Mg2+ status and memory performance.In the neural system, Mg2+ marker for brain function and memory is a challenging task. Many Mg pools in the body could serve as potential candidates. The total Mg content in an adult human is about 1 mol: 60~65% of it is contained in the skeleton, 27% in skeletal muscle, 6~7% in other tissues, and 1% in extracellular fluid2+]i was found to be a potential Mg2+ index, which effectively represents body Mg2+ loss in the cases of hypertension and/or diabetes8910112+]i to study its capability as a body Mg2+ marker.To find an ideal Mg2+]i decline2+ deficiency may be caused by unhealthy dietary pattern132+ absorbance/clearance function151617101921232425262+ intake could rescue cognitive function in aged animals2+]i decline might correspond with memory impairment during aging. Therefore, we used aging rats as a model to research whether RBC [Mg2+]i could be a potential memory indicator.Aging was also associated with RBC [Mg2+]i and memory performance in aged rats. The level of RBC [Mg2+]i directly influenced memory status, when the supply of exogenous Mg2+ was changed in aged rats. The effect of abundant Mg2+ supply to improve memory was inversely correlated to the individual basal RBC [Mg2+]i in aged rats.In the present study, we found and confirmed a significant correlation between RBC i could act as an indicator for body Mg2+ status. Mg2+ intake deficiency was an ideal model for creating a dramatic Mg2+ change in a short term. The Mg2+ content in the blood, tissue, and skeleton has shown a decline in this model28293031322+]i was also a body Mg2+ marker, it would respond to food Mg2+ restriction too.For the purpose of studying the correlation between Mg2+ deficient food caused a dramatic drop in total Mg intake, from 22.5 ± 3.62 to 3.16 ± 0.56 mg/day , aged animals showed a significant decrease in recognition score comparing to young group, .The young rats performed better than aged rats in the 8 minute T-maze test . A lineaung rats , and the2+]i and memory appeared to have a tight connection. RBC [Mg2+]i was positively correlated with recognition memory as well as spatial working memory in aged animals, indicating that the RBC [Mg2+]i might be used to predict memory performance during aging. Aging caused widespread distributions in both RBC [Mg2+]i and behavioral performance , and then MgT was administered from week 0 to week 4 (Mg2+ on). From week 4 to week 5, a secondary measurement of RBC [Mg2+]i and a second T-maze test were conducted. This was followed by 4 weeks of normal Mg2+ intake to allow the body Mg2+ to return to normal level (Mg2+ off). At week 9, we did a final correlation test to study the effect of MgT withdrawal.A previous study reported that 24 days administration of magnesium-L-threonate (MgT), a highly bioavailable Mg2+ treatment successfully improved both RBC [Mg2+]i  to influence animal memory. The memory recovery effect was more pronounced in individuals with lower basal RBC [Mg2+]i levels, indicating the function of RBC [Mg2+]i to predict therapeutic effect of Mg2+ compensation during aging.In conclusion, RBC [Mg2+]i and memory. The same group of aged rats was used as in 2+] was previously reported to affect the function of hippocampal neuron culture2+ concentration in hippocampal extracellular fluid (Hip ECF [Mg2+]) was significantly correlated with the RBC [Mg2+]i in aged rats  puncta density was found in the dentate gyrus (DG) subregion of Hip (2+ (RBC [Mg2+]i), brain Mg2+ (Hip ECF [Mg2+]), and synapse density (8 different brain subregions), to memory performance (NORT and T-maze). The dark brown squares indicate the strongest correlations. Synapse densities in the dorsal and lateral striatum were used as controls, which showed no significant correlation with almost any of the other items.Immunostaining of synaptophysin was used to identify presynaptic terminus. The density of synaptophysin-positive (Syn-(+)) puncta was used to evaluate synapse density. A strong correlation between RBC i, was correlated with recognition memory and spatial memory in rats. The possible mechanism for this phenomenon was: the RBC [Mg2+]i represented the brain ECF [Mg2+] level, the latter affected the density of Syn-(+) puncta and ultimately regulated memory. We also confirmed the aging associated endogenous Mg2+ deficiency, and found that compensation of RBC [Mg2+]i deficiency by exogenous Mg2+ administration rescued the memory decline in aged rats. The Mg2+ administration selectively improved the memory of individuals with low basal RBC [Mg2+]i, showing an inverse correlation between basal RBC [Mg2+]i level and therapeutic effect. Our original technique for RBC [Mg2+]i measurement may provide a potential tool for clinical diagnosis and treatment of aging-associated memory decline.In the present work, for the first time, we found that endogenous Mg2+ index to indicate body Mg2+ status. Our focus on the blood Mg2+ pool has many advantages. First, blood samples are very easy to collect, causing little hurt to animals, allowing real time and repeated assays. Second, blood regulates the Mg2+ content in tissues of the whole body through Mg2+ exchange, which raises the possibility that blood [Mg2+] could represent the Mg2+ levels in other tissues. Third, the role of blood Mg2+ as a biomarker in peripheral diseases is well established. Some reports have already shown significant changes in blood Mg2+ pools in hypertension and diabetes patients  is the real Mg2+ component with the most bioactivity, which regulates intracellular physiological reactions and exchanges Mg2+ content with extracellular plasma pool. Thus, the [Mg2+]i of erythrocytes might represent the Mg2+ status of blood cells and might further correlate with the body Mg2+ status.Blood Mgsyndrome , and fai2+]i corresponded to other blood Mg2+ pools during body Mg2+ decline in the processing of hypertension/diabetes8910112+]i not only correlated to the Mg2+ levels in peripheral tissues, but also correlated to brain ECF [Mg2+]. A further correlation between RBC [Mg2+]i and memory was found, which still persisted when RBC [Mg2+]i was adjusted by Mg2+ intake “on/off”. Our findings redefined the biomarker function of RBC [Mg2+]i: not only being a Mg2+ marker in the periphery, but also being a memory indicator in the CNS.It has been previously reported that RBC  was significantly correlated with the density of Syn-(+) puncta in different subregions of the Hip, with the strongest correlation found in the DG. The synapse density in the DG was further correlated with the recognition and spatial memory, in agreement with earlier work7Although above evidences suggested a possible function of brain Mgpocampus ,d. The HThe mPFC also plays an important role in learning and memory. The synapse density in the PrL subregion was the most strongly correlated with memory. The striatum was reported to influence the transformation of space/response acquisition strategy in the T-maze test2+]i, ECF [Mg2+], synapse density, and memory are correlated with each other. The blood and brain ECF exchange Mg2+ through the BBB. While the brain ECF [Mg2+] regulates synapse density in the Hip and mPFC functional regions, further modulating recognition and spatial memory functions. During aging, a degenerated Mg2+ metabolism from the periphery to the brain leads to downregulation of synapse density and impairment of memory. Exogenous administration of Mg2+ could rescue these symptoms. The utilization of RBC [Mg2+]i assay provides an easy, repeatable, and representative technique in the fundamental research for studying the role of Mg2+ in neural activity and memory function.With above findings, we have constructed a logical model . The RBC2+ supplementation experiments in aged rats showed that RBC [Mg2+]i and memory corresponded with each other during the Mg2+ “on/off” periods, which highlighted the correlation between these two items. Modification of the body Mg2+ status directly affected the behavioral score, which suggested not only the associated relationship, but also the subjective role of the endogenous Mg2+ level to influence memory. This finding may help in clinical studies of the Mg2+ therapy for preventing endogenous Mg2+-deficiency-associated memory decline during aging.The exogenous Mg2+ intake sufficiently rescued the memory decline in individuals with low basal RBC [Mg2+]i, whereas aged rats with normal baseline RBC [Mg2+]i levels were not affected. This finding reflects two facts. The first is, not all aged animals have endogenous Mg2+ losses and memory decline. Aging is not stringently corresponding to the degeneration of memory function, but only increases the risk; while RBC [Mg2+]i, at least on our experimental platform, shows a strict correspondence with memory performance, making itself a more precise memory indicator. From this perspective, in the studies of aging associated memory decline, it is not enough to define “aging” with only “how many years old the subject is”; but a differentiation of the individual RBC [Mg2+]i levels is also required. Using “Mg2+ age” to delimit “aging” and memory deficit is more representative . For Mg2+ intake deficiency experiment, 3-month-old rats were used (n = 10). For other experiments, young (3 month) and aged (22 month) rats were used (n = 14/group).Male Sprague-Dawley rats were obtained from Vital River Laboratory . All animals were housed individually, with free access to standard food and water, in a controlled environment , under a 12:12 hour inverted light-dark cycle (light off from 8:00 A.M. to 8:00 P.M.). On arrival and during the whole experiment process, rats were fed a commercial pelleted diet , containing a normal MgAll experiments involving animals were approved by the Tsinghua University committees on animal care. All the methods were carried out in accordance with the approved guidelines and regulations.2+ deficient diet  was composed of 180 g/kg casein, 100 g/kg sucrose, 588 g/kg cornstarch, 30 g/kg α-cellulose, 50 g/kg soybean oil, 2 g/kg methionine, 40 g/kg mineral mix, and 10 g/kg vitamin mix. The total elemental Mg2+ concentration in the Mg2+ deficient food was 0.003% (compared to 0.15% in standard diet), as determined by inductively coupled plasma atomic emission spectrometry .The Mg2+ intake deficiency test, two groups of rats were fed with either standard food or Mg2+ deficient food for 4 weeks. Rat chow was weighed to calculate the daily total Mg intake. A body Mg retention test was also assessed during this period  containing 0.5 mmol/L Mg2+. A cell-permeable Mg2+ dye, Magnesium Green , was used to detect RBC intracellular free Mg2+, with a working concentration of 5 mg/L. Pluronic F-127 (Invitrogen) was used to aid dissolution of MaG. The mixture of RBCs and MaG was incubated at 37 °C for 60 minutes, washed twice, and incubated at 37 °C for another 30 minutes. The fluorescence signal was detected by flow cytometry . The erythrocyte population was gated by forward scatter (FSC)/side scatter (SSC) dotted diagram. A total of 1 × 104 erythrocytes in FL1 were selected for average fluorescence intensity (2+) and then mixed in HBSS with a gradient of [Mg2+]. A23187 (Sigma-Aldrich) was used to maintain the external and internal [Mg2+] balance across the cellular membrane, with a working concentration of 25 μmol/L. Mixtures were incubated at 37 °C for 2 hours and then analyzed by flow cytometry. A fitted curve was built using fluorescence intensity as x-axis and standard [Mg2+] gradient as y-axis  to MaG fluorescence was also evaluated . Data were analyzed by dividing the tissular total Mg of each rat in low Mg diet group with average tissular total Mg in normal Mg diet group, as below:2+], rats were anesthetized with chloral hydrate  and CSF was collected from the cisterna magna using a 1 mL syringe. The Mg2+ level in CSF was determined by calmagite chromometryFor determination of CSF [Mg2+], rats were anesthetized with chloral hydrate  and positioned onto a stereotaxic apparatus. A midline incision of the skull was executed and a small hole was made in the skull using a dental driller. A microdialysis guide cannula (CMA) was implanted into hippocampus . The guide cannula was fixed with light-solid dental cement. The rats were allowed to recover for 1 week before in vivo microdialysis sampling. During sampling, a microdialysis probe  was inserted into the guide cannula in anesthetized rat. Artificial CSF solution (aCSF) was perfused at a flow rate of 0.2 μL/minute, for at least 30 minutes for equilibration. Samples were continuously collected for 2 hours on ice. The Mg2+ level in the ECF was determined by calmagite chromometry.For determination of extracellular fluid (ECF) i.The testing sessions were the same as training sessions, except that the delay interval time was extended from 15 seconds to 4 or 8 minutes. For correlation analysis, the 8 minute delay test was repeated for 3 consecutive days, with a total of 24 trials for each rat. Rats used space rather than response acquisition strategy when the maze was rotated 180° (data not shown). After the T-maze test, blood samples were taken to determine RBC [Mg2+ treatment procedure, MgT was administered via the drinking water . This Mg2+ compound was highly bio-affinitive and successfully increased the Mg2+ in rodent brain via dietary supplementationIn the MgThe procedures for brain perfusion, brain fixing, slice cutting, and immunostaining were described before3. The density of synaptophysin-positive puncta was estimated from the obtained images using Image-Pro-Plus software version 6.0 (Media-Cybernetics). Background levels were equalized and special filters were applied to separate fluorescent puncta. Settings for each image were adjusted to maximize the number of detected fluorescent puncta. The mean punctum number/μm2 was used as an estimate of the presynaptic punctal density.The synapse density could be estimated by immunostaining of synaptophysin (Syn), which binds to the vesicles at the presynaptic release site, and participates in synaptic transmission. Measurement of Syn-(+) puncta can be used for the quantification of synapses. The procedures for confocal scanning and signal processing were described previouslyt tests. Correlations were analyzed using linear regression. The T-maze retention interval curve was analyzed using two-way ANOVA, followed by Bonferroni’s post hoc test. The Mg2+ “on/off” experiment was analyzed using one-way ANOVA, followed by Bonferroni’s post hoc test. Statistical significance was defined as p < 0.05.Data are presented as mean ± SD. All data comparing two groups were analyzed using unpaired How to cite this article: Xiong, W. et al. Erythrocyte intracellular Mg2+ concentration as an index of recognition and memory. Sci. Rep.6, 26975; doi: 10.1038/srep26975 (2016).