Background: Evidence-based guidelines published by health authorities for the promotion of health-enhancing physical activity (PA), continue to be implemented unsuccessfully and demonstrate a gap between evidence and policies. This review synthesizes evidence on factors influencing delivery, adoption and implementation of PA promotion guidelines within different policy sectors . Methods: Published literature was initially searched using PubMed, EBSCO, Google Scholar and continued through an iterative snowball technique. The literature review spanned the period 2002–2017. The realist synthesis approach was adopted to review the content of 39 included studies. An initial programme theory with a four-step chain from evidence emersion to implementation of guidelines was tested. Results: The synthesis furthers our understanding of the link between PA guidelines delivery and the actions of professionals responsible for implementation within health services, school departments and municipalities. The main mechanisms identified for guidance implementation were scientific legitimation, enforcement, feasibility, familiarity with concepts and PA habits. Threats emerged to the successful implementation of PA guidelines at national/local jurisdictional levels. Conclusions: The way PA guidelines are developed may influence their adoption by policy-makers and professionals. Useful lessons emerged that may inform synergies between policymaking and professional practices, promoting win-win multisectoral strategies. Worldwide trends of inactivity, which increase with economic development urge societies to invest in physical activity (PA) promotion to counteract the growing social and economic costs of multiple non-communicable diseases associated with insufficient PA levels . In lineStrong scientific evidence supports the relationship between built environment and trends toward physical (in)activity at population level ,8, despiTwo main types of guidelines for PA promotion have been produced. The first type encompasses official position statements or clinical and educational guidance documents underpinned by scientific evidence on the relationship between PA/exercise and health. Such guidelines consist of recommendations for reaching and maintaining health-enhancing levels of PA, targeting different age groups ,14, fromGuidelines are targeted to disseminate updated information and evidence-based recommendations in order to promote a change in behaviour toward a healthy lifestyle and adherence to recommended health-related practices. However, despite widespread circulation and publicity of clinical and educational health-related guidelines, they are often not applied ,22. A wiThe formulation of guidance to influence policymaking and professional practices is embedded in the broader process of knowledge translation . AccordiMultiple reasons explain why research findings and evidence-based guidance cannot be transferred in a simple linear way into policy ,31,32. TConcluding, an incomplete evidence base still exists to decide which guideline dissemination and implementation strategies may be effective; to this aim, a theoretical framework should drive the synthesis of evidence to enhance the adherence of different users . There iThe purpose of this realist review was to develop a conceptual framework of facilitators of and barriers to the delivery and adoption PA guidelines within different policy sectors. Specifically, we aimed to identify: (1) Mechanisms of advocacy through which PA entered onto the agenda setting and ways in which evidence was translated in PA guidelines; (2) Factors that may facilitate or hamper PA guidelines adoption within national plans or regulatory tools in different policy sectors and compliance by relevant practitioners. These issues were addressed using the realist synthesis approach , which iThe process from evidence emersion to the delivery of PA guidelines and to changing of regulatory tools and professional practices in multiple policy sectors was examined; thus conceptualising the guidance implementation process as a complex social intervention involving a complex implementation chain. Indeed, complex intervention programmes are by definition implemented by different stakeholders. Along the implementation chain, resources and opportunities are provided to and exploited by different decision makers. Based on this conceptualization, we used the “realist approach” of Ray Pawson  to revieTo map and articulate the key programme theories ,42 of PAThe general rationale of the initial programme theory is grounded on the evidence-based policy movement and on the key role attributed to guidelines as a tool to influence policymaking processes and, lastly, practitioners’ behaviour . SpecifiFor each step, possible realist explanations regarding mechanisms that underpin change in specific contexts were inferred from the reviewed literature by answering a number of specific sub-questions. To generate and prioritize the review sub-questions, we conducted a consensus process utilising the content expertise of policy makers and scholars of PA promotion. To this aim, a sheet was sent to four targeted experts from the Health-Enhancing PA (HEPA) Europe network working at national/European level to obtain suggestions about the consistency of the initial programme theory and judgments about the relevance of the related questions. The sheet included a set of questions centred on the promotion of PA for health. HEPA experts’ feedback underlined the need to monitor, at European and national level, the effectiveness of PA guidelines implementation.The sub-questions for each step were mainly expressed in terms of possible hypotheses to test Context-Mechanism-Outcome configurations. In a realist review, a Context-Mechanism-Outcome pattern configuration allows to retrace regularities and to understand “what works for whom in which circumstances” . For exaPrimary studies, reviews and evaluation studies were initially searched through PubMed, EBSCO, Google Scholar and, according to the realist synthesis approach, continued through the snowball technique with continuous iterative search. Policy documents were mainly retrieved from European Union, European Commission, WHO and WHO Europe websites. The search strategy involved intersections of the following terms: physical activity; physical inactivity; health-enhancing physical activity; physical exercise; active commuting; guideline; guidance; guidance implementation; guidance dissemination; health promotion guidance; plan; knowledge translation; built environment; evaluation; agenda setting; advocacy; delivery, adoption; implementation; multisectoral intervention(s); multisectoral strategy/-ies; policy; healthy environment; school; education; sport; transport; community; partnership; local authority.It is important to underline that for realist synthesis in general and for our review questions in particular, relevant data sources go beyond traditional disciplinary and sector boundaries. Seven hundred and seventy-six electronic references were collected considering all relevant research designs and methods; 535 references covering publication years 2002 to 2017 (date last searched: August 2017) were analysed. A first selection was performed excluding those publications not specifically addressing evidence emersion, building, delivery or dissemination of PA guidance. In a subsequent selection step, references were included according to their pertinence to the four propositions and specific sub-questions. At the end of the process, we selected 39 studies, among them seven systematic reviews, in order to respond to the sub-questions related to each step of the initial programme theory testing. The selection strategy is represented in The inclusion of data to inform programme theory development was guided by the RAMESES principles of relevance and rigour . The quaThe typical Context-Mechanism-Outcome realist configuration was adopted to compare and interrogate literature and synthesise evidence. According to the scope of this review, we attempted to identify recurrent patterns of contexts and outcomes, giving priority to the following contexts: (1) main policy sectors , (2) different governmental levels , (3) country areas with a special focus on the EU context. Successively, we sought to explain these recurrent patterns or demi-regularities through the mechanisms by which they occurred. All the assumptions, corresponding to each of the four steps of the initial programme theory, were tested through comparison with literature search results. How and Through which Mechanism of Advocacy did PA enter onto the Agenda Setting? For this first step concerning how clinical and epidemiological evidence influences policymaking processes and how it mobilises interest groups for PA, we chose to focus on the case of EU compared with the United States and Australia. The focus on Europe, contrasted with other main developed economies with analogous inactivity epidemics, was prompted by the actual interest of the European Union institutions for multisectoral PA promotion strategies ,10,11. TOur findings indicate that the current EU attention to obesity and physically (in)activity in strategic documents  depends The risk inherent in linking PA promotion mainly to obesity prevention and reduction is that to neglect evidence on the far broader role played by PA in health enhancement and maintenance independently of weight loss and, vice versa, by physical inactivity in the development of major non-communicable diseases . FurtherAre PA guidelines developed synthesising data meaningful for different policy sectors?Is there coherence among PA guidelines delivered by different authorities?Guidance delivered by public health authorities having scientific legitimation, plays a relevant role in orienting policymaking processes toward PA promotion . NeverthDifferences in PA guidelines among regional health departments of the same country sometimes emerged as regards purposes, evidence, focus of prescriptions and optimal amount of exercise . In 2006Are PA guidelines coherently integrated within national/regional plans for PA, physical education at school and sports promotion?Which are the determinants of effective PA guidelines adoption in the health sector at local government level?Is the perception of PA as a policy priority influenced by policy sectors different from health ?Did medical schools adopt curricula coherently with PA guidelines?The WHO Europe  highlighIn the sport sector, elite sport facilities and events are often prioritised at the expense of those for recreational sport-for-all based on the erroneous assumption that such prioritisation would increase general participation in sport. Indeed in Europe, there is a paucity of evidence supporting the hypothesis that “Sport for All” and elite sport benefit each other  and thatState funding for PA, adequate staffing and supportive state legislature seem relevant to the adoption of PA guidelines in the health sector . A mechaGuidelines dissemination seems to translate into increased adoption and implementation by state level practitioners more clearly and consistently than by local level practitioners. In The Netherlands, local government is required by national law to develop health policy at the municipal level. Nevertheless, local health policy did not appear to be of pivotal importance to the operations or organization of stakeholders mainly due to the dominance of a medical approach to health that slows the progress of integrated health policies . In NorwIn the United States, urban planners seem to play a more relevant role in PA promotion as compared to local health departments, being able to anticipate innovative, multisectoral win-win strategies for active lifestyle and commuting . A publiFinally, the so-called “Cinderella” status of PA in health care and public health  seems reDo school principals’ beliefs about compatibility of PA and academic achievement matter? Do medical doctors’ attitudes influence PA prescription? Do urban planners’ and administrators’ attitudes influence PA promotion interventions?School principals who have a supportive attitude to students walking to school seem more likely to believe that active travel benefits not only the health of students, but also their scholastic success . Thus, aLack of time to promote PA is the most often cited perceived barrier ,91,92,93The perception of “feasibility” by public officers and administrators of multisectoral policy guidelines seems a relevant mechanism to increase the potential of successful policy implementation to promote an environment more conducive to PA among children . FurtherEvidence-based PA guidelines delivered by international health bodies play a significant role for the dissemination of PA recommendations and the realization of multisectoral strategies for PA promotion. However, there is not a simple direct relationship between scientific evidence, delivery of guidance, adoption of policy measures to contrast physical inactivity trends and changes in professional practices. The general purpose of the present realist review was to develop a conceptual framework of facilitators of and barriers to the delivery and adoption PA guidelines within different policy sectors. We analysed the long chain leading from advocacy to adoption of PA guidelines and, specifically, (1) the mechanisms of advocacy and the ways of evidence translation into PA guidelines; (2) the factors that may facilitate or hamper PA guidelines adoption in different policy sectors and the compliance by relevant practitioners. Expected and unexpected outcomes are explained by a plurality of mechanisms triggered at each step of this complex implementation chain .Several barriers hamper PA guidelines delivery and adoption. They range from factors that limit the meaningfulness of evidence and the subsequent translation into coherent and useful recommendations for different target groups  to weak mechanisms of advocacy for PA promotion. The main weaknesses identified regarding the delivery and adoption of PA guidelines were : (a) PA A critical point of evidence-based guidelines is that a medical approach dominates “how” evidence is built and data gathering is fulfilled. It implies some limitations in research agendas about PA, involvement of relevant sectors of knowledge, evidence search techniques, evaluation methods and source of evidence narrowed to health-related databases. According to some scholars, broad conceptual and methodological gaps need to be addressed to progress research on public open space and PA and therefore to better design PA guidelines . When inThreats to the adoption of PA guidelines within national or local strategic plans and regulatory measures emerged. A key problem is that while the health sector, mainly at national or international level, usually provides leadership or stewardship for PA and publishes guidelines; it then also needs to engage other sectors in the quest for promoting PA. Indeed, the action on PA often falls in the domain of professionals belonging to other sectors such as education, sport urban planning and transport . Non-synPA guidelines seem more effective for urban planning and transport sectors if framed in broader terms  and inspired by a holistic view of health that encompasses other dominant concerns as quality of life and environmental sustainability. Effective PA promotion strategies can be implemented by coordinators of the built environment and assisted by academics with research expertise in architecture, planning and health . EffectiResults demonstrated that the adoption of, or adherence to PA guidelines are influenced by factors acting at different community and individual levels: previous experiences of effective PA promotion interventions in the community, competition among different priorities or other health promotion guidelines , as wellMany mechanisms mediate the long journey that goes from evidence emersion to PA promotion guidelines delivery and adoption by several sectors. Some of the mechanisms were not present in the initial programme theory, but emerged along the review. Though the role of scientific knowledge is widely recognised, the adoption of PA guidance varies and the goals are reframed according to each policy sector, its priorities and dominant organisational culture. For example, school principals and their beliefs about the compatibility of physical education with academic performance represents a key issue, while for urban planners at municipal level, active commuting and cycling are stronger priorities than PA “per se”. In the sport sector, PA policy competes with policies that prioritise investments for elite sport facilities and events. In conclusion, policy sectors other than health seem to play a pivotal role for ensuring effectiveness of health-enhancing PA promotion. Thus, it seems necessary to extract evidence and offer recommendations that are meaningful for other sectors.To our knowledge, this review represents the first attempt to employ the realist synthesis approach to analyse the delivery and adoption of PA promotion guidelines more broadly in several policy sectors. It may complement review outcomes focused on the uptake of clinical guidelines in the health sector obtained with a realist synthesis approach .However, in each policy sector, the concepts of “evidence” and “evidence-based policy” differ in terms of quality assessment and the relevance of evidence in specific circumstances . The preIn the present review, the realist synthesis approach was used to investigate variability in the adoption of PA guidelines in different circumstances, namely at different levels of governance and in different policy sectors ,101,102.As evidence and guidance delivery alone are not sufficient to influence practitioners and policy maker behaviours ,36,75, tOur conclusion is that PA guidance delivery should go beyond a narrow focus on the “know-do gap” , acknowl


Uganda, with an estimated population of 35 million people, is a landlocked country that forms part of the East African Union member states. The country is divided into nine political regions , in whic1 Being one of only two countries where incidence was on the rise in 2013, HIV remains a major public health problem in Uganda.2 HIV prevalence varies across the country, being highest in the Central region and near urban centres and lowest in the mid-eastern and West Nile regions.Uganda is classified as a high burden HIV country with an estimated 1.6 million people living with HIV/AIDS and 140 000 new cases reported annually .1 Being 3 to 500 cells/mm3.3 Uganda was one of the first countries to adopt these recommendations and began implementing the revised treatment guidelines in April 2014.4 Under the revised antiretroviral therapy guidelines, CD4 enumeration remains critical to staging the need for antiretroviral therapy among HIV-positive patients aged 15 years and above.5 In addition, the World Health Organization recommended the use of viral load testing as the preferred antiretroviral therapy monitoring approach. The Ministry of Health in Uganda subsequently adopted viral load monitoring for antiretroviral therapy patients into the national guidelines. Uganda’s viral load programme has since scaled up rapidly, but universal access has not yet been achieved. For patients who do not have access to viral load services, CD4 testing remains essential for monitoring antiretroviral therapy response. As Uganda scales up the new World Health Organization/UNAIDS 90-90-90 strategy,6 there has been a steep rise in the number of people in need of HIV testing and viral load monitoring across the country. It is estimated that over 850 000 people will be on antiretroviral therapy by the end of 2016. Meeting these targets will require innovative ways of developing laboratory systems, including scaling up of point-of-care (POC) tests for HIV testing, diagnosis of opportunistic infections and monitoring response to treatment or disease progression.In 2013, the World Health Organization changed the recommendation for initiation of antiretroviral therapy from a CD4 count of 350 cells/mm9The laboratory network in Uganda consists of a five-tiered system covering the following levels: national, regional, general hospital (district), health centre IV and health centre III. Laboratories at national, regional and district levels are relatively well developed, whereas laboratories at lower health centre IV and III level generally have inadequate space, no running water, frequent power interruptions and inadequate working space. In order to overcome some of these challenges, the country has established a national sample and results referral network based on hubs. A hub is a high volume laboratory that functions as a referral laboratory for 30–40 lower level laboratories. Complex tests that cannot be handled at the hub, such as early infant diagnosis (EID), viral load testing, culture for tuberculosis and outbreak investigation samples, among others, are centralised at the Central Public Health Laboratory (CPHL) and other reference laboratories.®, BD FACSCount®, Partec CyFlow® Counter and Alere Pima™ for CD4 counts, and ELISA and rapid diagnostics tests for HIV. In addition, BD MGIT is used for tuberculosis cultures and Cepheid GeneXpert® for PCR. POC tests are deployed in remote rural areas or where test volumes are low, while conventional analysers are used mainly at hubs and in urban areas.Although testing capacity has been increased through deployment of modern high-throughput equipment, national testing targets for EID and viral load have not yet been met. It can be argued that lack of, or limited access to, laboratory services may be overcome through centralisation of testing services and building of new laboratories. However, this course of action requires substantial investment and could result in a significant delay. Moreover, there is a nagging fear that if donor funding is significantly reduced or entirely stopped, such projects may be rendered ‘white elephants’. Cognisant of such possibilities, over the last few years, Uganda has adopted a combination of conventional testing platforms at higher level health facilities and POC testing at lower level health facilities. Thus, in Uganda, EID and viral load testing use Roche Molecular Diagnostics and Abbott Molecular laboratory methods, while CD4 and HIV testing use a mix of conventional analysers and POC devices, including BD FACSCaliburThe quality assurance programme in Uganda is still in its infancy. Like many African countries, Uganda has adopted the Strengthening Laboratory Management Towards Accreditation and Stepwise Laboratory Quality Improvement Process Towards Accreditation approaches to improving quality systems in laboratories. However, the supporting components to this programme, such as internal quality control procedures and external quality assessment (EQA), are quite weak. Although CPHL has put in place some measures in collaboration with the Uganda Virus Research Institute, the National Tuberculosis and Leprosy Control Program, the Infectious Diseases Institute and the National Drug Authority to carry out some EQA functions, major gaps still exist. There is poor EQA coverage, particularly for POC testing; low response rates from participating facilities and lack of a comprehensive corrective action plans to support poorly performing laboratories. Only panels for HIV testing and tuberculosis smear microscopy are produced locally, whereas panels for clinical chemistry, haematology, bacteriology, CD4 counts and viral load are supplied by external agencies. The EQA schemes and suppliers are not centrally coordinated. Because Uganda anticipates a rapid scale up of POC testing, CPHL has developed plans to review the POC quality assurance policies and framework.Uganda has a National Health Laboratory Policy and Strategic Plan that guides the implementation of Laboratory Quality Management systems across the health laboratory services. However, the strategies do not explicitly address POC testing deployment or POC testing quality issues. Therefore, there is a need to review the National Laboratory Policy and Strategic Plan so as to address quality systems for POC testing.A functional EQA scheme consists of six key components , specifiIn Uganda, implementation of the EQA scheme will be done in three phases, as outlined below.Planning and developing an HIV-related POC quality system requires the review of the current guidelines and standards, and therefore requires the engagement of relevant leaders to execute the activities. With leadership engagement, establishment of the national quality assurance coordination team is easier and the roles and responsibilities of the selected teams can be defined . Before The implementation strategy for quality assurance of POC testing requires quality assurance training and certification. This will further involve activities such as the process control, audits, site support supervision and mentorship, all of which constitute the fundamental components of capacity building. Establishment of EQA  production, packaging/shipping through hubs, programme management and outsourcing will be implemented when the need arises . The quaFor the sustainability of the quality assurance programme planning, allocation of resources and continuous encouragement of socio-economic entrepreneurship are required. Sustainability implementation will require focused monitoring and evaluation initiatives, country ownership and involvement, a high level of advocacy, and mobilisation of the community. Feedback, corrective action and inter-lab comparisons are vital for quality assurance programmes, as these are the basis for improvement.Estimating the cost of EQA activities will include understanding the country’s needs based on identified interventions to inform key policy decisions and reducing high costs. External support will be sought to price the final model of service provision and to establish a cost-effective POC testing EQA scheme that is integrated in a comprehensive National EQA Program. In cases where it will be necessary to produce EQA panels locally, the activity will be undertaken by the Uganda National Health Laboratory and respective reference laboratories. EQA materials will be distributed using the hub system. Technical assistance and other resources will be mobilised both internally and externally to support the programme.Uganda is actively working to implement a robust quality assurance programme that will address POC testing in the country. Although the quality assurance programme is still in its infancy, Uganda has already adopted Strengthening Laboratory Management Towards Accreditation and Stepwise Laboratory Quality Improvement Process Towards Accreditation to improve overall laboratory quality systems and is focusing on how to improve internal quality control procedures and EQA.Uganda has always taken great strides to meet challenges with innovative approaches. The country established a national sample and results referral network based on hubs to improve EID services, which also resulted in cost savings for the programme and in turn improved other health services. More recently, Uganda performed a rapid assessment of the POC testing quality assurance policy and framework to identify major gaps that should be addressed.Uganda understands the strength of working in a collaborative manner with all institutions to implement a sustainable country-owned EQA programme. CPHL is working with the Uganda Virus Research Institute, the National Tuberculosis and Leprosy Control Program, the Infectious Diseases Institute and the National Drug Authority to plan and carry out EQA functions necessary to support quality CD4, EID, and viral load services.


Background: Training in innovation and entrepreneurship (I&E) in medical education has become increasingly prevalent among medical schools to train students in complex problem solving and solution design.Objective: We aim to characterize I&E education in US allopathic medical schools to provide insight into the features and objectives of this growing field.Design: I&E programs were identified in 2016 via structured searches of 158 US allopathic medical school websites. Program characteristics were identified from public program resources and structured phone interviews with program directors. Curricular themes were identified via thematic analysis of program resources, and themes referenced by >50% of programs were analyzed.Results: Thirteen programs were identified. Programs had a median age of four years, and contained a median of 13 students. Programs were led by faculty from diverse professional backgrounds, and all awarded formal recognition to graduates. Nine programs spanned all four years of medical school and ten programs required a capstone project. Thematic analysis revealed seven educational themes  and two teaching method themes  referenced by >50% of programs.Conclusions: The landscape of medical school I&E programs is rapidly expanding to address newfound skills needed by physicians due to ongoing changes in healthcare, but programs remain relatively few and small compared to class size. This landscape analysis is the first review of I&E in medical education and may contribute to development of a formal educational framework or competency model for current or future programs.Abbreviations: AAMC: American Association of Medical Colleges; AMA: American Medical Association; I&E: Innovation and entrepreneurship In a rapidly changing healthcare system, students entering US medical schools today have educational needs and goals unmet by the current medical education system . The onginnovation and entrepreneurship (I&E). Historically, I&E has been taught in undergraduate courses focused on business or product development, but is now a common field of study in graduate business, engineering, and design programs  leadership styles, change management, conflict resolution, inter-professional team dynamics, [and] use of organizational management tools’ [t tools’ .Technology : The understanding of technology was defined across programs as the ability to adeptly use and develop medical products, devices, and/or digital technologies. Programs consistently suggested that understanding of technology is necessary for the translation of potential solutions into clinical application. Example skills listed as related to this educational theme include interdisciplinary collaboration [boration , productboration , needs iboration , and proboration .Healthcare systems : The understanding of healthcare systems was defined as the ability to understand the various interactions between stakeholders in healthcare. There were varying definitions of a healthcare system, ranging from individual community health systems to the entire US healthcare system [e system ,21. Howee system  and syste system .Business of medicine : Working knowledge of finance and reimbursement was cited by several programs as a valuable skillset. There was a wide range of applications of this educational theme, including a general understanding of financial reimbursement [ursement , the appursement , and theursement .Enhanced adaptability : The need for enhanced adaptability was mentioned in the context of preparing future physicians for a changing healthcare system. Specifically, programs sought to prepare students for changes in the technological, financial, and regulatory environment [ironment ,28. The Active learning : All programs included elements of active learning, helping students practice the skills-based components of innovation. Active learning manifested in the form of group workshops, prototyping sessions, hackathons, field trips to innovative companies, M4 capstone projects, internships, and immersion experiences.Interdisciplinary teaching : Nearly all programs taught their students in interdisciplinary settings. Programs incorporated students and faculty from medical, engineering, science, business, and/or law backgrounds, and identified interdisciplinary collaboration as essential to healthcare innovation, particularly in the translation of medical technologies into effective clinical solutions.Our mixed methods study of US allopathic medical schools identifies a small but rapidly growing presence of I&E programs in medical education. These programs are advancing student readiness for today’s complex healthcare environment by covering novel educational themes with active, interdisciplinary pedagogy.These programs were comprised of student subsets representing less than 15% of a given medical school class, were led by several core faculty members from diverse career backgrounds, and awarded graduating students with at least one form of formal recognition. Programs varied with respect to structure, though the majority spanned greater than one year and required completion of a capstone project.Thematic analysis revealed that programs addressed many of the same competencies and employed similar teaching methods. The majority of programs taught concepts pertaining to innovation and its application in entrepreneurship, leadership, technology, healthcare systems, and the business of medicine. Programs cited that cultivation of these competencies will provide enhanced adaptability within a changing healthcare landscape. Programs helped students hone these competencies through active learning techniques, including workshops, prototyping sessions, and capstone projects. Experiences also tended to be interdisciplinary, in that students and faculty were typically from diverse educational and professional backgrounds. Though these categories provide a sense of general curricular goals, none of the programs publicly proposed a formal competency model. In addition, the results show a lack of consensus regarding the specific skill sets required to reach competency within the educational themes. This lack of connection to skills is best illustrated in the themes of healthcare systems and enhanced adaptability.NUvention: Medical [Health, Technology and Engineering Program launched StemSurgical Inc., a medical device company that designs high throughput bone marrow harvesting tools [Interestingly, our study revealed two exciting examples of program graduates applying their I&E education beyond the classroom. In 2012, four Northwestern graduate students launched a medical device company, Briteseed, which markets a surgical device the students invented while participating in  Medical . Likewisng tools .We also identified a number of novel education initiatives which have otherwise not been noted in other areas of medical education. As an example, the field of design thinking, a problem solving methodology that utilizes user-centric strategies such as ideation and rapid prototyping to solve complex problems, has found its way into a growing number of I&E programs ,23,26,29The study had several limitations. To the best of our knowledge, no resource has previously compiled a list of medical school I&E programs, and thus we relied upon our described search techniques and insight from other program directors to avoid omitting eligible programs. Therefore, it is possible that additional programs exist at allopathic medical schools that were missed by our search methods. In addition, we limited our analysis to allopathic medical schools, so our findings cannot be extrapolated to I&E programs that may exist at osteopathic medical schools. Our definition of I&E programs also excluded individual courses or more informal offerings, which likely represent another important facet of I&E education. Finally, our thematic analysis relied on publicly accessible information, and it is possible that many programs have changed curricula or policies since publishing this information.We hope to increase transparency and collaboration among the cited programs, and to provide educators at medical schools lacking I&E programs the foundational resources to launch similar programs at their own institutions. Additionally, although all programs cited in our study have descriptions available online, prospective medical students currently lack an efficient means by which to learn which medical schools offer I&E programs. We aim to empower prospective medical students interested in I&E with insight into this emerging educational niche.The landscape of I&E programs among US allopathic medical schools is rapidly expanding to address the newfound needs placed on physicians by recent and ongoing changes within healthcare. Considering that these programs aim to address aspects of medicine that all physicians will encounter, we propose further study of I&E education and how it may eventually integrate into the core medical school curriculum. Efforts to increase transparency and collaboration among existing I&E programs should promote the optimization and expansion required to eventually enable the widespread integration of I&E into medical education.


Editorial on the Research TopicEyeblink Classical Conditioning in Psychiatric Conditions: Novel Uses for a Classic ParadigmAs one of the most basic forms of associative learning, eyeblink conditioning (EBC) is a model paradigm with unique utility in the assessment of complex behavioral disorders, including psychiatric disorders. Two major EBC paradigms utilized with human subjects are delay EBC [in which a conditioned stimulus  co-terminates with an unconditioned stimulus ] and trace EBC . The neural substrates of EBC in these paradigms are well delineated and include the cerebellum and anterior interpositus nucleus, the hippocampus, and prefrontal cortex. Variability in acquisition, discrimination, timing, sensitization, and/or extinction of classically conditioned eyeblink responses provides insight into the behavioral and neurobiological characteristics of a variety of psychiatric and neurological disorders.Kent et al. review the existing literature on EBC studies in schizophrenia, perhaps the most studied psychiatric diagnostic group with respect to EBC to date. In their review of 15 studies, they report that decreased percent CRs (impaired learning) is the most robust and replicated finding in this population, with equivocal findings associated with CR timing. Importantly, differences between schizophrenic and healthy controls in percent CRs appear to be reflective of cerebellar abnormalities—supported by neuroimaging data and data from first-degree relatives—rather than confounding issues such as medication use. However, the authors highlight the importance of methodological consistency across EBC paradigms for accurate interpretation and synthesis of data across studies, an issue critical in the evaluation of any behavioral measure. Bolbecker et al. report data on delay EBC in schizophrenia using an analytic approach—hierarchical liner modeling—that has the advantages of less restrictive assumptions and inclusion of unequal variances in comparison to more traditionally employed analytic approaches, such as repeated measures analysis of variance. The authors did not find differences between schizophrenic patients and age-matched healthy controls in learning rate, but did observe group differences in time to maximal learning level and plateau of learning response, with schizophrenic patients exhibiting saturation in learning earlier and at a lower level in comparison to healthy controls.In this Research Topic, Cheng et al. provide summaries of both animal and human work describing the impact of alcohol use disorders in adults and fetal alcohol syndrome in children. EBC studies in these populations have illuminated structural and functional differences in both the mature and developing cerebellum, as well as learning differences in these diagnostic groups when compared to healthy controls.Weiss and Disterhoft emphasize the utility of rabbit EBC for assessing cerebro-cerebellar functional connectivity. The role of hippocampus, fronto-temporal and cerebellar cortices, and of cerebellar deep nuclei has been well characterized in a wide variety of normal states as well as dysfunctional psychiatric conditions. Their review concentrates on models of schizophrenia and Alzheimer’s dementia, but also points out applications for normal aging, Parkinson’s disease, progressive supranuclear palsy, alcoholism, and post-traumatic stress disorder (PTSD). Indeed, the rabbit EBC model was developed in parallel with assessment of human EBC in a series of studies from the laboratories of Gormezano, his students, and colleagues, which have allowed mechanistic, physiological, and pharmacological assessments to be carried out in depth.Schreurs and Burhans detail development of a preclinical EBC extinction model with potential utility for treatment of inappropriate conditioned behaviors and hyperarousal in individuals suffering from PTSD, whether combat veterans or approximately 5–25% of the general populace who experience severe anxiety, sleeplessness, hypervigilance, and/or flashbacks after trauma constitute a group at extreme risk for suicide. Their exposure paradigm uses conditioning-specific reflex modification and attenuated intensity US presentations to enhance the likely clinical utility for human applications.Janke et al. discuss dysregulation of brain-derived neurotrophic factor (BDNF) in anxiety disorders, including impaired behavioral inhibition temperament (BI). They describe facilitated delay EBC in both human and animal subjects exhibiting BI. In their animal model after EBC, increases in mRNA for hippocampal BDNF were observed in both the dentate gyrus and CA3 regions, along with upregulation of TrkB receptors and downstream activity-related cytoskeletal protein (Arc) in the hippocampus, but these increases were blunted in the strain showing faster acquisition and hyper-sensitivity to both CS and US. Hippocampal BDNF administration reversed the behavioral sensitization, suggesting treatment strategies that enhance that hippocampal BDNF may be effective for a variety of anxiety disorders.Welsh and Oristaglio provide a secondary analysis of children with autism spectrum disorder (ASD) who underwent both delay and trace EBC. They grouped children based on their diagnosis into either an autistic disorder group or an Asperger’s syndrome or Pervasive Developmental Disorder (Asp/PDD) group. Neither ASD group showed differences in CR acquisition compared to an age- and IQ-matched group of typically developing (TD) children. However, the groups differed with respect to CR timing alterations, with the Asp/PDD group showing delayed CR onset and peak latencies during trace conditioning that were not observed in the ASD or TD groups. These data may illustrate differences in the underlying biology of these two diagnostic groups that are expressed as behavioral differences. Although the authors indicate that these differences must be further tested in a larger trial, these data are representative of the types of approaches that are supported by the NIMH’s Research Domain Criterion (RDoc) initiative that aims to use a variety of approaches, including behavioral phenotyping, to help our field better distinguish brain dysfunction among patients with psychiatric illnesses.Parker describes the potential for timing tasks to aid in our understanding of cognitive impairment across diagnostic groups, again in line with the RDoC approach. She asserts that tasks that involve temporal processing, such as EBC, can reflect connectivity between the cerebellum and frontal cortex, and in particular, hypothesizes that the medial frontal cortex plays a critical role in cognitive processing that occurs in timing tasks. This reciprocal relationship between cerebellar and frontal cortical regions is an important area of further investigation.Similarly, Cicchese and Berry also focus on timing and the critical role of theta  in many forms of learning and memory. They review non-theta contingent EBC, demonstrating its importance as a model system for characterizing neurobiological dysfunction in severe cognitive disorders, including schizophrenia, major depression, and Alzheimer’s disease. From their animal studies and an extensive review of the human literature, they argue that theta rhythms serve to coordinate timing and synchrony of activity in widely distributed brain systems critical for acquiring, consolidating, and retrieving memories, both for complex cognitive sequences and for relatively low-level tasks such as classical EBC.The studies in this Research Topic highlight the utility of EBC in assessing the integrity of cerebellar and medial temporal lobe function in both normal and pathological states and support wider uses of this behavioral paradigm across a multitude of psychiatric disorders. The editors’ earlier work on impaired trace EBC in depressed individuals  illustraAll authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The DOE BioEnergy Science Center has operated as a virtual center with multiple partners for a decade targeting overcoming biomass recalcitrance. BESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion to improve bioenergy processes and markets. This article provides an overview of key accomplishments in overcoming recalcitrance via better plants, better microbes, and better tools and combinations. A perspective on the aspects of successful center operation is presented. Overbiofuels .” Due tobiofuels , Oak RidRecalcitrance began as an operationally defined phenotype. With both applied and fundamental goals, BESC perceived that we needed to transform the understanding of recalcitrance; this required detailed knowledge of the chemical, structural, and physical properties of biomass and how these properties influenced deconstruction by enzymes and thermophilic microorganisms. This search led to altering plant cell wall properties by manipulating key plant polymer biosynthetic pathways, which led to studies of the interactions of the plant cell walls and the enzymes and microbes during deconstruction and fermentation. The BESC team has redefined recalcitrance so that now recalcitrance is on the path to being an understandable and manipulatable set of properties based on cell wall formation and bioconversion. A key outcome of the BESC team’s approach was to transform understanding in both fundamental and operational impacts to strategies that will eliminate recalcitrance as an economic barrier to commercialization.This singular focus on recalcitrance science was BESC’s hallmark worldwide. BESC was organized into three areas: Biomass Formation and Modification, Biomass Deconstruction and Conversion, and Enabling Technologies Fig. . All thrFrom late 2007 to fall 2017, BESC published more than 945 journal articles, 10% in high-profile journals (impact factor > 9) and advanced the education of more than 230 professionals, who are now productive members of the bioeconomy workforce. More details with respect to the output of BESC and the other two USDOE Bioenergy Research Centers are in Slater et al. [Populus and switchgrass (Panicum virgatum) were the chosen feedstocks for studies of cell wall-related genetic modifications that could impact recalcitrance and inform understanding. Both are high yield perennials recognized as potential domestic biofeedstocks [Significant advances were made in understanding, manipulating, and managing plant cell wall recalcitrance and conversion. We showed that multiple plant genes control cell wall recalcitrance, and that manipulation of these genes can yield lower recalcitrance perennial biofeedstocks . This inPopulus. This included both high-throughput (HTP) recalcitrance phenotyping and sequencing along with other omics for these natural variants (as well as the generated transgenics). These resulted in advances in genome-wide association studies (GWAS) [BESC led large-scale campaigns to understand natural variation in both switchgrass and s (GWAS) –28.Populus and switchgrass lines with reduced recalcitrance arising from both directed transgenics and natural variants. We utilized a collective “TOP Line” experimental design protocol [BESC conducted greenhouse and field trials for a limited number of protocol  with mulprotocol , 30–32.One goal of BESC was to understand the molecular basis of recalcitrance. The reduced recalcitrance feedstock biomass generated in BESC was analyzed by a series of chemical, biochemical, molecular, and systems biology approaches. The outcome was the identification of multiple wall polymers whose modified abundance or structure could be engineered to reduce feedstock recalcitrance . The resFrom this research, we can see a path for improving feedstocks by cisgenic manipulations, by selecting the best natural variants, or by genetically assisted breeding .edstocks , 6. Popuedstocks . SwitchgClostridium thermocellum and Caldicellulosiruptor bescii), and (b) conferring to yeasts the ability to ferment cellulose by virtue of heterologous expression of glycosyl hydrolases. We came to regard the former approach as more promising and by the end of BESC were focused exclusively on this path. Key conversion advances led by BESC included:C. thermocellum achieved the highest carbohydrate solubilization yields which were several-fold higher yields than industry-standard fungal cellulase [Large differences were found among the biocatalysts in the most comprehensive comparative evaluation to date of biomass deconstruction under controlled conditions. Among the biocatalysts tested, thermophilic anaerobes and specifically ellulase –37.C. thermocellum and Caldicellulosiruptor spp., and use of these tools to initiate metabolic engineering of these non-model microbes [We developed and improved the genetic tools for thermophiles, most notably microbes –41.C. thermocellum. Thermoanaerobacter saccharolyticum was improved to produce economically recoverable ethanol concentrations at near-theoretical yield in the hemicellulose-fermenting [C. thermocellum at unprecedented yields and titers [C. thermocellum by elimination of side-products [Substantial advances were made in understanding and manipulating the metabolism of target CBP microbes. Zhou et al. , describrmenting . Iso-butd titers . Ethanolproducts –47.Caldicellulosiruptor species and C. thermocellum [C. bescii, was shown to be a particularly powerful hydrolytic enzyme despite being inhibited by the presence of lignin [BESC identified the specific deconstruction enzymes which target the major biopolymers of lignocellulosic biomass. Work on enzyme fundamentals emphasized multifunctional cellulases based on the enzymes found in mocellum . CelA, af lignin , 50.C. thermocellum is capable of active fermentation in the presence of mechanical milling—an approach referred to as co-treatment [C. thermocellum was able to achieve greater than 85% carbohydrate solubilization for Populus and switchgrass in the absence of added enzymes and thermochemical pretreatment implying that C. thermocellum can attack all the major chemical linkages in representative woody and herbaceous lignocellulose crops given sufficient physical access.BESC demonstrated that reatment , 51, 52.One-step Consolidated Bioprocessing (CBP) without added enzymes  was the The development of high-throughput methods for rapid analysis of pretreatment and enzymatic hydrolysis allowed for rapid identification of low recalcitrant plant lines from thousands of natural and transgenic variants. These low recalcitrant plant lines then could be characterized using multiple analytical and omic approaches which rapidly advanced BESC’s deeper understanding of the recalcitrance phenotype –55.Increased understanding of recalcitrance was supported by developing techniques such as glycome profiling , and impBESC also supported the development of new ways to image the chemical components comprising the cell wall. Raman spectroscopy was used to image hemicellulose for the first time . ModifieCo-solvent enhanced lignocellulosic fractionation was developed as a new pretreatment that removes significant amounts of lignin and increases enzymatic digestibility of biomass .Populus [The center was able to provide integrated omics data for key processes. Integrated omics of microbial growth on complex lignocellulosic biomass over time provided a detailed view of the molecular machinery (metabolites and enzymes) and revealed temporal adaptation to a complex, lignocellulose substrate . ProfiliPopulus .Lignin has been shown to play a key role in biomass recalcitrance –69. The Enabling technologies were organized to develop and apply cutting-edge analytical methodologies to characterize biomass as well as its conversion. There was also significant omics and computational biology of the modified plants and microbes to help improve metabolic models. The resulting data were used to create new insights into how biomass structure and chemistry affect recalcitrance during CBP or pretreatment. These efforts included analyses of partially digested solid residues from CBP.As a thematically rather than institutionally defined center, BESC recognized early on the need to develop a shared organizing vision, a sense of priority, and strong mechanisms for shared samples and data as well as strong management. This structure allowed us to recruit many of the nation’s experts in recalcitrance and to draw on the intellectual cultures and strengths of different institutions. BESC successfully implemented a flexible management approach, modeled after successful biotech startup companies that have relied on academic research to strengthen their science base and industrial partnerships to translate discoveries into commercial products.Over the decade, BESC established a distinctive, high functioning collaborative team with participants from 22 institutions and a broad range of disciplines. As needs and research progressed, six partners left the center and five new partners joined. BESC included researchers from universities, national laboratories, and private companies. These partners included major efforts at ORNL, University of Georgia, Athens, and the National Renewable Energy Laboratory. Specialized expertise was provided by Dartmouth College, Georgia Tech, University of Tennessee, Knoxville, Cornell University, West Virginia University, University of California-Riverside, University of California-Los Angeles, North Carolina State University, University of North Texas along with The Samuel Roberts Noble Foundation (Noble). Earlier partners included Brookhaven National Laboratory, University of Minnesota, Washington State University, and Virginia Polytechnic Institute. Our industrial partners included DuPont, Mascoma Corporation, Diversa Corporation, ArborGen, Inc., Ceres, Inc., and GreenWood Resources, Inc.BESC brought together individuals, institutions, and disciplines to focus on understanding and ameliorating biomass recalcitrance. As a result of discussions at our retreats and other fora, ideas emerged that would not have happened without a center so designed. As a result of common management, resources, and non-disclosure agreements, barriers to collaboration were substantially lowered as compared to individual investigators acting on their own. Students and postdoctoral staff were among the greatest beneficiaries. Upon hiring BESC-supported students, companies observed that they had extraordinary experience functioning as part of interdisciplinary teams. As an indication of the extent of collaboration, about half of our publications in year 9 had co-authors from more than one BESC institution.Top-down structures and bottom-up networking were useful and complementary in fostering integration. Weekly calls were held by the science and operational management team. Twice-monthly calls were held with a larger group (roughly 15) consisting of the science management and activity leads, with topics alternating between science and management calls. BESC refreshed its management, all but two of the original eight management team members being replaced by year 10; this included hiring a new Director. Keeping leadership fresh was also accomplished as early and mid-career staff—some of them graduate students at the start of BESC—were promoted and given added responsibility such that by the end of BESC they comprised over half of BESC activity and project leads. Task- and organism-specific points of contact were designated to facilitate interactions among teams and individuals.Technology transfer, managed by a Commercialization Council chaired by ORNL, and consisting of the COO and technology transfer leads from each partner institution operated as a community of best practice to strategically and effectively engage with industrial partners. A “storefront” on the BESC website provided a centralized online portal for industry to view available technologies for licensing and partnering. The IP management plan was built on a common Inter-Institutional Agreement template that allows a designated lead institution to offer jointly owned IP from multiple BESC members . AnotherPopulus trichocarpa [Tech transfer metrics at the time of writing featured more than 190 invention disclosures resulting in 60 patent applications and 21 executed licenses. For example, in 2016, two companies licensed a gene discovered using GWAS in chocarpa . GreenWohttp://www.thermo.com), which was specifically designed to manage flexible laboratory processes. This system has an Oracle relational database engine as its back end and generated numerous customized workflows and web interfaces to view results from laboratory processes and experimental campaigns, which has successfully been used to track more than 100,000 samples during the BESC project.The ability to freely share materials and protect potential IP that belong to the BESC partners is an essential function for expeditious collaboration within the Center. A laboratory information management system (LIMS) served as the main mechanism for documenting the transfer of materials among BESC partners as allowed under the innovative BESC Master Material Transfer Agreement. The LIMS also represented the primary system for tracking large experimental campaigns, protocols, data, and metadata and for data quality assurance. LIMS is a relatively mature system developed during BESC using a commercial LIMS software package, Nautilus (http://www.learnbiofuels.org) with information and downloadable biofuels-related lesson plans has received more than 45,000 page views. A Biofuels/Alternative Energy iPad software app “Road Trip Challenge” is available through the iTunes App Store with eight “trips” between hub museums. Importantly, the program is moving closer to becoming self-sustaining. Of the over 50,000 students, teachers, and parents reached during 2016, 81% were served with no direct program-support cost to BESC.The nationwide BESC Outreach program targeted science enrichment and educational standards in 4th–6th grades. In collaboration with the Creative Discovery Museum in Chattanooga, Tennessee, we developed a hub-and-spoke model using hubs at 18 national museums and science centers in 14 states  . The “FaBESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion , 77 to i


The process of creating healthy weight standards consisted of identifying needs and priorities, developing and harmonizing standards, testing the exchange of data messages, and demonstrating use-cases. Healthy weight products include 2 message standards, 5 use-cases, 31 LOINC  question codes, 7 healthy weight value sets, 15 public–private engagements with health information technology implementers, and 2 technical guides. A logic model and action steps outline activities toward better data capture, interoperable systems, and information use. Sharing experiences and leveraging this work in the context of broader priorities can inform the development of electronic information standards for similar core conditions and guide strategic activities in electronic systems.Electronic information technology standards facilitate high-quality, uniform collection of data for improved delivery and measurement of health care services. Electronic information standards also aid information exchange between secure systems that link health care and public health for better coordination of patient care and better-informed population health improvement activities. We developed international data standards for healthy weight that provide common definitions for electronic information technology. The standards capture healthy weight data on the “ABCDs” of a visit to a health care provider that addresses initial obesity prevention and care:  The overall age-adjusted prevalence of obesity among US adults aged 20 years or older in 2013–2014 was approximately 38%  can suppClinical document architecture (CDA): a standard developed by Health Level 7 International (HL7) that defines the data structure and semantics  of clinical documents, such as discharge summaries and progress notes, to facilitate better electronic data exchange.Data element: a unit of data defined (such as by character length or type) for processing; multiple elements are combined into a patient record or document.Electronic health information (EHI): information in a digital format that is captured or transferred by computerized tools such as electronic health records (EHRs), personal health records, personal wellness devices, health information exchanges, registries, and population health databases.Electronic health record (EHR): a computerized collection of patient and population health information that is stored in a digital format and maintained by health professionals and official agencies. Electronic information standards: specifications established by a standardizing organization that define and enhance electronic information management by describing structure, encoding, and meaning. Examples are message content and interoperability requirements.Harmonization: adjustment of differences and inconsistencies among items, such as specifications, methods, or systems, to make them aligned, uniform, or mutually compatible across organizations or entities.Healthy Weight message: a communication, such as a collection of content or codes such as those defined for the Healthy Weight standard, that is sent electronically from one IT tool to another in an exchange of electronic information; the sender and receiver of this information must both be similar, or built to the same standard, in order for the interaction to be successful.Profile: a document developed by Integrating Healthcare Enterprise International (IHE) that provides a common language for purchasers, vendors, and developers and defines precisely how standards  can be implemented to meet certain clinical needs.Healthy Weight standards: specifications related to healthy weight that enhance electronic information management.Healthy Weight visit: a health care provider visit that addresses the first steps of obesity prevention and management in a stepwise approach to care as well as chronic disease prevention; this initial health promotion and planning could be applicable to the overall patient population .Information technology (IT) implementer: a person who puts a system into practice. In this article on Healthy Weight standards, implementers fulfill or build the electronic system to specifications so they can send or receive healthy weight messages.Interoperability: the ability to securely and seamlessly exchange, interpret, and use information among permitted information systems.Interoperability standard: specifications that enable data to be shared among those with permissions  regardless of the application or application vendor.Logical observation identifiers names and codes (LOINC): a database of standardized codes for medical observations.Message standard: specifications that define the content  and structure of a message.Object identifier: a globally unambiguous, unique, persistent name assigned to something in computing, such as the unique number given to the value sets housed in the PHIN VADS .Observational result (ORU): a Health Level Seven International (HL7) message standard that provides structured patient-oriented data on clinical observations.Use-case scenario: a sequence of event steps depicting how data can meaningfully flow and be used by people  across systems.Standard: a specification that is an established norm or requirement that describes how to define, structure, and organize data or information.Systematized Nomenclature of Medicine (SNOMED): a standardized vocabulary of clinical terminology that is used by physicians and other health care providers for the electronic exchange of clinical health information.Value set: a group of codes used to define clinical concepts.interoperability, are useful for coordinating patient care, reporting data to public health agencies, and conducting population health analytics .Key steps in the process of developing the Healthy Weight standards were the following: identifying needs and priorities for electronic information standards; developing and aligning standards for data content and interoperability; testing and demonstrating data transmission; and deploying the standards . These aClinicians identified the need for improvements in obesity-related data in the EHR, and public health practitioners communicated the need for electronic information standards . AdditioThe development of Healthy Weight standards advanced through 2 independent organizations. The first organization, Health Level Seven International (HL7), is devoted to the development of interoperability standards for EHI exchange, integration, sharing, and retrieval. We defined data message content in partnership with domain experts from the American Academy of Pediatrics; technical experts from Lantana Consulting Group; members of CDC’s Healthy Weight Expert Panel, which consisted of clinical and health care management experts; state and local partners who participated in CDC’s Healthy Weight webinar; and additional content and surveillance experts. We accepted, documented, and integrated input from October 2010 through September 2013. Members of the HL7 Public Health and Emergency Response Committee wrote the implementation guide for the Healthy Weight standards. An approval process took place before publication that included a public comment period, a comment resolution involving the HL7 Public Health and Emergency Response Committee and the party who suggested the changes, and incorporation of agreed-upon revisions.The second organization, Integrating the Healthcare Enterprise International (IHE), is a public–private global initiative supported by end users worldwide to improve patient care by harmonizing the exchange of health care information. Standards were developed through a similar process to that of HL7, including input from CDC’s expert panel, webinar participants, additional experts, and public comment. The IHE Quality Research and Public Health Committee wrote a case profile  that specified both message content and interoperability requirements; the case profile defined actors  in 5 data-flow transactions used to capture Healthy Weight data and communicate these data to public health information systems. The development of complementary standards by 2 organizations independently was intended to increase interoperability and maximize use of Healthy Weight data by information systems.www.regenstrief.org) to create new LOINC  data elements that could be used in health management. Additionally, we created Healthy Weight value sets  in conjunction with the HL7 and IHE development processes. The Healthy Weight value sets are housed in the Public Health Information Network Vocabulary Access and Distribution System  and protocols    from exiAlignment activities took place through a collaborative development process. Alignment promotes interoperability, which optimizes integration of similar data and maximizes use of health care information by health care providers, practitioners, advocates, and payers. Webinars hosted by CDC for state and local partners throughout the development process allowed input from leaders in EHI-based surveillance and others who planned to use the data. Federal subject matter experts provided input on topic areas such as obesity, nutrition, physical activity, and surveillance. Also, professional organizations co-led or contributed to the development of the Healthy Weight standards to ensure that the standards would meet the needs of their members. Health information system vendors engaged in this project provided expertise on integration solutions and existing technical frameworks ,31. Addiwww.ihe.net/Connectathon/; www.himssconference.org/; http://phiconference.org/). Implementers tested whether Healthy Weight messages could be exchanged between entities. After EHI systems passed testing, implementers demonstrated use-case scenarios at interoperability showcases (forums where implementers exhibit their capabilities with the purpose of spurring adoption).After creating the Healthy Weight standards, we began a testing and demonstration process to stimulate development, awareness, and dissemination. Implementers built EHI systems to adhere to the specifications defined in the Healthy Weight profile and then introduced these EHI products at several international conferences t Report , which dentation , which dAn IT implementer demonstrated at interoperability showcases how EHRs can capture and track high-quality Healthy Weight information at the pediatric well-child visit to inform care, accurately document the child’s growth trajectory, and improve practice quality. This information, along with other information on routine care , were securely communicated as a message to health registries, which then could send parsed information to permitted health care providers and public health groups that support patient-level and community-level health activities. Other implementers demonstrated a scenario in which an adult was seen for a weight-management visit. The “ABCDs” of Healthy Weight were available in the EHR for health care providers, thus delivering information for decisions, facilitating efficient workflow, and improving documentation. EHRs exchanged data with personal devices and health records, a waiting-room kiosk, and specialist referrals, thus providing objective data and improving care coordination. Once EHI data from multiple patients were combined and assessed, this scenario illustrated how analyzed information could be used to help prioritize a worksite intervention to strengthen the community’s obesity management efforts.http://wiki.siframework.org/Structured+Data+Capture+Initiative) present an opportunity for Healthy Weight standards to align with developing architectures for precise collection of data elements in EHRs. Also, Healthy Weight standards should continue to be updated with feedback from implementers and best practices as the science advances.IT data standards for the Healthy Weight measure are published and available for use by all stakeholders. Common metrics and coordination across strategies could be leveraged for an intervention framework that broadens capacity, combines commitments, streamlines efforts, and unites on common measures of high-impact, high-burden health issues. Enhancements of Healthy Weight standards continue via the refinement and maintenance process. Continued harmonization through comparative analyses to relevant Healthy Weight and EHR-based efforts will identify gaps, overlaps, and recommendations for changes. In particular, advancements in the Structured Data Capture Initiative , intermediate term, and long term (within 10 years) to increasingly benefit individuals and communities. The ultimate goal of cross-stakeholder engagement in coordinated, strategic action is to advance the health and well-being of the population through improved prevention and management. Activities are intended to improve outcomes related to each measure of the Healthy Weight standard content. Thus, coordinated actions lead to improved BMI, behaviors, and health care satisfaction; empowered patients active in self-management; and resilient communities designed for wellness.Healthy Weight activities fit within and support broader international strategic directions for obesity, IT, surveillance, and health care and public health linkages. The intervention framework of obesity prevention and management spans key behaviors  and settings  . HealthyHealthy weight is a priority health concern among patients, health care providers, and communities, and addressing its magnitude calls for coordinated prevention and management efforts. Now that the Healthy Weight standards have been developed, aligned, and tested, they are ready for use. Collaborative multi-stakeholder activities that use health IT and leverage standards across systems have the potential to improve information systems and accelerate positive outcomes. In the patient–provider interaction, capturing and fully using standardized Healthy Weight data may transform the delivery and coordination of care, increase the quality of and satisfaction with obesity-related care, decrease costs, and improve health outcomes. At the public health or system level, accessing and maximizing Healthy Weight data may fill gaps in surveillance and population-level analytics, inform evaluations and interventions, and ensure improvements to build healthy communities. Prioritizing action steps and synergistic efforts across stakeholders may catalyze achievement of positive outcomes and thus advance global health and well-being.


Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement. The discovery of microbes dates back to the 1700s. Historically, Antonie van Leeuwenhoek peered and examined dental plaque sampled from himself and others through his microscope. His sense of awe and his early appreciation of the diversity our microbial partners were evident. He named the microbes “Dierken”, meaning small lively objects  is the first curated description of a human-associated microbiome and provides tools for use in understanding the role of the microbiome in health and disease. The purpose of HOMD is to provide the scientific community with comprehensive information on the approximately 700 prokaryote species that are present in the human oral cavity. HOMD is based on a curated 16S rRNA gene-based provisional naming scheme. Over the past 20 years, the laboratory has sequenced over 600 16S RNA gene libraries and obtained over 35,000 clone sequences. The samples came from healthy subjects and subjects with over a dozen disease states such as caries, periodontal disease, endodontic infections and oral cancer. The HOMD links sequence data with phenotypic, phylogenetic, clinical and bibliographic information. The organization, integration and presentation of the HOMD data can use as a model for microbiome data from other human body sites such as gut, skin, vagina  subgingival plaque. The study also revealed relationship among microbial community membership and function. Furthermore, they indicated the variation of microbial carriage between subjects down to the species and strain level, and variation of carriage of microbial taxa while metabolic pathways remained stable within a healthy population  was established with the mission of generating research resources enabling comprehensive characterization of the human microbiota and analysis of their role in human health and disease at the end of 2007  and constitute a potential risk factor for certain systemic diseases , generalized chronic periodontitis (n = 25), peri-implantitis (n = 14), localized aggressive periodontitis (n = 8), to sequenced 16S rRNA genes in 10 selected species. They finally found the red complex bacteria were the most prevalent with very high levels in all groups. Fusobacterium nucleatum (F. nucleatum)was detected in all samples at high levels. The green and blue complex bacteria were less prevalent compared with red and orange complex, except Aggregatibacter actinomycetemcomitas was detected in all localized aggressive periodontitis groups , oral lichen planus (OLP) and systemic lupus erythematosus (SLE) are common diseases of oral mucosa or specific manifestation of systematic diseases in oral mucosa, which draw a lot of attention of the public. OLK is defined as a white oral lesion not related to another disease process and the lesion is largely asymptomatic  than in the HC (0.34%) groups which demonstrated OLK might be associated with changes in the salivary microbiota  and healthy controls (n = 32), Amer et al. obtained increased abundance of Fusobacteria and reduced levels of Firmicutes in patients with OLK. Moreover, severe dysplasia was associated with elevated levels of Leptotrichia spp. and Campylobacter concisus , and the data showed Lichen planus is a common chronic mucocutaneous inflammatory. The prevalence of OLP ranges from 0.1%–4% in the general population , and amplified the V4 region of 16S rRNA gene from subgingival dental plaque DNA extracts. Compositions of oral microbiota in SLE individuals were different , peri-implant mucositis (n = 8) and peri-implantitis (n = 6) sites and compared the data, which revealed that Eubacterium minutum was correlated with Prevotella intermedia in peri-implantitis sites, suggesting the association of Eubacterium with peri-implantitis. These findings indicated that periodontal pathogens might be closely related to peri-implantitis  is one of the earliest to be found. Nowadays, there’re more convincing evidences for correlations between liver cirrhosis, gastrointestinal cancers and oral microbiomes.Inflammatory bowel disease (IBD) includes a spectrum of diseases from ulcerative colitis (UC) to Crohn’s disease (CD)  mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner, unraveling a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease  is a typical example.AD is the most common example of dementia causing around 60%–80% of all cases, characterized by cognitive deficit and has a complex, multifactorial etiology  and obesity have been proved to be associated with oral microbiomes.Diabetes mellitus is characterized by hyperglycemia, inflammation and high oxidative stress, which can lead to systemic complications. There is a bidirectional relationship between periodontal disease and diabetes. Microbiome plays a key role in homeostasis and affects several pathologic processes, including diabetes  have been found to be associated with oral microbiome changes. Madianos et al.,  found thObesity has also been found to be associated with oral microbiome. As the inflammatory nature of obesity is widely recognized, Goodson et al. found composition of salivary bacteria changes in overweight women. Bacterial species could serve as biological indicators of developing overweight condition. Oral bacteria may participate in the pathology that leads to obesity  is a common female endocrine condition of unclear etiology characterized by hyperandrogenism, amenorrhoea and polycystic ovarian morphology, often complicated by infertility, obesity, insulin resistance and low-grade inflammation. The gut microbiome is known to contribute to several of these conditions. Recently, an association between stool and saliva microbiome community profiles was shown , and make difference on multi-system diseases performances in immune system, such as human immunodeficiency virus (HIV) infection.RA is an autoimmune disorder, associated with increased mortality owing to cardiovascular and other systemic complications. However, etiology of RA remains elusive. Although studies on genetic predisposition to RA have implicated genes such as HLA-DRB1, TNFAIP3, PTPN22 and PADI4, environmental factors have also been shown to contribute to disease pathogenesis (McInnes and Schett, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all 3 sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. It suggests potential for using microbiome composition for prognosis and diagnosis.Microbial triggers have been implicated in RA (Zhang et al., Veillonella, Prevotella, Megasphaera and Campylobacter species than in healthy controls (Dang et al., HIV infection is associated with a range of oral conditions, and increased numbers of disease-associated microbial species have previously been found in HIV-positive subjects. Elevated viremia in untreated patients is associated with significantly higher proportions of potentially pathogenic These evidences suggest that there is a shift in the oral microbiome and these changes might be associated with HIV infection and/or HIV-treatment and other oral manifestations associated with disease (Heron and Elahi, Correlations between cardiovascular system diseases aren’t strong enough for now, but researchers did proved some potential connections between atherosclerosis and oral microbiomes.Chryseomonas, Veillonella and Streptococcus in the majority of atherosclerotic patients’ oral mocrobiomes (Koren et al., Atherosclerosis is characterized by accumulation of cholesterol and recruitment of macrophages to the arterial wall. It can thus be considered both a metabolic and an inflammatory disease Hansson, . By 16S The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Interaction and balance of a variety of oral microorganisms help human body against invasion of the undesirable stimulation outside. However, imbalance of microbial flora contributes to oral and whole-body systematic diseases. Oral microbiomes play an important role in human microbial community and human health status. Studies in oral microbiomes and their interactions with whole-body microbiomes in variable body sites and variable health condition are critical in our cognition of human body and how to make effect on human health improvement.


Traditionally, clinical decision making has been perceived as a purely rational and cognitive process. Recently, a number of authors have linked emotional intelligence (EI) to clinical decision making (CDM) and calls have been made for an increased focus on EI skills for clinicians. The objective of this integrative literature review was to identify and synthesise the empirical evidence for a role of emotion in CDM.A systematic search of the bibliographic databases PubMed, PsychINFO, and CINAHL (EBSCO) was conducted to identify empirical studies of clinician populations. Search terms were focused to identify studies reporting clinician emotion OR clinician emotional intelligence OR emotional competence AND clinical decision making OR clinical reasoning.Twenty three papers were retained for synthesis. These represented empirical work from qualitative, quantitative, and mixed-methods approaches and comprised work with a focus on experienced emotion and on skills associated with emotional intelligence. The studies examined nurses (10), physicians (7), occupational therapists (1), physiotherapists (1), mixed clinician samples (3), and unspecified infectious disease experts (1). We identified two main themes in the context of clinical decision making: the subjective experience of emotion; and, the application of emotion and cognition in CDM. Sub-themes under the subjective experience of emotion were: emotional response to contextual pressures; emotional responses to others; and, intentional exclusion of emotion from CDM. Under the application of emotion and cognition in CDM, sub-themes were: compassionate emotional labour – responsiveness to patient emotion within CDM; interdisciplinary tension regarding the significance and meaning of emotion in CDM; and, emotion and moral judgement.Clinicians’ experienced emotions can and do affect clinical decision making, although acknowledgement of that is far from universal. Importantly, this occurs in the in the absence of a clear theoretical framework and educational preparation may not reflect the importance of emotional competence to effective CDM.The online version of this article (10.1186/s12909-017-1089-7) contains supplementary material, which is available to authorized users. In recent decades, the idea that emotion—affective states that have arousing or motivational properties—might play a role in decision making has been increasingly considered . ResearcClinical decisions are often made in contexts that are emotionally challenging and require clinicians to actively manager their own and others’ emotions. Recently, the authors of a review paper  concludeWhile links have been made between emotions and CDM in the literature, theoretical models of CDM largely focus on the technical and cognitive aspects of reasoning and making decisions. Clinicians’ and others’ emotions are a largely overlooked factor in theoretical models and research on CDM –18. GiveTo further understanding of the role of emotion in CDM, we undertook an integrative review of the literature. For the purposes of the review, clinical reasoning was defined as the thinking processes involved in evaluating and integrating available information within clinical contexts whereas CDM involves choosing among various alternatives to inform patient focussed and evidenced based diagnosis and behaviours. Thus clinical reasoning informs the endpoint of decision making .Traditionally, CDM has been perceived as a “hypothetico-deductive process of determining patients’ problems” , with atIn his ‘Universal Model of Diagnostic Reasoning’ Croskerry  allowed There is recent empirical evidence linking ‘intuitive decision making’ with galvanic skin response , a physiBechara, Damasio, and Damasio  describeThe role of experience was also highlighted in a recent brain imaging study  where paIn addition to the somatic marker hypothesis another decision making model relevant to this paper is that of the appraisal tendency framework (ATF) . Within Traditionally clinical decision making has been perceived as a hypothetico-deductive process, yet there seems to be an association between emotions—and/or emotional competence—and clinical decision making. Current theories of clinical decision making may not sufficiently account for the role of emotions in decision making processes. Therefore, we sought to detail the experience of and behaviours directly related to emotion in the immediate context of clinical decision making.The aim of this review was to identify empirical evidence for the role of emotions and/or emotional intelligence in clinical reasoning and/or clinical decision making.An integrative, systematic review method , 38, briThe first author conducted a computerised search of the bibliographic databases PubMed, PsychINFO, and CINAHL (EBSCO). A health services librarian was consulted for the design of the search strategy. Key subject descriptors and MeSH terms were used to map terms to the database vocabularies. The search terms used were: emotions; emotional intelligence; emotion*; decision making, clinical; clinical decision making; and, clinical reasoning. Limiters were: scholarly journal, English language; and publication 2006-February 2017. Inclusion criteria were: 1) reports empirical data ; 2) concerns clinicians in clinical settings; 3) concerns clinician emotion OR clinician emotional intelligence/emotional competence; 4) concerns the effect or influence or relationship between criterion 3 and clinical decision making OR clinical reasoning. The complete search strategy can be found in Additional file Following removal of duplicates, 479 studies were initially identified from the search strategy. Title and abstract screening was performed, with 38 papers retained. These retained papers were then reviewed at the full-text level. Fig. As no available tool was suited to evaluating the range of study designs included in this review, a modified set of appraisal criteria were derived by synthesising key criteria from pre-existing tools –45. The The final manuscripts retained included quantitative, qualitative and mixed methods research and were suited to integrative synthesis . To deriThe final papers included in the review all concern clinical reasoning and CDM by clinicians. As can be seen in Table Of the retained studies, an explicit intention to examine both emotion and clinical reasoning/clinical decision making was expressed in the aims in only five –70, 12 semotional response to contextual pressures, where clinical contexts of uncertainty, fear, conflict, discomfort, regret and unpredictability served as triggers for increased awareness of one’s own emotion; ii) emotional responses to others, where emotional self-awareness was sometimes described as a gut feeling that triggered the need for action; and, iii), intentional exclusion of emotion from CDM, where emotions were present in CDM, but mostly were not consciously foregrounded in decision making. Each of these themes are described in more detail below.Experienced emotion as an aspect of clinical reasoning and clinical decision making was highlighted in 14 studies –66, 70. n = 10) in the USA, Islam, Weir, Jones, Del Fiol, and Samore [Emotional responses of anxiety, stress and fear were evident where clinicians experienced pressures associated with CDM. In a qualitative study with infectious disease physicians  Interdisciplinary tension regarding the significance and meaning of emotion in CDM, and iii) Emotion and moral judgement. These themes foreground thoughtful integration of emotion and cognition and emotional awareness and emotional management of self and others, along with the skills and behaviours associated with clinicians’ emotional intelligence that were influential in clinical decision making.The complex emotional contexts in which clinical decision making takes place as well as clinicians’ experiences, responses, and emotional/cognitive strategies for dealing with such environments were apparent in a number of the reviewed papers. Three sub-themes emerged from the synthesis: i) . [, in an interview based study of 32 nursing home nurses, included emotion in two of their five main themes related to managing residents’ remaining abilities. They found that CDM was undertaken through holistic cognitive dominated assessment that relied on the underpinning emotional awareness of others. CDM triggered holistic interventions across a physical-emotional spectrum with the inclusion of the emotional context of the patient leading to emotional interventions through emotional reasoning behaviours by the nurses. Gallagher et al. [Alexander et al.  analysed. , in an ir et al.  sought bIn their qualitative study of nurses in abortion care, McLemore et al.  highlighGallagher et al.  further Tensions around power differentials between nursing and medical staff in CDM were evident in the grounded theory study of nurses’ EOL decision making by Bach, Ploeg, and Black . HoweverFactors related to emotional intelligence in CDM have also been explored through quantitative and mixed methods approaches. For example, Alba  measuredDespite the absence of emotion from accepted theoretical models of CDM, this review and synthesis of the empirical evidence found sufficient evidence to conclude that clinicians’ experienced emotions and their perceptions and understanding of others’ emotions can and do influence their decisions. We identified two main themes in the context of clinical decision making: the subjective experience of emotion; and, the application of emotion and cognition in CDM. Sub-themes under the subjective experience of emotion were: emotional response to contextual pressures; emotional responses to others; and, intentional exclusion of emotion from CDM. Under the application of emotion and cognition in CDM, sub-themes were: compassionate emotional labour – responsiveness to patient emotion within CDM; interdisciplinary tension regarding the significance and meaning of emotion in CDM; and, emotion and moral judgement.Medical oriented qualitative studies identified here have an underlying theme of anxiety and stress associated with health care provision and this consciously or unconsciously impacting on clinicians and, hence, on the decisions they make and on how they communicate those decisions. Uncertainty is a key feature of the emotional context of CDM and in medical practice has been strongly associated with stress and fear  with denAdditionally, the medical literature has emotional CDM in the background to procedural based CDM, while nursing literature more strongly figures the emotional and patient advocacy aspects of nursing CDM, as well as wider nursing roles. Although bodily sensations described as gut feelings could be considered a kind of emotional awareness triggering the need for adjustment or action , there iThe acknowledgement and mastery of the emotional aspect of clinical decision making has been suggested as a critical element to improving patient safety . Yet thiThe broad construct of EI is concerned with the effective interaction of accessing and utilising both emotion and cognition to inform behavioural choices . HoweverHowever, this review identified only 5 studies where a consideration of emotion and CDM was an explicit aim. The other retained papers looked at one or other of these elements, or covered them incidentally. This represents a great opportunity for further work on the role of emotion and EI in CDM. The paucity of focus on emotion in empirical work is equally apparent in theoretical models of CDM. Alongside studies intended to explicate more fully the role of emotion and EI in CDM, development of a model of CDM that integrates recognition of the true role/s of emotion and EI skills is needed. We are not the first to call for this, for example, Alba  wrote “rThree opportunities have been identified through this review of primary evidence. Firstly, research designed to provide a more thorough and intentional picture of the ways emotion influences CDM is called for. Secondly, theoretical models of clinical decision making could become more nuanced and externally valid if they incorporated emotional aspects more fully. Finally, a focus on building emotional capabilities in our clinicians, both pre- and post-registration, may be an effective step toward increasing patient safety as well as clinicians’ feelings of self-efficacy. EI appears to be a construct to build such emotional capabilities as it is already associated with improved outcomes in work wellness , lower sClinicians’ experienced emotions can and do affect clinical decision making, although acknowledgement of that is far from universal. We found ample evidence, albeit of variable quality, to confirm that both emotion and cognition are engaged in clinical decision making. Importantly, this occurs in the in the absence of a clear theoretical framework and educational preparation may not reflect the importance of emotional competence to effective CDM.