The inaugural winner is Dr. Serafim Batzoglou , ProfessCosmos television series. These early experiences nurtured his interests in math, physics, and computer science, and Batzoglou went on to earn two bachelor of science degrees in mathematics and computer science at the Massachusetts Institute of Technology (MIT). Batzoglou also encountered computational biology for the first time as an undergraduate. He says, “Upon entering college, I was deciding between two fields of study that had fascinated me during high school: astrophysics and artificial intelligence (AI). However, during the early 90s, I felt that neither physics nor artificial intelligence was experiencing any exciting growth. At least, that was my impression around 1995, when I had been admitted to a PhD program in computer science at MIT and was deciding on an area to focus on. I took Bonnie Berger and David Gifford’s class on computational biology and felt that this was a research area with great potential where I could apply my computer science background to do science (rather than engineering).” Batzoglou credits his early mentors for giving him invaluable undergraduate research experiences, including Sorin Istrail, with whom he had a very enjoyable research summer during 1997, and his undergraduate research supervisor David McAllester.Batzoglou remembers having an early fascination with numbers and a sense of wonder about the universe around him as a young child. He recalls, “I was interested in math and science for as long as I can remember. Before going to preschool, I remember counting and adding large numbers as well as wondering how big space is and where it ends.” Batzoglou’s curiosity was stoked by other cultural touchstones, including the novels of Jules Verne and Carl Sagan’s captivating Batzoglou went on to earn his PhD in computer science at MIT under the mentorship of his advisor Bonnie Berger and co-mentor Eric Lander. During his early career, he was the lead algorithms designer and implementer of ARACHNE, one of the first programs for whole genome shotgun sequence assembly that was used for assembling several genomes, including the mouse and dog genomes. Batzoglou’s early work included using comparative genomics for human gene identification. Together with his collaborators, he developed multiple genome alignment tools, including LAGAN, and applied these tools to predict human genes from similar mouse genes. This work was significant to the emergence of the field of comparative genomics and its applications for identifying genes, regulatory regions, and evolutionary events, as well as other features across species.Batzoglou and his lab focus currently on the development of algorithms, machine learning methods, and systems for the analysis of genomic data. He recalls one of his more surprising research moments that stands out in his memory: “It was unexpectedly good news to me back in 2005 that Conditional Random Fields (CRFs) and similar flexible models that can learn very large parameter sets could be so successful in a large variety of classic computational genomics problems, including RNA secondary structure prediction, gene finding, and sequence alignment. My line of work on CRFs, together with my PhD students at the time, Chuong Do and Sam Gross, who led the effort, was when we began applying machine learning in earnest to genomics problems.”Batzoglou aims to follow the example of his PhD mentor as he mentors students and postdocs in his lab: “I think I follow a similar style and philosophy as my PhD advisor, Bonnie Berger, in that I am supervising my students in a relatively hands-off, ‘first do no harm’ manner and, to the extent possible, allow them to define new research topics and directions.” He also looks forward to a time when more novel research can be supported through the grant system, saying: “The most talented and motivated students will do their best research when given freedom, encouragement, and some resources. I would be supportive of a large fraction, say 25%, of the government funds to be earmarked for work on new directions—i.e., work on which the proposing PIs [principal investigators] have no other funds and no related papers.”Batzoglou’s novel research contributions have been recognized through several awards, including being named among the Top 100 Young Technology Innovators in 2003 by MIT’s Technology Review Magazine and a 2004 NSF CAREER Award. His research publications alone also show his impact on the field, and his purely bioinformatics-based publications have been cited hundreds of times. Batzoglou has also served the computational biology community in numerous capacities, especially through his service as a member of the steering committee and his service as a program chair, session chair, and organizing committee member for various RECOMB and ISMB meetings.Looking forward, he says, “The topic I am most fascinated by right now, although it hasn’t majorly influenced my research yet, is deep learning. Like many of my AI colleagues, I subscribe to the opinion that we are witnessing a major breakthrough in our ability to replicate (and improve on) a large fraction of the intellectual and perceptual capacity of humans. The victory of AlphaGo against Lee Sedol is a historic moment. From a personal perspective, I learned Go in 2003, and back then I considered it a midpoint in AI between where we were and full-blown human-level intellectual capacity . The significance of advances in AI cannot be overstated. I believe that AI will transform medicine, finance, construction, manufacturing, commuting and transport, and almost every other sector in society over the next 20 years. I also believe that a large fraction of jobs in these fields will be made redundant. Re-education is great, but it is not clear at all what the new marketable human skills will be 20 years down the line. Perhaps anything involving human interaction, although that’s not clear. In terms of computational genomics and biomedicine, to the extent that we will be able to collect and agglomerate large genomic and biomedical datasets, application of AI will lead to breakthroughs that will start by vastly improving health care, agriculture, and biotechnology, and continue to places that are hard to imagine today.”Batzoglou feels greatly honored to be selected as the inaugural winner of the ISCB Innovator Award, and says, “Innovation in computational biology—and in general—is largely a community process. I thank the committee for recognizing my work, and more importantly, I thank my colleagues, mentors, and foremost my students, with whom I should be sharing this Award.”


Rural men are known to have poor health behaviors, which contribute to their elevated burden of cardiometabolic disorders in the United States. Although regular physical activity, healthy eating, and avoiding tobacco can reduce cardiometabolic risk, little is known about how to engage rural men in health promotion programs. To bridge this gap in evidence, we investigate knowledge of modifiable cardiometabolic risk factors among rural men in the western United States, identify their concerns related to heart health and motivation to reduce risk, and explore individual, social, and community-level influences on heart-healthy behaviors, specifically diet, physical activity, and tobacco use.We conducted seven focus groups with 54 sedentary, overweight/obese men (mean body mass index [BMI] = 31.3 ± 4.6) aged 43–88 residing in government-designated “medically underserved” rural Montana towns in September and October 2014. All sessions were audio-recorded and transcribed verbatim. Transcripts were coded and analyzed thematically using Nvivo software. Participants also completed a brief questionnaire about personal characteristics and health behaviors. These data were explored descriptively.Despite being classified as overweight/obese and sedentary, no participants reported to be in poor health. Many men described health relative to self-reliance and the ability to participate in outdoor recreation; concern with health appeared to be related to age. Participants were generally knowledgeable of heart-healthy behaviors, but many felt fatalistic about their own risk. Catalysts for behavior change included a serious medical event in the household and desire to reduce aging-associated functional decline. Barriers to adopting and maintaining healthy eating and physical activity habits and abstaining from tobacco included normative beliefs around masculinity and individual liberty, the limited social universe of small towns, winter weather, time constraints, and preferences for unhealthy foods. Facilitators included behavioral self-monitoring, exercising with a partner, and opportunities for preferred activities, such as hunting and team sports.These findings provide important insight about influences on rural men’s health behaviors and provide guidance for possible intervention strategies to promote cardiometabolic health.NCT02499731. Registered 1 July 2015.ClinicalTrials.gov  Cardiometabolic disorders, including cardiovascular disease and type two diabetes, are the leading causes of disability and death globally. In the U.S., approximately one in every three adults has cardiovascular disease  and moreGeographic inequalities in health have widened in recent decades –6 and reEvaluation of successful health behavior change interventions has provided evidence on effective strategies to improve physical activity levels, dietary habits, and tobacco behaviors; yet men have been underrepresented in the research –18 and tThe purpose of this study was to determine knowledge of modifiable cardiometabolic risk factors among men living in Montana, identify their concerns related to heart health and motivation to reduce risk, and explore individual, social, and community-level influences on heart-healthy behaviors, specifically diet, physical activity, and tobacco use. Montana is the fourth largest state by area in the U.S. and one of the most rural. The most recent U.S. Census documented 6.8 persons per square mile compared to the national average of 87.4, with 44.1 % of residents living in rural areas (clusters <2500 people) . The staWe conducted seven focus groups in six government-designated medically underserved  rural MoAt each site, National Institute of Food and Agriculture (NIFA) Extension agents recruited a purposive sample of overweight, sedentary men aged 40 and older, using a variety of community-based strategies, including press releases, flyers, and website posts. We determined eligibility using a brief screening tool that asked men to self-report age, height, weight, and activity-level. We defined sedentary as participating in no more than one bout of 30 min (or more) of physical activity per week, on average, over the past three months. Focus groups were held at local community sites and stratified by age .An experienced focus group facilitator (MLG) led the sessions, which lasted between 60 and 90 min. The discussion guide was informed by the socio-ecological model and developed by MLG, SCF, and RAS . The questions explored awareness and knowledge about factors related to cardiometabolic risk; access to health care services and information; attitudes, perceptions, barriers, and facilitators to heart-healthy behaviors; and understanding community in a rural environment. We conducted a pilot focus group in Ithaca, NY and subsequently refined the guide to improve question comprehension and discussion flow. In addition to participating in the discussion, we asked participants to complete a brief questionnaire that asked about demographic characteristics and health behaviors. Participants received $50 compensation. The Institutional Review Board at Cornell University approved all protocols and materials (Protocol # 1402004505) and all participants provided written consent to take part.Focus groups were transcribed verbatim and EHM reviewed transcripts against audio-files for accuracy. All transcripts were imported into NVivo version 10  and coded by question. We developed an initial descriptive coding framework based on the main focus group topics and themes that emerged during transcript reviews. Two people independently coded a subset of the data and reviewed coding decisions line-by-line. Inter-rater reliability was high, with observed agreement >95 % and prevalence- and bias-adjusted kappa >0.90. We resolved differences in interpretation by discussion and added additional emergent themes to the framework. EHM, who has expertise in qualitative analysis, then recoded all transcripts using the revised framework. Further coding was an iterative process grounded in the data. Data were triangulated by comparing the comments of participants within and between groups and analyzed by descriptive and thematic analyses. Survey data were tabulated using SPSS, version 22. We conducted all analyses in 2015.In total, 54 men, aged 43–88 years, participated. All were White, non-Hispanic and, reflecting the demographic characteristics of the communities, most were married and had a household income under $75,000 Table . Over onFindings from the focus groups are divided by research objective. Themes and subthemes that emerged are described in the text and illustrated with quotes.Across the study communities, participants were generally aware of the modifiable risk factors for cardiometabolic disorders, particularly weight status, smoking, and stress. The men described several types of physical activity that were good for their hearts, including walking, mowing the lawn, chopping firewood, sex, and caring for livestock. While some mentioned structured exercises, such as running, fitness classes, or weight lifting, most felt “anything that gets your heart rate up” was beneficial.“You ever watch the Dr. Oz show? Boy, he’s good. But, God-dang, every other day it’s, ‘This is better, this is better, you know the red, the white, the green, the purple, this fruit, that fruit – you know this [is] where you get your antioxidants, and, you know, this is way too fattening, don’t put any salt, don’t put no sugar, you can get lots better…’ You know, I’m goin’, ‘Oooh, wasn’t it just last week that it was the other way around?’” Participants in all focus groups identified a number of foods as heart-healthy, particularly fruits, vegetables, whole grains, and lean meats. Locally produced foods, including beef, wild game, and vegetables from home gardens were considered particularly nutritious. However, several men said that they felt confused about which foods are healthy due to conflicting media reports.“[My dad was] 42 years old when he had his first heart attack. And then he had another one at 43. He was overweight and smoked a pipe all his life. Probably had bacon and eggs most every morning for breakfast… And stress: both times he had a heart attack, it was right in the middle of harvest and, you know, it was a stress-related thing too.” Participants were well-informed about the cardiometabolic risk associated with smoking and emphasized the role of information campaigns and knowing someone with a smoking-related health condition in raising awareness. In four focus groups, men discussed the link between stress and heart attack risk. Self-employment in agriculture was described as demanding and unpredictable, and managing stress was considered critical for maintaining heart health.“I’m morbidly obese, but when I go in and get a check-up, the doctors all come out and remark that they wish they had my lipid profile… But I have a niece who got left a widow with two small children and her husband was 32 years old when he died, a farmer, died of a heart attack, and no previous evidence of trouble. And here turns out his dad died at 32 years of age… so, you know there was something there, in that, you know, in their genetics or their makeup of their heart that it just didn’t have that many miles in it, and you know bang it’s, it broke.” Despite being knowledgeable of modifiable cardiometabolic risk factors, many participants were fatalistic regarding their risk of a heart attack or stroke, often attributing it to family history or luck. In six focus groups, men shared personal experiences or anecdotes of people they knew who had a cardiac event despite living a healthy lifestyle or of people who had high-risk behaviors and nonetheless enjoyed long, seemingly healthy lives.“Ya know, when the doctor said, “Guess what, you’re a diabetic,” then you really don’t have any choice but to change the way you eat, because if you go and eat a big old slice of cheesecake or something, your blood sugar is not going to be under control. Sorry.” “I had ‘ta work really hard in losing more weight, because… I had a total knee replacement, and, for my age that I had it at, you know, the average knee lasts maybe 10 to 12 years… and I’m tryin’ to get the most out of my knee.” “For me, [my greatest health concern is] just getting old… The things that I do today, I’d like to be able to do when I’m 75 or 80. And that’s what kind of motivates me to try to take care of myself right now, but whether that’s going to pay off, who knows.” Health was a priority for some but not all participants and concern appeared to be related to age. Several men said that they were motivated to change their behavior following a serious medical event  or disease diagnosis  within their household; they also were motivated by a desire to reduce aging-associated functional decline. Several participants expressed admiration for older men who were capable of strenuous work, particularly chopping their own wood and hunting on foot – activities that were closely associated with fitness and health – and an aspiration to be able to carry out those activities as they aged.“In different places I worked, you know long after they banned smoking… [they] had a sign in the back [of the] bar, you know, that said ‘Montana, where you could still drink in your car and smoke in the bar.’ And, and that was true for a long time until Montana finally got forced to get on board with the open bottle law. I mean you could never legally drive drunk, but if you weren’t drunk, you could have an open can of beer in the truck out on the prairie or somethin’.” “Now I think folks that live like in this kinda country and Montana in general are relatively independent by nature, so if somethin’ does come up it makes you a bit bullheaded, like, ‘I could tough it out.’ And, that’s not the best answer, always, to tough it out.” Men expressed a great degree of pride in their communities and culture. Popular perceptions of western men as rugged, stubborn, and self-reliant were emphasized and interrelated with thoughts on public health measures. Government involvement in daily activities was generally unpopular. Social norms were represented as fundamentally at odds with health promotion. In fact, many participants boasted about their rejection of healthy behaviors, such as avoiding medical care. Persevering through pain and illness appeared to be venerated and could actually increase a man’s status. For example, in one group, participants expressed respect for a community member who has “got cancer real bad” but is “still getting out in the woods.”“I wanna clean my body out, I wanna quit smoking, ya know, I wanna quit drinking. Well, I mean, to be able to do stuff like that you pretty much have to change your friends at that point in time. And like in this town, who [are] you gonna change your friends to? Ya know, it’s not like you have 900,000 other people that you can go out with and visit with.” Some men related how, with few chances to meet new people, making a major behavior change could have profound implications on their social and professional lives. For example, men in one group said avoiding bars – a key location for social and business activity in town – could result in isolation and lost income.“To improve my health, for me, personally, exercise would be a big one. In the winter… I think all of us are pretty active in the fall and one of the things that attracts us here and keeps us here is hunting and fishing. But, you know, Thanksgiving weekend, that’s all done for the year, and ya get [a] pretty bad case of cabin fever about the end of January…” Montana’s natural environment was characterized as an outdoor playground with endless opportunities for physical activity in the warm months. Many participants reported enjoying outdoor activities that they believed had a purpose beyond simply leisure, particularly hunting and fishing. However, winter was described as a major barrier to being active. Although men in most communities identified at least one indoor space suitable for physical activity, these often were described unfavorably.“I have an app on my smartphone for your pace, you know, steps you do. And I look at that periodically through the day. Because I have a goal I set on that… You know, I’m a farmer and so, you know, instead of just taking the four-wheeler, I just walk, you know, just to get my extra steps or something.” Despite some groups discussing how increasing mechanization on farms made their work less physically demanding, ranching was still juxtaposed with sedentary “desk jobs.” Participants said that they did not have time or interest in participating in structured exercise, which was described by some as a leisure activity for rich, single men, typified as “trust fund guys.” Instead, physical activity was viewed as a natural part of daily routines and could be increased by finding ways to build more activity into their usual schedule, possibly by learning techniques from each other. In one group, two men suggested that self-monitoring using an activity tracker could be helpful.“[Hunting] starts pretty early in the year – unless you want to shoot gophers – and then it starts up again in September, so a lot of us who like to hunt have to get ready for it. So it’s a way of exercising at least.” Several men said that they disliked structured exercise or did not have the “willpower” to do it. However, getting in shape to participate in preferred activities emerged as a motivation for exercise.“I participated in a working out [group] when they were over here by the school. And, I don’t know, working out… First I forgot that the individuals that I was working out with were a generation or so younger than me and I thought ‘Oh man, I’m working out with all of these good looking women.’ Well, after five minutes into it I didn’t care. All I wanted to do was get the hell out of there and not die or throw up. (Group laughs.) So, it would be kind of interesting to have, I don’t know, some kind of organization for folks in our general shape, in our age bracket, you know, without a drill-master with a whip on us to give us some direction on how to properly work out and so forth and so on.” Some men also indicated that a group context incorporating an element of competition would be motivating. Men in one group said that working out in a group would encourage them by increasing “accountability to somebody else” and allowing them to “share some ideas” with each other, but would make them feel uncomfortable if the group was not targeted to their fitness level.“A lot of us live out of town, so the idea of coming back to town twice a week isn’t really appealing, unless there was a program that could be designed that is compatible for a man and wife to kinda try to do together. That might work for a big part of our community, ‘cuz of the distance and inconvenience of coming back and forth to town or something.” Living out of town emerged as a barrier to participation to group-based physical activity. Many men who lived outside of town did not want to travel to town to participate in something on a regular schedule. Participants in one group suggested that men might be more inclined to take part in a program that met less frequently, but integrated at-home activities that couples could do together.“A steady diet of just beef is not good, but a vegetarian diet is not living life.” Participants often indicated a preference for calorie-dense, animal-source foods and expressed the opinion that “healthy” foods are less tasty. For instance, in describing a heart-healthy diet, men in three focus groups cited the adage, “if it tastes good, spit it out.” Participants considered meat, generally accompanied by potatoes, to be the most important meal component. While some articulated the benefits of increasing consumption of fruits and vegetables, this generally did not imply a shift away from meat-based meals. In addition, healthy eating was associated with giving up favored foods and more laborious food preparation.“My wife gardens. You know, we eat a lot of fresh vegetables just because we would rather grow our own if we can, so we know where it came from.” “Sometimes the lack of choice at the local market can be kind of challenging. [The store owner] knows the market real well, so I don’t blame them for not putting things on the shelf that are going to rot and they end up throwing them away.” Hunting and fishing were described as major sources of meat and, in four groups, men reported that they or their wives were involved with growing their own vegetables and fruits during the summer months. However, local grocery and restaurant options for fresh produce were described as limited, overpriced, and of poor quality.“Like I said, you know, my wife. I always said that. I mean, she does the grocery shopping. I mean, she makes my lunch every day and makes breakfast and kind of, you know, I don’t say much, ‘cuz she could say, ‘Well, if you don’t like it, make it yourself.’” Some men felt that healthy eating in a social context was challenging, because of few healthy choices and the social expectation that they would accept food that was offered to them.Cooking was described as a highly gendered activity carried out almost exclusively by women. However, participants in two groups indicated that they enjoyed cooking and would be interested in taking cooking classes.“In terms of healthy eating, I went through the [Healthy Lifestyles Program]… and I find that [it] did stick with me and it was very simple. All I had to do was count grams of fat and keep them to a pre-set number based on my size, blah, blah, blah. And it worked… I’m still monitoring fat intake basically to this day and that was probably two years ago, or at least for me, it was probably two years ago. So, that definitely made a difference. And it’s not that easy to just cut fat out of your diet. It’s the good stuff, it’s the good-tasting stuff.” Some men reported participating in a state-wide dietary behavior change program and said that they found it to be helpful in changing eating habits through its emphasis on tracking and self-monitoring total fat intake. One participant specified that, to be credible, dietary educators should be “bigger around than my little finger.”“[In] the ranching community, there’s a lotta chewers, I think. Just,’cuz, when you’re out in the wind in this country, you can’t light up a cigarette, you know, and smoke. Or when you’re handling hay, you’re workin’ in the barn, you can’t smoke, but you can chew…” Men described tobacco use as common in their communities and associated chewing tobacco with ranching. Although most felt rates of smokeless tobacco  use remained high, participants agreed that smoking had declined in recent years and attributed this shift to increased awareness and the state-wide indoor smoking ban. However, a few participants suggested that tobacco use may be rising among youth.“I quit smoking when I was 21 years old. The problem was not the quitting smoking, it was the friends that still smoked, ‘cuz [when] you get around people that do smoke when you’re trying to quit, it’s very hard.” “Four or five years after I quit smoking, the salesman come and was talking insurances and stuff. He handed me a cigarette, I had it in my mouth, and he’d lit his, and he’d started to reach over there for mine, and I thought, “What!” I pulled that cigarette out of my mouth and it was just as normal as the day I quit smoking to get that thing and oh boy. (Laughs.)” Many men talked about the addictive properties of tobacco products and detailed their own struggles or those of their friends and family in quitting smoking or chewing. Quitting smoking was framed around an individual’s “willpower,” although living or socializing with smokers were acknowledged to be barriers.“I started smokin’ to quit chewin.’ It helped me quit chewin’. I’ve been chewin’ since I was 12 years old.” Several participants said that it was common for men in their communities to start using smokeless tobacco as a strategy to quit smoking, or to start smoking to quit chewing. Some participants also talked about eating a lot of candy after giving up smoking.This study examined the factors that influence physical activity, diet, and tobacco use behaviors in rural men, a group at elevated risk for cardiometabolic disorders. To our knowledge, this study is the first in-depth exploration of knowledge, concerns, and influences on heart-healthy behaviors for rural men in the western U.S. The results suggest this population is generally knowledgeable about modifiable cardiometabolic risk factors, but skeptical about the degree to which risk could be reduced by adopting healthy behaviors and confronted by considerable barriers to taking action. We believe these findings are relevant not only to rural men in Montana, but also to those in the bordering states of Idaho, North Dakota, South Dakota, and Wyoming, where demographic characteristics are similar , large pOverall, strong normative beliefs around rural masculinity clashed with public health goals. Rural men were characterized as “tough guys,” who work with their hands, hunt their own food, struggle against the odds to keep their farms and ranches viable, and consider seeking help a sign of weakness. Consistent with previous research , 27, an We found participants to oppose being told what to do and to resist restrictions on their behavior, but open to making changes if those changes were on their own terms. For instance, tracking and self-monitoring diet and activity were considered acceptable and appear to have been helpful to participants who have trialed them. Health was considered an individual responsibility and behavior change was perceived to be feasible by anyone with sufficient motivation. These sentiments should be taken into account when designing interventions targeted at rural men. However, participants’ acknowledgement of the critical role of their social environment in influencing health behaviors suggests a need to also engage rural men’s friends and family in promoted activities. Contrary to previous research with rural Latino and African American men , 20, parDespite increasing mechanization in agriculture, participants generally felt that they had sufficient opportunities to build physical activity into their daily routines. They overwhelmingly preferred to get their exercise from outdoor activities – particularly hunting and fishing – and cited winter as a major barrier to being active year-round. Group-based exercise was perceived more favorably than individual activity, in part because it provided scope for competition and social accountability. However, participants stressed that they would not take part if they felt uncomfortable or if frequent travel was required. Messaging focused on preparing your body to be in optimal shape for hunting or to participate in a team sport may be appropriate and effective for this population.Taste preferences and social norms around meat consumption emerged as major barriers to dietary behavior change. The popular perception that men need meat to complete a meal –31, was Men in this study clearly understood the benefits of avoiding tobacco and perceived smoking cessation to be socially desirable. However, many doubted that they could stop smoking and successfully abstain from tobacco, especially when continuing to socialize with tobacco users. Although prevalence of smoking has dropped substantially in recent years, several states continue to have high rates of smokeless tobacco use, including Montana and each of its bordering states . In factOur findings must be interpreted in light of several limitations. While men were recruited from the community, they self-selected to participate, and thus may not be representative of all overweight, sedentary rural men in terms of their understanding of and ideas related to cardiometabolic health. In addition, the screening tool relied on self-report measures of weight, height, and physical activity, and research suggests men tend to under-report weight and over-report height  and adulThe results of this study suggest that individual preferences, normative beliefs related to masculinity, and limited access to healthy food and activity options during the winter are important determinants of health behaviors in rural men in the western U.S. These findings provide guidance for possible intervention strategies to promote cardiometabolic health in this population. Future public health interventions could leverage messages that resonate with rural men, such as the benefits of healthy behaviors to maintaining physical function, foster family and peer support for positive behavior change, and support policies and programs that improve the accessibility and affordability of healthy foods and group exercise classes for men. For example, low-cost exercise sessions that focus on self-monitoring and keeping one’s body in shape for hunting and working outside may be of interest to this population. Overall, more intensive efforts are needed to engage men, particularly rural men, in chronic disease prevention interventions, and to design programs that suit their needs and preferences.Due to the small size of the communities where we conducted the focus groups and ethical considerations related to participant confidentiality, it is not possible to make data from this study publically available.


Tara Oceans project emerged from an early romantic idea I had in 2000: organizing a sailing expedition in the wake of Darwin's voyage aboard the Beagle to popularize Biology. The original concept was mostly educational and media-oriented. Many years later, in spring 2007, with the help of a few colleagues, a scientific dimension was added to the project, which was key to start motivating funders. The long search for support and for a suitable sailing vessel was finally successful, when in fall 2007 Eric met Etienne Bourgois and agnès b., the founders of Tara Expeditions. This non-profit organization runs the 110-foot polar exploration schooner Tara since 2003, participates in scientific expeditions and promotes environmental awareness with a very efficient communication and artistic program to reach the public. Both the idea of a 3-year around-the-world expedition to study pelagic plankton organisms and the urge to raise awareness about the serious environmental issues affecting oceans appealed to the organization. The synergy that would result from combining a solid scientific concept with a vigorous communication strategy convinced both parties to engage into a long-term commitment.The Together with a few adventurous colleagues, the first scientific meeting to plan the expedition was organized in Villefranche-sur-Mer in fall 2008. Inspired by the structure and functioning of EMBL, coordinators for various specialties were appointed. Specialists for the main domains of life  were needed, as well as oceanographers, ecologists, molecular and cellular biologists, physicists and bioinformaticians, including experts on imaging, databases and sequencing. Each of the scientists involved in this early phase recruited additional colleagues in a wonderfully self-organized process. With input from the different disciplines, we determined sampling zones, organisms' size fractions to be collected, and strategies for sample storage, handling and dispatching. Using a sophisticated bar coding system, high-quality environmental data were linked to biological samples. The early discussions were passionate and robust debates ensued. At times, we wondered whether we would make it. But with the increasing awareness of the exceptional scope of this project dedicated to the study, an entire biome at a planetary scale, a sense of great excitement and uniqueness started to diffuse throughout the growing consortium.Despite having first-class seed funding in the form of the boat, securing further financial support for the planned scientific projects turned out to be a considerable challenge. By the nature of its approach and its goals, the project was outside of the usual boundaries of funded scientific research. Since the consortium mostly consisted of European researchers, we first solicited the European Commission, without success, as our project did not fit into existing calls, and preparation of new ones takes time. We also faced strong skepticism toward this ambitious project from both funders and reviewers. In particular, the interdisciplinary nature of the project proved to pose serious challenges to evaluators. For example, reviewers from the European Research Council felt that a cell biologist should not run an ocean project. A foundation representative with no biology background argued that the biological data collected would be of little use simply because it was not linked to some recent earth-science databases. These issues reflect some of the major challenges faced by funding bodies when evaluating interdisciplinary proposals. It remains a difficult task for funders to find reviewers with the suitable set of expertise and a mindset appreciative of high-risk ideas. While there is a broad consensus that interdisciplinarity is a driver for innovation and discovery, efficient instruments to fund such projects are sorely lacking.Tara Oceans possible. Remarkably, the scientists involved in the project were so excited by the adventure that they were willing to contribute their own funding. A seemingly heteroclite number of bodies were approached: EMBL, the French Center for Atomic Energy (CEA), CNRS, the Council of Bretagne, the French Ministry of Research and all other institutions where consortium members were employed. Tara Expeditions furthermore negotiated private deals with various companies and organizations such as Foundation Veolia and agnès b. herself. All these manageable amounts turned out to be an efficient funding model that distributes the risk and burden among various partners, with little overhead, and is thus highly scalable. With this system, we eventually managed to secure funding for the expedition itself. Financial support for the analysis phase of the project and for the coordination of the large consortium was then partially covered by a more classical French funding program . The 3-year expedition itself (including boat maintenance and crew) costs about 6 million Euros and the sequencing, initial imaging and bioinformatics analysis about 10 million Euros . In the initial analysis phase that started in 2011  to ensure the highest scientific quality.In the end, it was only the collective enthusiasm and commitment of the individual participants that made et al, et al, et al, et al, et al, Tara Oceans expedition has had a wide public impact worldwide .“Journal de bord d'une scientifique”, S Nicaud .“Voyage autour du pôle à bord de Tara”, V Hilaire .“Plancton – aux origines du vivant” (Ulmer 2013), C Sardet.“Plankton – wonders of a drifting world” , C Sardet.Books:


In this paper the question of autonomy in delusional disorders is investigated using a phenomenological approach. I refer to the distinction between freedom of intentional action, and freedom of the will, and develop phenomenological descriptions of lived autonomy, taking into account the distinction between a pre-reflective and a reflective type. Drawing on a case report, I deliver finely-grained phenomenological descriptions of lived autonomy and experienced self-determination when acting on delusions. This analysis seeks to demonstrate that a person with delusions can be described as responsible for her behaviour on a ‘framed’ level , even though she is not autonomous on a higher (‘framing’) level (level of freedom of the will), if, and only if, the goods of agency for herself and others are respected. In these cases the person with delusions is very nearly comparable to people in love, who are also not free to choose their convictions, and who could also be rightly held responsible for the behaviour flowing from their convictions. Persons with delusions often claim to be autonomous if they are behaving in accordance with their delusional convictions. Can this claim be justified? In order to address this question I will develop fine-grained descriptions of experiences of autonomy, or of feeling free and self-determined, if acting on delusions from the first-person-perspective. However, investigating the experiential structure of being autonomous from the first-person-perspective faces a fundamental problem: employing methods that focus on the experiential structure from the first-person-perspective, like phenomenological methods, offer descriptions of the experiential structure, but not moral justifications. The phenomenological method, as applied in this paper, might therefore not appear well suited for this question. Nonetheless, it would be absurd if experiences of autonomy would not differ somehow from those experiences in which a person is, in spite of her own experience of feeling free and self-determined, not autonomous. Possible features of such a self-deception in delusions could be the impossibility of falsifying one’s convictions during ongoing delusions and the highly private character of delusional convictions not shared with one’s community. Hence the question remains: Is a person with delusions simply and generally deceived regarding a given experience of autonomy, if acting on delusions?In order to proceed, I first present a short phenomenological description of delusional convictions, mainly drawing on the German tradition of phenomenological psychopathology . In a subsequent  I provide a preliminary phenomenological description of lived autonomy, drawing on recently published work, and will then discuss lived autonomy in delusions more closely . In this Introduction section offer a detailed description of delusion-related alterations of lived autonomy, whether on the level of freedom of intentional action or of freedom of the will. Basically, I argue that freedom on the level of intentional action can be sufficient for profound autonomy, if the goods of agency are respected; and I attempt to demonstrate that persons with delusions are, in this respect, partially comparable – although with notable distinctions – to people in love. Lastly, in Limitations of lived autonomy in delusions section, I discuss this argument with respect to clinical aspects.Unkorrigierbarkeit (incorrigibility) of these convictions (ideas). The impossibility of the delusional content, which is often the most prominent feature in clinical settings, is only an accessory criterion for the psychopathological finding of delusional convictions. It merely indicates the private character of these convictions   I was unsure if I just imagined him or not. And I asked my guardian angels, and Michael, to walk in front of me and the others behind me. And it worked. He  stood at the staircase and looked up to me, all night. If he was truly a spirit, he must have seen the angels. And if I just imagined him, then I imagined him in adequate fashion”. This report demonstrates besides the gradual realness of her hallucinations, as is frequent in schizophrenia, and the delusional quality of her interpretations, the limit of her angels’ support. They did not chase or guide away the spirit of the dead man, nor did they render him harmless or convince Mrs. F. that he was harmless (for her) in a fundamental sense, or block her imagination . Instead, they protected her outwardly and in a more physical sense, as if they were some kind of supernatural body-guards.Nonetheless, the guardian angels offered help and relief from her point of view: “It is a connection of the heart. I feel it immediately, if he (Michael) stands behind me” . Thus, her delusional conviction was judged as a justified belief from her point of view, even though the veridicality of angels can neither be proven nor falsified on rational grounds . Sometimes, if I’m engaged with my grandson, it  is not even there. But that is only a distraction, it  is always there”. Obviously Mrs. F. could experience a flow-state of mind if being engaged with her grandson, even though she immediately devalued this freedom of action as ‘distraction’ if starting to reflect upon it. From her point of view she was convinced that the evil spirits were never banned, but only absent for a short moment. She reported that highly predictable, repetitive and, with the exception of her young grandson, socially isolated situations were best suited to provoke such ‘experiences of distraction’: “Sometimes I listen to audio books. I do that. That helps, carries me away. I slip out of my situation. I need happy ends. I have listened at least three times to it , there is nothing new in it anymore. That works! If something bad happens, I already know that it’s over soon. […] It’s only stories, a different world. That world is defined and fixed, I am acquainted with it, nothing can scare me anymore. That distracts me from this world – It is important to know what is about to come”. However, these strategies were not altogether reliable, especially during the night, as Mrs. F. reported.trema, or delusional mood, as described by Conrad  experiences as apparitions of spirits or angels was comforting insofar as it provided and offered a comprehensive explanation. Mrs. F. did not provide a precise description of the prodromal and early stages of her psychosis, usually avoiding these questions. Nonetheless, the delusional insight of archangel Michael’s givenness and protection came after a longer period of horrifying and perplexing experiences as described above, most probably involving a stage of  Conrad  which I will not discuss in this paper). Mrs. F. also faced such difficulty in her personal relationships as well as in her professional life. In this social niche she hid her psychotic experiences behind the culturally accepted topic of ‘esoteric phenomena’. In contrast to her own experience, the people calling her could believe her to be a medium or not, to have such apparitions or not. If she had, however, tried to convince her clients to the extent that she was convinced herself, they might call her ‘mad’ or ‘psychotic’. Obviously, interpersonal verification usually evaluates the deluded person’s point of view as ‘incorrect’, ‘non common-sensical’, ‘unusual’, ‘weird’, or even, psychopathologically correctly, as ‘delusional’. In other words, interpersonal support of one’s world- or self-view is seldom available [folie à deux[There is, furthermore, a missing effectivity in the social dimension. Despite their best efforts, persons with delusions are typically totally unable to convince others that their delusional convictions are true.  are no longer baffling, but accustomed, as well as repeatedly tested and approved. This also entails the perception of certain action-properties that correspond to one’s delusional insights and convictions on the one hand, and one’s experiential history and one’s  projects on the other . Insofar as one’s perceived action-properties and their pre-reflective valuing also mirror one’s former (and possibly accustomed) delusional experiences and one’s actions, behaviours or projects are answering these experiences. For example, Mrs. F. reacted automatically and nearly off-handedly when she met “Elizabeth”. She neither abreacted nor was perplexed or baffled, since such a meeting was not out of the ordinary. Or, as Mrs. F. commented: “You get used to everything”. Her life-world was constantly double-fold for over 2 decades, as she was well aware. Consequently she did not expect this “other world” to cease to exist, although some of these (psychotic) “other-world-experiences” were annoying or even horrifying. On the contrary, it would have been truly astonishing if such apparitions would not have taken place anymore. In other words: she did not simply actively develop a delusional explanation for the changes in her world and experience, but developed a victions  p. 108 aObviously, one’s delusional insights and convictions provide only superficial knowledge regarding the improvement of one’s situation, as Mrs. F.’ experiences demonstrate quite clearly. Her delusional insights as well as her profound acquaintance with psychotic experiences  did not really help her to change the givenness of the apparitions or other hallucinatory experiences and their delusional interpretation. This would, from a psychiatric vantage point, most probably support the regular use of a neuroleptic medication. She could, however, more easily cope with these hallucinations, being less startled and perplexed, and being able to distract herself actively from her otherwise constant awareness of “this other world”. These strategies were more or less habitualized and integrated in a highly structured daily routine, and supported her (relative) mental stability, helping her to feel at least partially “at home” in her life-world. Nonetheless, she recognized the limitations of her strategies and behavioural options. She located her impairments on the level of intentional action, but not on the level of free will: “It depends on how much strength you have, in order to come to term with things. That is important”. From a psychiatric perspective there is, however, a crucial and underlying impairment of free will, which is neither recognized nor reflectively attributed by Mrs. F. This refers primarily to the impossibility to de-select the delusional convictions and accept different and more reasonable, or common-sensical, explanations of her psychotic experiences, entailing different and possibly more effective strategies . Delusional convictions are obviously mixed blessings with respect to goals and strategies deriving from or depending on one’s delusional convictions, since they are usually neither achievable nor effective in a radical way. The “other world” was constantly the other side of her life-world, rendering her double-fold life-world both familiar and unhomelike at the same time.incorrigibility in Jaspers’ sense). Similarly, neither the difference between one’s  convictions, and the knowledge, interpretations or convictions of one’s peer group, nor the acknowledgement that knowledge is, in principal, falsifiable, provoke a critical review. Instead, delusional convictions are pre-reflectively valued by the deluded person as “true” [The missing effectivity to achieve goals with means founded on delusional convictions does not, contrary to what would be suspected, lead to a situation in which the deluded person reflectively re-frames these convictions  incorrigible convictions: The delusional person cannot help behaving in accordance with her delusional convictions. In this respect, she is not free. On the contrary, she is in the very nature of the case captivated by her delusionally interpreted and perceived objects and by her delusional convictions. Delusional convictions are, apparently, not a matter of choice . Follownecessary conditions for the possibility of rightly ordering the goods for agents. These goods of agency must, therefore, be effectively willed in the virtuous pursuit of the goods for an agent. Moreover, since one cannot think or reason rightly by oneself, that is, since one must think for oneself but cannot rightly think by oneself, these goods of agency must be effectively willed for others as well as for oneself” [The important question regarding the freedom of the deluded person’s will is therefore similar to the same question with respect to people in love: Is the deluded person at least free to set out some goals which do not directly accord with her delusional convictions? If she can, she will most surely have a double-orientation to reality  several members of her immediate family lived there already for several years and had invited her to move ; b) no other relative remained in her former vicinity; and c) her best friend had died half a year before and that she had no other relevant social contacts in her locale. She summarized in one session: “All that shows me  that my decision to have moved was as right as rain. That was obviously right”. As can be seen, the goods of agency of her loved ones and herself were respected in this decision at which she arrived after some months of intense consideration and discussions with her loved ones. Apparently delusional convictions or psychotic experiences did not directly influence this decision.A person with delusions is not free to choose her delusional convictions. Her responsibility for her behaviour ends, in principal, on the level of these delusional convictions; comparable, at least in an analogous sense, with a person who is not responsible for being in love with someone else. In both cases, however, responsibility can extend to the behaviour which flows from these convictions. In this respect the person with delusions is, at least conceptually, not different from her fellow citizens who have fallen in love. A person with delusions is interpersonally embedded just like every other human being. Apparently, if a person is interested in being a moral agent, whether she is deluded or in love, she also needs to be interested in reflectively judging whether her valuings adequately correspond to her interests, and whether her interests are best served by the way she behaves. Consequently, a person with delusions who is a morally responsible agent, or wants to be, is interested in intersubjective verifications of her own valuings, behavioural options and interests and hence interested in the goods of agency for herself and others. To re-iterate, this entails that a person can be described as responsible for her behaviour on a ‘framed’ level , even though she is not autonomous on a higher (‘framing’) level , if, and only if, the goods of agency for others and herself are truly (at least not arbitrary) respected. In these cases the person with delusions could be called autonomous.The inability to rectify one’s delusional convictions in reflection is, of course, not intentional. Various phenomenologically-informed psychiatrists have described this inability to reflectively reframe the delusional knowledge as a passively suffered inability ,24,32-35mechanische Registration”) or impaired in the sense of a monotonous disposition of experiences  both be reduced to the level of a mechanical registration schaft”, ,37; a thschaft”, ,38). Simschaft”,  argued tWahnlogik” (logic of delusions), as Ludwig Binswanger argued with respect to August Strindberg’s concept of “fate’s logic”, [doppelte Orientierung”; see Binswanger [To acknowledge that persons with delusions can be described as autonomous on the level of freedom of intentional action if, and only if, others are respected as  agents, does not say that persons with delusions necessarily act autonomously. Acting on delusions can of course lead to immoral behaviour, because a person with delusions is unable to deselect her delusional convictions, and because she is profoundly and pre-reflectively influenced by her delusional habituality. Moreover, persons with delusions could also intentionally and responsibly act immorally or illegally, even though they are neither acting on delusions nor rendered unable to grant goods of agency for others. If, however, she discloses her life-world mainly, or solely in the manner of a delusional workspace, which could be called a ‘paranoid atmosphere’, she cannot take the perspective of others adequately into account . Then th logic”, , p. 536 nswanger , p. 536 nswanger ). Mrs. Fnswanger . Living nswanger ,27,39,40To acknowledge that persons with delusions can behave self-determinedly, autonomously and responsibly does not deny (from a psychiatric point of view) that they are ill and could, or maybe even: should, be treated. They are, after all, most times at least partially “unhomelike” in their double-fold life-world, as were those of Mrs. F. This does not imply that deluded persons experience themselves as effective with respect to all aspects of their behaviour. They are usually unable to convince others about the trueness of their convictions. Furthermore, they are often ineffective in achieving goals and applying strategies directly deriving from, or relying upon, their delusional convictions. They are, however, typically able to achieve an explanation for the changes in their world. In this way, their freedom of intentional action is (in addition to symptom-related impairments of their free will) specifically altered. Persons with delusions are, as the case report of Mrs. F. most clearly demonstrated, able to experience themselves as free and self-determined in certain situations and actions; and they do in fact behave autonomously  when taking into account the goods of agency in the situations in which they are called upon to act adequately. This is not denying the possibility of intentionally acting immorally, although the others’ goods of agency are accepted in principal and could be granted adequately. As has been argued above, such an adequateness is even possible if acting on one’s delusions. Although this need not be the case, and might seldom be, it seems to be especially possible if this person maintains a double-orientation to reality, implying that she discloses her life-world in two ‘parallel’ or ‘each other alternately eclipsing’ manners of familiar workspaces.Therefore, our phenomenological investigation offers a possible answer to the question posed in this paper. Namely, yes, acting on delusions can indeed be autonomous, according to the person’s own experience of being free and self-determined, if the goods of agency are adequately respected not only for herself, but also for others. Persons with delusions are, in this respect, quite comparable to persons in love, who are also not free to choose their convictions, but can be held responsible for their behaviour flowing from their love. An important difference can be named in the simple fact that persons who have fallen in love tend to readily and deliberately grant others the goods of agency, especially those whom they love, while persons with delusions often have to struggle for maintaining goods of agency for others in their often double-fold familiar workspace. This seems to foster the difficulty to determine whether a person acting on delusions acted in fact autonomously, and was hence responsible for her behaviour, or not. Notably, not the manifest behaviour itself answers this question, but the adequateness of granted goods of agency for others in her familiar workspace, whether implied by virtues or integrated by explicit deliberation. Our phenomenological descriptions of lived autonomy in delusions, drawing on the classical and partial analogy between people in love and people with delusions, offer some clarifications regarding this most complex problem, but they remain descriptions nonetheless. The acknowledgement, however, that persons with delusions can behave autonomously, even if they act on their delusions, seem – at least to some extent – to be the grounds of a very traditional idea in psychiatry: that professionals should also try to be mediators between the different realities of their patients, even though this might sometimes not work.aMrs. F. is my patient treated regularly in the Outpatient Department of the Psychiatric University Hospital Charité at St Hedwig Hospital Berlin, Germany. She gave me informed consent to present her case and, specifically, to quote transcripts from some of our therapeutic sessions. “F.” is a pseudonym. Moreover, all patient information has been deindentified.The author declares that he has no competing interests.


Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use.To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns.Thirty-eight studies used five common definitions of risk attribution to glucocorticoid exposure: “current use”, “ever use”, “daily dose”, “cumulative dose” and “time variant”. One study attempted to combine multiple definitions where “cumulative dose” was nested within “daily dose”, covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for “time variant”, 1.07 to 2.8, and the largest for “cumulative dose”, ranging from risk estimates of 0.88 to 8.12.Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns. •A literature review on which methods are used to define risk attribution of glucocorticoid use to fractures was undertaken.•Five common methods of defining risk attribution of glucocorticoids were found.•No currently used method considers dose, duration and timing.•Dose, duration and timing are thought to affect the risk of fracture due to the dynamic patterns of glucocorticoid therapy. For both databases the years covered by the search were from the conception of the database until the end of October 2014.The search criteria used for inclusion of papers included terms for glucocorticoids, fractures, and RA, (see Appendix) and were the same for both databases. Searches were initially limited to English language, humans, adults with further limitations made to the publication type. In Medline, publication types removed included: case reports, Phase I or II clinical trials, reviews, meta analyses, duplicate publications, retracted publications and any other non-research article publications. In Embase, publication types removed included books, book series, conference papers, editorials, notes, reviews and short surveys. Following exclusions, abstracts were screened to ensure the topic of the paper was suitable and if no abstract was available within Ovid, attempts were made to find the paper online.3During a qualitative synthesis stage, a further 16 papers were excluded either because there was no analysis of effect of glucocorticoids on fracture reported (5 papers), only 1 fracture occurring in either the glucocorticoid exposed or unexposed cohorts (2 papers), no association between glucocorticoids and fracture was reported (5 papers), RA was not considered in the paper (2 papers) or if the English full text version was not available (2 papers).Thirty eight papers were selected for review . The def3.1Two definitions of glucocorticoid exposure were binary variables. Firstly the “current use” definition, which meant the participant was on glucocorticoids at the time of fracture and secondly the “ever use” definition, which attributed an incident fracture to glucocorticoid use if a participant had ever taken glucocorticoids during the study period. In the exposure pattern for a hypothetical patient shown in Of the 19 papers that reported results for “current use” of glucocorticoids, nine Within the 15 papers reporting “ever use” of glucocorticoids, six 3.2Two methods were used to attribute fractures to definitions of glucocorticoid exposure which demonstrated the effect of dose. Firstly the “daily dose” definition which described the dose the participant was on at the time of fracture and secondly the “cumulative dose” definition which described the total dose taken during the patients follow-up. In the hypothetical exposure pattern described in Of the 13 papers using “daily dose” of glucocorticoid, nine Of the eight papers reporting “cumulative dose”, four A plot of the differences within estimates of fracture risk from “daily dose” and “cumulative dose” are demonstrated in Two 3.3One commonly used definition described duration of glucocorticoid therapy, the “time variant” definition which described the change in risk of fracture by the length of time spent on glucocorticoids. In the hypothetical exposure pattern described in 3.4Of the three papers who reported other methods of defining glucocorticoid exposure, one No meta-analysis was attempted due to heterogeneity in the studies, such as the different fracture types, different comparator populations, study designs, different confounders, and small study numbers once stratified by risk attribution model.4Five common methods were identified within this literature review that defined risk attribution of fracture risk to oral glucocorticoids in patients with RA: “current use”, “ever use”, “daily dose”, “cumulative dose” and “time-variant”. A multi-variable model was also identified where “cumulative dose” was nested within “daily dose”. Whilst the majority of papers showed an increased risk of fracture, regardless of the method defining risk attribution, the magnitude of this risk varied greatly. For example, estimates of increased risk ranged from 1.03 per gram increase in cumulative dose The appropriateness of the analysis model is important to consider for drugs that are taken dynamically through time such as glucocorticoids see .The “current use” definition examines the association between the fracture and whether the patient was exposed to glucocorticoids on the day of the fracture, hence important assumptions for this model are that any prior glucocorticoid exposure does not affect the risk of fracture, and the dose of glucocorticoids on the day of fracture is not important. The wide range of results for “current use”, from 1.33 The “daily dose” definition assumes that the strength of the dose on the day of fracture has the largest effect on fracture risk however it typically does not consider historical doses. This method has an advantage in that it provides clinicians and patients with information about the extent to which increasing dose is likely to affect the risk of fracture. For example, de Nijs et al. The “cumulative dose” method assumes that all current and prior glucocorticoids have equal impact on fracture risk regardless of how recently they were taken. However, calculating cumulative dose can be difficult which may lead to misclassification and imprecision of estimates. The dynamic regeneration and repair of bone suggests cessation of glucocorticoids might be followed recovery in bone health as shown by Van Staa et al. The “time variant” method assumes that the duration spent on glucocorticoids affects fracture risk. Within this model, the majority of results found an increased fracture risk with increasing duration of use. However, the results are difficult to compare as they consider the unit of time as years Beyond the five models described above, and illustrated in None of the models described above considered dose, duration and timing simultaneously, despite it being probable that all are important. Furthermore, no study made a comparison of how recency of glucocorticoid exposure affects the risk of fractures. One novel method that does consider dose, duration, and timing is the weighted cumulative dose model Considering the limitations of this review, abstracts were screened and data extracted by a single reviewer. Only the two leading databases were included in the search for publications and papers not written in the English language were also excluded from the review. As the key focus of the publication was to identify the differences in methodology, this was felt to be reasonable. Within the publications, it was unclear whether the glucocorticoids were prescribed for RA or another illness. Despite a possible alternative indication within an RA population, any observed relationship would remain valid unless the effect of glucocorticoid therapy is modified significantly by the indication. Furthermore, this review spans the development of anti-TNF therapy for use in inflammatory conditions. Due to the potential direct impact of biologic therapy on fracture risk, a comparison between studies undertaken before and after 2000 would be useful. However, due to the heterogeneity of the study designs included within this review it is difficult to make a direct comparison within any given method between pre and post 2000 since there maybe unmeasured confounding.5There are five main methods by which fracture risk has been attributed to glucocorticoid exposure, none of which consider the dose, duration and timing of treatment. This means risk estimates will rarely consider the complex individual patterns of steroid treatment, and will thus not give an accurate fracture risk assessment for an individual patient. There are now opportunities with advanced analytical methods to incorporate all these factors into a single model, allowing the generation of risk estimates for any given pattern of steroid exposure.DER and WGD report no conflicts of interest. EMD has received speaker fees from Eli Lilly. CC has received consultancy fees and honoraria from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. TPvS reports grants on an observational research project from GSK and participation in expert meetings with GSK, Sanofi and Roche, all outside the submitted work.


The roles that neural oscillations play in the auditory cortex of the human brain are becoming clearer. Related research article Sedley W, Gander PE, Kumar S, Kovach CK, Oya H, Kawasaki H, Howard MA, Griffiths TD. 2016. Neural signatures of perceptual inference. eLife5:e11476. doi: 10.7554/eLife.11476Image Detailed analyses of electrical signals in the brain are telling us more about how we perceive soundsDo you like surprises? If you don’t, it might be because our nervous system works very hard to avoid being surprised. This often involves the nervous system trying to predict or “model” its own future as accurately as possible. For example, when we are listening to a string of sounds that appears to be unpredictable, such as a Charlie Parker-esque saxophone solo, our brain will still try to predict what the next note will be .Figure 1So-called generative models of sensory perception have put forward the idea that the nervous system relies on predictions instead of detailed information about each new sound or other sensory event . Under sPatterns of rhythmic activity in neurons known as neural oscillations are important to perception. These are exciting times for researchers working on neural oscillations because a framework that describes their specific contributions to perception is finally emerging. In short, the idea is that comparatively slow neural oscillations, known as “alpha” and “beta” oscillations, encode the predictions made by the nervous system. Therefore, alpha and beta oscillations do not communicate sensory information per se; rather, they modulate the sensory information that is relayed to the brain. Faster “gamma” oscillations, on the other hand, are thought to convey the degree of surprise triggered by a given sound.Now, in eLife, William Sedley and colleagues at Newcastle University and the University of Iowa report the results of work that sheds new light on the roles played by alpha, beta and gamma oscillations in the auditory cortex of the human brain . Three pSedley et al. surveyed the neural oscillations in the patients to extract three parameters associated with models of perception: prediction, precision and surprise . Their aTo date frameworks for predictive coding have been largely based on studies of the visual domain in non-human primates see . ResearcInterestingly, alpha oscillations have recently been tied to rhythmic changes in the degree to which a neuron boosts or reduces information about a sound . FittingSo what should we take from the work of Sedley et al.? The observed effects of prediction and surprise on neural activity are moderate at most; for example, surprise explained only very small portions of the changes in gamma oscillations in each patient. However, Sedley et al. restricted themselves to attractive, simple-to-interpret linear measures . Thus, these data probably provide a conservative estimate of how accurate populations of neurons in the auditory cortex encode prediction and surprise.The question still remains as to which aspects of neural communication we are missing by not being able to routinely record neural activity directly from the surface of the human brain. So we are surely in for more surprises, whether we like it or not.


Didelphis marsupialis) by riverine communities in an Amazon floodplain region.In the Amazon rainforest, biodiversity is a significant resource for traditional communities, as it can be used as a relevant source of protein and it has a promising zootherapeutic potential. Studies on knowledge and ways how local peoples use the fauna are still incipient. This paper presents both the knowledge on and food and medicinal uses of common opossum  per individual.The study showed that D. marsupialis is an important source of protein for riverine communities in the region studied. Its fat is used as a traditional medicine and it is indicated for many types of diseases. Although the species concerned is treated with hostility in various Brazilian regions, in the case of Abaetetuba this animal is strongly prized due to the good quality of its meat. However, despite the value assigned to the species, its consumption should be the subject of further studies, as this marsupial species has been described as a reservoir for parasites that cause severe diseases. The Amazon rainforest, which is among the largest biodiversity reserves in the world, plays an important role in the life of traditional communities, providing food, housing, transportation, household items, furniture, income, remedies, as well as other environmental services. Accordingly, the hunted fauna is crucial both as a protein and remedy source. Several studies conducted around the world have documented, through Ethnozoology, knowledge and ways how human populations use animal species –7. DespiDidelphis marsupialis Linnaeus, 1758 , a mammal with a wide geographical distribution in the Americas , often an adjective that characterizes the animal. For each ethnospecies cited, we asked respondents to speak about morphological features, habits, and places of occurrence. For this procedure, we followed the recommendations made by Berlin . As we did not collect any zoological material, we used the literature currently available on the subject, such as Guide to Mammals from the Neotropical Forest , as welly Berlin . Data weD. marsupialis, which corresponds to common opossum, Caluromys philander Linnaeus, 1758, Chironectes minimus , Metachirus nudicaudatus , and Philander opossum ; however, we do not know if cited species correspond to ethnospecies informed by respondents, as we did not collect animals for identification. In fact, we do not mean that there are only such ethnospecies, but we do claim that they are those best known by riverine people, and common opossum  is the most important due to its food and medicinal value. Therefore, our study is exclusively devoted to this species.Through the local ethnotaxonomy, respondents pointed out various types of opossum, which were distinguished considering their morphological features , habits, and places of occurrence. We registered 5 ethnospecies of opossum, classified by respondents this way: “mucura preta” [common opossum], “mucura branca” [white opossum], “mucura morganha” [“morganha” opossum], “mucura xixica” [“xixica” opossum], and “mucura do fundo” [bottom opossum]. The occurrence of these ethnospecies in the region was supported by the taxonomy provided in the literature , geograpmarsupium, used to carry offspring until they complete their development. Marsupials have nocturnal habits, they are usually solitary and provided with a defense mechanism that consists in expelling a fluid with a strong odor produced by a pair of perianal glands, which serves to ward off potential predators . During the hunting excursions, knowledge on the preferred environments of this animal greatly facilitates finding and capturing individuals when hunters rely on the use of dogs, which quickly identify a common opossum by sniffing.Indeed, some hunters reported that common opossum, when faced with a hunter, stands watching him, motionless, trying to recognize its predator. When excursions are nocturnal, they are dazzled by flashlights and start fighting with the hunter, trying to scare and expel him. According to reports by riverine people, the best times to hunt a common opossum are by the morning, when they are resting in burrows and there is better light; or at night, when individuals are in “vagrancy” or “mariscando” [pecking the ground]. Actors also said that between 8:00 p.m. and 02:00 a.m. is an excellent time to hunt.When the hunters have difficulties to obtain the game, a situation locally known as “panema”, they use various ways to reverse this failure state, such as, for instance, “bathing” the bandolier with chili pepper and then put it in a smokehouse. Many riverines reported us that pregnant women can cause “panema” if they eat bushmeat; in this case, there are a variety of bath recipes to drive misfortune away. Another practice taught was squeezing a lemon into the barrel and across the rifle, leaving it hanging down for two days at the pathway through which everyone passes, then the rifle must be washed in hot water. “Panema” is a state widely known among Amazon hunters, it is described in various anthropological and ethnoecological studies , 53–55.D. marsupialis is among the few current alternatives , deer [Mazama americana ], and common agouti . Respondent reports illustrate the importance of hunting for the local gastronomy: This meat is tenderer than beef. I think it is like the meat of common agouti, lowland paca, or deer. .I like it a lot. It has a different flavor, it is very soft. .The meat is very tasty. When restful, it becomes better. I mean by restful meat that the animal did not undergo stress. Meat was generally classified as having a very good flavor, when compared to other species, such as cattle, pig, and chicken. It was also characterized as very soft, it is similar to other bushmeats, such as lowland paca , is separated to produce the handmade medicinal oil. This medicine is produced by melting fat over a fire until it becomes oil. After this, a scent freshener is added to oil, to attenuate the strong smell, such as camphor, a substance extracted from the camphor tree  is low, hunting becomes an important income source. The price of a common opossum, which may be sold alive or already slaughtered, varies according to animal size and season of the year. It ranges from R$ 10.00  to R$ 40.00 , when the animal weighs about 5 kg; it is worth highlighting that live individuals are more expensive. On average, a common opossum weighs 2 kg and it costs R$ 30.00 . As wild animal trade is illegal in Brazil, as provided by Law 9,605/1989 [In fact, people sell this meat in their own community or in nearby areas, on demand or not. In the town fair, which is located on the left bank of Maratauíra River, a respondent told us that, whenever he hunts, even without any order, it is relatively easy to sell the product in the town fair, because this meat is highly demanded by residents due to its flavor, considered very good. A respondent explained us that when açaí palm extraction , therefore, they think the population remains stable. Given the diversity of discourses, we realize that all reports must be considered, since each member of the community has a particular way of addressing the environment. So, there is a need for conducting studies on population dynamics, in order to determine the demographic status of this species.Respondents’ concern about sustainability became clear when they reported to observe the species reproductive and growth periods, they claim to avoid hunting females with young. Another interesting discourse consists in observing the increased human population in the floodplain region and its consequent deforestation, something which led animals to get away from households. Thus, two respondents reported that opossums once came to the river bank and, nowadays, their sounds are no longer heard. This information reinforces the consequences of the relationship between community and environment: when deprived of their habitat, animals gradually move away from the households, avoiding a contact that could be harmful to their survival.If you bring everything you see, soon nothing else will be seen”. This comment was made by a community leader on predatory hunting, which has been the key factor to explain a possible decrease in the number of opossums, as he found out that many hunters do not observe any evidence of animal reproduction and hunt both males and females. The same respondent told us that some hunters are proud to hunt a large amount of animals, even over twenty opossums per hunting expedition. He has already found dead opossums in the woods, which perhaps were regarded as small and not relevant for trade. On this subject, another community member said that: “I think a person may hunt to sell a large amount of animals when he needs to do that for a living, but I do not agree with wastage, leaving bushmeat behind”. This reinforces the idea of community sustainable hunting: people should avoid hunting a large amount of animals and local species may not be endangered, regardless of their current conservation status [Another account was very important for understanding the relationship between human beings and nature in the community under study. A respondent said: “n status .According to an interviewee, in addition to the precautions taken, as already reported in this article, guidelines were acquired from governmental institutions about sustainable hunting practices, in order to safeguard opossum reproduction and keep its current population. This reflects what Coelho-de-Souza et al.  pointed D. marsupialis) constitutes a significant hunting resource for the local population, both from the food and medicinal viewpoint. In sporadic cases, it provides families with an additional income. The meat of this species is highly prized by residents, something which shows that hunting resources play an important role as a source of animal protein for traditional Amazon populations. Certainly, the pressure on D. marsupialis is due to shortage of other kinds of bushmeat in the region, as in upland forest areas, where there is a richer diversity of hunting fauna, people hardly eat opossum. We stress the importance of further research in the public health field, because some studies have pointed out the risks posed to human health by the consumption of marsupials contaminated with parasites.Studies on Ethnobiology and Ethnoecology are of great relevance because they register knowledge of local peoples on environment and natural resources. Such knowledge is key to promote dialogue and a closer contact between researchers and local actors , encoura


How did a South African end up in Australia via the Middle East, you might well ask? The story of this journey to becoming an “international” medical educator began in April 2005, when my cosy (but not mundane) routine at the University of KwaZulu-Natal (South Africa) was interrupted by an email inviting me to consider applying for a medical education post at the United Arab Emirates (UAE) University. Why would I want to work in the UAE or anywhere else, for that matter? Although being what I considered “well-travelled”, the thought of disrupting my relatively peaceful and comfortable existence in the city in which I was born, schooled and now worked, held little appeal.But, the seed had been sown.... After weighing up the pros and the cons, I took a huge leap of faith and applied for the position, not knowing what lay beyond the next four years or even if I would see out the four years in a new and strange country. My decision was certainly not taken lightly. In fact, it was a gestation of several months, particularly since I knew that if I resigned, considering the South African political landscape, it was unlikely that I would find a similar position on my return. So, leaving family, friends, assets and a lifestyle to which I was accustomed, I landed in Dubai in the height of summer (in excess of 45°C) and was transported to the garden city of Al Ain, in the middle of the Arabian desert. From a professional perspective, it was one of the best decisions I have made. The UAEU faculty comprised mostly expatriate academics and support staff with a wealth of knowledge and experience who too had had to make the often difficult decision to leave “home”, sometimes without their families, in search of, amongst other reasons, a different  experience, adventure, research opportunities, a tax-free income or perhaps exiled from their home country because of political strife. At the time of my arrival (June 2006), faculty originated from more than 25 countries. While many were from the region  or from North Africa , others hailed from more distant shores . Many of us lived in the same “compounds” and so became a close-knit family, sharing our stories of families left behind and caring for our inherited pets  who adopted us the minute we moved into our new accommodation. We regularly shared meals and frequently escaped to the desert or the coast to enjoy the splendour of outdoors, particularly in the cooler winter months. Colleagues soon became friends, often cemented by our common origins and the familiar “culture” of our heritage. Although continents now separate us, the bonds that united us when our paths crossed on foreign shores still remain, thanks largely to social media.Contract work away from home often comes with perks. The UAEU’s generous leave and research support, for example, allowed me to travel extensively both professionally and for leisure. I soon came to realise that Dubai and Abu Dhabi are the gateways to a significant part of the globe, with Africa, Europe and Asia readily accessible in a few hours. The UAE position was the springboard for developing a network of collaborators both locally and further afield. Either as a key note speaker at conferences or as an external examiner, I was able to travel to places I would never have dreamed of visiting had I stayed in South Africa: Indonesia, Syria, Saudi Arabia , Bahrain and Sudan. For well-earned vacations, I was able to explore the wonders of the Maldives, Sri Lanka, Bhutan, India, Jordan, Oman, Malta, Cyprus, Tanzania, Kenya and Zanzibar. Sadly, however, due to the “Arab Spring”, some places remain on my bucket list: Yemen, including Socotra and Algeria. Travelling on a South African passport, my little red automobile went into autopilot mode on the numerous Al Ain-Abu Dhabi trips to embassies and consulates. A bumper 30-page passport was needed as my standard 10-page  was soon full of expensive visas.Working abroad for the first time in a different culture and considering the soul-searching that had culminated in the decision to leave my homeland for an unknown future, sparked my curiosity. What drives individuals to work abroad, to become international medical educators? What are the issues that they face, particularly if the culture is far removed from their own? In collaboration with fellow international medical educators, some of whom I had yet to meet, we embarked on a study to explore what it really means to be an “international” educator. Starting with colleagues in the Middle East and then extending the study to capture an international audience, we advertised our survey through our global network of fellow educators. The inclusion criterion was simple: Are you or have you worked outside your home country as a medical educator? Our analysis of largely qualitative data is “work in progress”. I am, however, able report some of our preliminary findings. Eighty-nine individuals, representing 29 countries (7 continents), ranging in age from 28 to 82 (average: 51 years), 40% being female, responded. Eighty-four percent reported being medically qualified. English was the home language of just over 60% of the respondents, with the majority claiming to speak at least one other language. When asked which country they considered home, 30% identified the UK, with next largest group of respondents (15%) falling into “difficult to say” category, which included comments such as “I don’t feel attached to either country” or providing an answer with multiple countries. Of interest was the use of “now” by a number of respondents to indicate the country in which they were currently working as “home”, transcending the idea of “home” being the country of birth. From my personal experience, currently working in a second country since leaving South Africa, and having just submitted my Australian permanent residency application, “home” is beginning to blur.In 2006, Ron Harden described his vision of the future of medical education – transnational was the term he used. In such a scenario, the educators and students would be international and the curriculum would be “global”.