Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia . Infection is transmitted via the fecal-oral route with most cases and deaths occurring among populations that lack access to safe drinking water and adequate sanitation and hygiene. The illness has nonspecific symptoms, making it difficult to distinguish clinically from other febrile illnesses  for persons aged ≥2 years, and a live attenuated oral Ty21a vaccine available in capsule formulation for persons aged ≥5 years. One ViPS vaccine (Sanofi Pasteur) was prequalified by the World Health Organization (WHO) in 2011, enabling purchase by United Nations agencies; Gavi, the Vaccine Alliance (Gavi); and some international donors.Information on typhoid surveillance during 2009–2013 was obtained from a supplemental survey of surveillance officers and from published reports. Data included information on type of surveillance, level at which surveillance is conducted , age groups, case definitions, and laboratory confirmation. Typhoid vaccination information was obtained from the WHO/UNICEF Joint Reporting Form on Immunization data for 2009–2013, a survey of immunization program managers, and published literature. Data were collected on vaccines used, target populations (excluding travelers) and program strategies. Selected examples of large-scale typhoid vaccination programs also were reviewed. The information available varied in detail, and might not represent current and comprehensive data for all countries reviewed. Data on typhoid surveillance and vaccine use, respectively, were available from 30 (63%) and 31 (65%) of the 48 countries and areas of SEAR and WPR.Overall, 23 (48%) of 48 countries and areas of SEAR and WPR collected data on typhoid cases. Of these, 22 reported that typhoid was a notifiable disease, and 20 conducted surveillance activities, most through passive reporting at the national level . Among tDuring 2009–2013, nine (19%) of 48 countries and areas in SEAR and WPR implemented a typhoid vaccination program or recommended vaccine use (excluding vaccination of travelers) . In mostChina, India, and Vietnam initiated public sector typhoid vaccination programs before 2008, targeting preschool or school-aged children in selected geographic areas . Nepal iBOXCountries should consider the programmatic use of typhoid vaccines for controlling endemic disease.In most countries, only targeted vaccination of high-risk groups and populations will be required.Where appropriate, vaccine use should be harmonized with routine immunization programs.Immunization of preschool and school-aged children is recommended in areas where typhoid is a significant public health problem in these age groups.Given the epidemic potential, typhoid vaccination is recommended for outbreak control.Decisions regarding programmatic use should be based on a detailed knowledge of the local epidemiologic situation and other local factors, such as school enrollment rates, sensitivity of prevailing strains to relevant antimicrobials, and cost-effectiveness analyses.Priority should be given to strengthening surveillance systems for typhoid fever, including sentinel-site surveillance for preschool and school-aged children.Typhoid vaccination programs should be implemented in the context of other control efforts.Health education and health promotion.Training of health professionals in diagnosis and treatment.Improvements in water quality and sanitation.Source: WHO position paper on typhoid vaccines (2008).Despite the substantial and recognized disease burden , progresEstablishing and strengthening typhoid surveillance remains a challenge, and subnational variations in typhoid incidence are common. Among countries for which data were available, the majority reported having typhoid surveillance as part of the national notifiable disease surveillance system, although most often typhoid was included as part of passive reporting of acute febrile illnesses or general infectious diseases. Culture confirmation of suspected and probable cases continues to be limited. Although most countries reported using a standard case definition, the case definitions used varied widely. Available serologic tests, including the Widal test, have limited value because of poor sensitivity and specificity for typhoid diagnosis, and difficulty with standardizing reagents and interpreting values across different settings. Given the challenges in the clinical diagnosis of typhoid fever, updated surveillance standards and guidelines, including standard case definitions and quality assurance and quality control protocols for laboratories, need to be widely disseminated and their use encouraged. Culture confirmation remains the gold standard for typhoid diagnosis; laboratory capacity building  is needed to increase the accuracy of disease reporting and to facilitate monitoring of antimicrobial resistance, which is a growing problem.During 2001–2003, the Diseases of the Most Impoverished Program conducted systematic population-based surveillance across five Asian countries . The disDespite experience with large scale typhoid vaccination studies and successful implementation of programs, vaccine adoption since the revised WHO recommendations was limited in SEAR and WPR. In China and Vietnam, two countries with large-scale typhoid vaccination programs, typhoid incidence was reported to have declined steadily since vaccine use was initiated; improvements to water and sanitation infrastructure also were reported in Vietnam during this time . In FijiWhat is already known on this topic?Typhoid fever is an acute, systemic infection that represents an important cause of morbidity and mortality in the developing world with nearly 22 million cases and 216,500 deaths annually worldwide. Safe drinking water, adequate sanitation, appropriate personal and food hygiene, and typhoid vaccination are the most effective prevention and control strategies.What is added by this report?During the 5-year period after revision of the World Health Organization recommendations for typhoid vaccines in 2008, progress in typhoid surveillance and vaccine use has been limited in the South-East Asia and Western Pacific regions. During 2009–2013, surveillance or notifiable disease data on typhoid cases were collected in 23 (48%) of 48 countries and areas, and typhoid vaccination or recommendation for use was reported by nine (19%) of 48 countries and areas in these two regions.What are the implications for public health practice?Despite the substantial and recognized disease burden, typhoid fever remains a neglected disease in both the South-East Asia and Western Pacific regions. Coordinated action involving key stakeholders and partners at the regional and national levels is needed to create appropriate typhoid fever prevention and control policies and strategies, especially in settings with high incidence of disease.Although the reasons for low typhoid vaccine use are not fully documented, multiple factors might have contributed. Countries might require data to ascertain local disease burden and to identify high-risk populations, for whom the recommended vaccination strategies apply, and lack of such data might be an impediment to justify vaccination programs. As countries introduce multiple new vaccines in their national immunization programs, typhoid vaccination might be a lower priority or lack adequate national or donor funding. Vaccine supply might be another potential barrier. For example, in 2012, Sanofi Pasteur recalled certain lots of the ViPS vaccine, which remains the only typhoid vaccine prequalified by WHO. An assessment of vaccine supply from both international and domestic manufacturers in multiple countries and country level policies regarding licensure and use, could help to elucidate supply and use constraints. Evaluation of typhoid vaccine impact in a variety of epidemiologic and programmatic contexts might contribute to the evidence to increase vaccine use.Newer generation typhoid conjugate vaccines (TCVs) are under development, and when available, will be considered for funding support by Gavi. These vaccines are expected to have several advantages over ViPS and Ty21a vaccines, in particular, the potential to be immunogenic in children aged <2 years (facilitating incorporation in routine childhood immunization programs), to provide a booster effect (currently lacking for the ViPS vaccine), and a longer duration of protection. Two conjugate vaccines are licensed and being used in the private sector in India, and a third is undergoing licensure review in China. Seven additional TCV candidates are currently in different stages of preclinical and clinical development. Ongoing efforts aim to develop bivalent typhoid-paratyphoid vaccines to prevent enteric fever as a whole.WHO recently convened a group of experts to review the available clinical data on TCVs.


Background: Gender based violence (GBV) remains one of the most serious threats to the health and safety of women and girls worldwide. The problem is even more pronounced in refugee populations where women and girls are at increased risk of violence. In 2015, UNHCR reported the highest number of forcibly displaced people in recorded history. Despite growing need, there have been few rigorous evaluations of interventions aimed at primary GBV prevention and no systematic reviews of GBV prevention efforts specifically focused on refugee populations; reviews to date have primarily examined prevention of conflict related sexual violence, with very limited focus on other forms of GBV such as intimate partner violenceMethods: This study reviewed the scientific literature addressing strategies for primary prevention of GBV and their effectiveness among refugee populations over the past ten years (2006 to 2015). Narrative content analysis methods were used to extract findings related to prevention activities/programs recommended by the global humanitarian community, such as sociocultural norms change, rebuilding family and community support structures, improving accountability systems, designing effective services and facilities, working with formal and traditional legal systems, monitoring and documenting GBV, and/or engaging men and boys in GBV prevention and response.Results: Study findings indicate that a range of GBV prevention activities recommended by the global humanitarian community are currently being applied in a variety of settings. However, there remains a limited body of evidence on the effectiveness of GBV prevention programs, interventions, and strategies, especially among refugee populations.Conclusion: Commonly agreed upon standards or guidelines for evaluation of GBV prevention programming, and publication of evaluations conducted using these guidelines, could assist humanitarian stakeholders to build and disseminate an evidence base of effective GBV prevention interventions, programs and strategies. Evaluation of GBV prevention efforts, especially among refugee populations, must be given higher priority to justify continuation or revision of recommended GBV activities/programs being implemented in diverse humanitarian settings. Gender-based violence (GBV) remains one of the most prevalent and persistent issues facing women and girls globally ,,The World Health Organization (WHO) estimates that 35% of women experience some kind of physical and/or sexual violence at some point in their lives ,,,,,The displaced population at risk of GBV continues to grow in parallel with the size of the population displaced by conflict which is presently estimated at 59.5 million forcibly displaced worldwide, which is the highest levels recorded since the end of World War II Six types of GBV prevention programming identified in UNHCR’s 2003 Sexual and Gender-Based Violence against Refugees, Returnees and Internally Displaced Persons: Guidelines for Prevention and Response are as follows (1) Transforming socio-cultural norms, with an emphasis on empowering women and girls(2) Rebuilding family and community structures and support systems(3) Creating conditions to improve accountability systems(4) Designing effective services and facilities(5) Working with formal and traditional legal systems(6) Assessment, monitoring, and documentation of GBVThe guidelines recommend involving men as a key strategy for transforming socio-cultural norms and highlight the importance of equal participation by women, men, girls, and boys in planning, implementing, monitoring, and evaluating programs. Over the last decade, there has been increasing attention to the fact that men’s roles and relationships to GBV in conflict and post-conflict situations include that of perpetrators, victims, witnesses and agents of change, and that male engagement is an essential component of GBV prevention and response programming in humanitarian settings ,Although there has been an increase in the number of programs in refugee populations to prevent and respond to GBV, particularly sexual violence against women and girls, there remains a general lack of evidence regarding the effectiveness of these efforts in preventing diverse forms of GBV, and a lack of evaluation of efforts outside of conflict related sexual violence Recent evaluations of humanitarian programs have also highlighted the need for evidence on effective GBV prevention strategies. For example, a recent evaluation in Syria of the implementation of the Inter-Agency Standing Committee (IASC) Guidelines for Gender-Based Violence Interventions in Humanitarian Settings found that IASC guidelines were not well known nor being used in programmatic practice, and while there have been ‘high level’ statements that prevention and response efforts require involvement at many levels and types of actors, there is lack of practical guidance about how to incorporate GBV prevention programming across diverse humanitarian sectors, such as health, water and sanitation, education, and livelihood programs An integrative review of scientific literature on GBV prevention was initially conducted in 2013 and later updated in October 2015 using the following databases: Pubmed, Scopus and Web of Science. The search was limited to studies published in English over the previous ten years (i.e. 2006 to 2015). Key search terms were identified through a preliminary review of relevant literature in consultation with a public health information specialist at the Johns Hopkins University Welch Medical Library. A summary of search terms, databases, inclusion criteria and other information on the selection strategy is presented in Screening of LiteratureFollowing removal of duplicate articles (i.e. articles listed in multiple databases), two independent reviewers conducted a multi-stage title and abstract screening process to determine each study's eligibility for inclusion in the review. In the first round of screening, any study that met the three inclusions criteria were included for further review, regardless of study design. To ensure no potentially relevant studies were omitted, titles and abstracts of excluded studies were then re-screened and any studies focused on specific GBV prevention interventions, programs or strategies among non-refugee populations in crisis-prone, crisis-affected, or low-resource settings that could inform GBV prevention in refugee populations were included . All studies that met content-based inclusion criteria were included, regardless of the study design, quality or potential risk of bias.Data Extraction and SynthesisAll included studies were reviewed in detail and coded according to their relevance to the seven types of primary prevention programming mentioned above: transforming socio-cultural norms, with an emphasis on empowering women and girls; rebuilding family and community structures and support systems; creating conditions to improve accountability systems; designing effective services and facilities; working with formal and traditional legal systems; assessment, monitoring, and documentation of GBV; and engaging men and boys in GBV prevention and response.Key findings related to each type of primary prevention programming were analysed separately using narrative content analysis techniques, and then results combined to provide an overall synthesis of publications related to GBV prevention in refugee populations.Ethical ReviewThis review did not involve any primary data collection and thus did not require review by an Institutional Review Board or ethics committee.A total of 618 articles were identified. After removal of duplicates, 393 articles were included in the title/abstract review. Of the 393 articles initially identified for review, only ten met all three inclusion criteria, including: 4 reviews, five qualitative studies, and one mixed methods stud. In addition, thirteen articles on GBV prevention in non-refugee populations were identified as relevant (see previously defined screening methods) and were included in full text review , includiA total of twenty-three peer-reviewed articles were identified for data extraction and included in the review ,. EvaluaA total of twenty-three peer-reviewed articles were identified for data extraction and included in the review ,. EvaluaKey findings pertaining to the peer-reviewed literature , organized by types of prevention programming, are as follows:(1) Transforming socio-cultural norms, with an emphasis on empowering women and girlsNone of the peer-reviewed articles identified through the systematic search addressed gender transformative programming or presented research on interventions seeking to address socio-cultural norms in refugee settings. A number of studies in other settings, however, sought to gain an understanding of gender norms and evaluate gender-transformative interventions, specifically addressing conceptions of masculinity seen as factors in GBV. For example, one community-based study in South Sudan found that both men and women agreed with gender-inequitable norms, for example, husband has the right to demand sex from wife, men need more sex then women, it is more important to educate boys than girls, which provides further support for GBV programming addressing the attitudes of both women and men (2) Rebuilding family and community structures and support systems,None of the peer-reviewed articles specifically addressed an intervention aimed at family and community structures and support systems in refugee or non-refugee settings. However, two studies (3) Creating conditions to improve accountability systems,,Three of the ten peer-reviewed articles (4) Designing effective services and facilitiesNone of the articles reviewed present proven or well-established practices for effectively preventing GBV in refugee settings, and one of the studies indicated that the single biggest barrier to implementation was the absence of evidence-based interventions ,Two of the ten peer-reviewed articles in displacement settings discuss gaps in reproductive health service provision, including gaps in adherence to international guidelines and standards for prevention and response to GBV ,There is a limited but growing body of evidence on effective GBV prevention models in non-refugee settings. The most commonly referenced example is the Intervention with Microfinance for AIDS & Gender Equity (IMAGE), which combines microfinance with a participatory gender and HIV training curriculum for rural women in Limpopo Province, South Africa. An evaluation of the intervention found that program participants experienced a 55% reduction in physical and/or sexual violence by an intimate partner relative As indicated in one study (5) Working with formal and traditional legal systemsNone of the peer-reviewed articles focus on working with formal and traditional legal systems in refugee settings. However, one article (6) Assessment, monitoring, and documentation of GBV,None of the articles reviewed present methods for measuring or evaluating the effectiveness of GBV prevention programming in refugee settings, though several articles did address barriers as well as enabling factors for documentation of GBV. The two articles assessing health service provision for GBV survivors (7) Engaging men and boys in GBV prevention and response,,,None of the peer-reviewed articles focus on engaging refugee men and boys in GBV prevention and response. However, there is a limited but growing body of evidence on engaging men and boys in GBV prevention and response in other settings. Impact and process evaluations of programs using participatory group education to change norms associated with violence have shown positive results; some of these programs involve women and men to change norms associated with GBV The available research also suggests that programs aiming to empower women economically should be attentive to the possibility that men who perceive themselves to be economically vulnerable or marginalized are already, in some settings, more likely to commit GBV. If economically marginalized men view their traditional roles as “heads of households” being eroded by women’s income-generating activities, engaging men in a deliberate questioning of such roles can enable them to embrace cooperation and sharing of activities at the household level ,,,A 2006 a review of 58 evaluations of engaging men and boys in GBV prevention and health programming found that programs that promote gender-equitable relationships between men and women by engaging men in discussions of gender and masculinity with deliberate efforts to transform gender norms may be more effective in producing behavior change than more narrowly focused interventions that merely acknowledge gender norms and roles There is a limited body of evidence available on effective GBV prevention strategies, especially in refugee settings. This gap is more pronounced with regards to prevention of forms of GBV other than sexual violence as an act of war, including intimate partner violence. Few of the articles reviewed provided objective data to showing the effectiveness of interventions and findings of those that did may not be generalizable. None of the peer-reviewed articles identified in the review presented proven strategies for addressing socio-cultural norms, rebuilding family and community support structures, improving accountability systems, designing effective services and facilities, working with formal and traditional legal systems, monitoring and documenting GBV, or engaging men and boys in GBV prevention and response in refugee settings.,This evidence gap may be related to both the challenge of conducting research on GBV prevention efforts and difficulties of conducting impact evaluations in humanitarian settings. For example, there are ethical considerations in conducting long-term evaluation of displaced populations, and shifting organizational priorities and donor funding may limit the duration of GBV programs. Additionally, security and logistical challenges are typically present in refugee settings. Limitations in the availability of staff, training, expertise, and funding for GBV programs in displacement settings are also common As indicated by previous GBV reviews, and particularly those focused on sexual violence against women and girls, there remains a clear gap in the quality and availability of impact evaluations for past and present interventions focused on GBV prevention more broadly, and this gap is even more pronounced for refugee populations. As a consequence of the general lack of published literature on GBV prevention in refugee populations, the inclusion of articles focused on GBV prevention in non-refugee populations  was considered necessary. Evaluations of GBV prevention efforts in non-refugee settings may not be generalizable to refugee populations where the risk profile and contextual factors may be different. Given the varied populations, interventions, and study designs of included studies, findings were given equal consideration in analysis, regardless of the study design, quality or potential risk of bias.This study provides an integrative review of scientific publications related to GBV prevention in refugee populations that goes beyond the scope of previous reviews and compares the availability of evidence for different types of GBV prevention activities recommended by the global humanitarian community. Whereas previous reviews addressing refugee populations has focused on conflict related sexual violence, this study expands scope of the literature to review socio-cultural norms change, rebuilding family and community support structures, improving accountability systems, designing effective services and facilities, working with formal and traditional legal systems, monitoring and documenting GBV, and/or engaging men and boys in GBV prevention and response in refugee settings. Upon examination, there were few studies providing evidence of effective GBV prevention strategies or interventions, suggesting that there is little research conducted on the effectiveness of GBV prevention efforts in humanitarian settings or that evaluations of these programs are rarely published in peer-reviewed scientific literature. This supports Asgary et al’s findings The authors have declared that no competing interests exist.


HealthyPeople2020, and the recent launch of the precision medicine initiative. The Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC) partners with state public health departments and others to advance the translation of genome-based discoveries into disease prevention and population health. To do this, OPHG has adopted an “identify, inform, and integrate” model: identify evidence-based genomic applications ready for implementation, inform stakeholders about these applications, and integrate these applications into public health at the local, state, and national level. This paper addresses current and future work at OPHG for integrating genomics into public health programs.The national effort to use genomic knowledge to save lives is gaining momentum, as illustrated by the inclusion of genomics in key public health initiatives, including  HealthyPeople2020 includes Genomics as a new topic area, with the following objectives: (1) increase the proportion of women with a family history of breast and/or ovarian cancer who receive genetic counseling; and (2) increase the proportion of persons with newly diagnosed colorectal cancer who receive genetic testing to identify Lynch syndrome  [BRCA genetic counseling is a preventive service covered by many insurers under the Affordable Care Act in accordance with the U.S. Preventive Services Task Force (USPSTF) recommendation [The increasing prioritization of genomics in public health is reflected in the inclusion of genomics in key public health initiatives. Pathogen genomics has been used in public health for decades and has been integrated into Centers for Disease Control and Prevention (CDC) activities, most recently through the Advanced Molecular Detection Initiative, which addresses the applications of pathogen genomics methods and technologies . For thiendation ,4,5. Staendation . The Preendation . “Precisendation . FurtherHealthyPeople2020 [HealthyPeople2020 goals of increased identification and provision of genetic services for individuals at risk for Hereditary Breast and Ovarian Cancer (HBOC) and Lynch syndrome and help define the role of “precision public health.” OPHG works to promote effective and responsible translation of genome-based discoveries into disease prevention and population health. To do this strategically, OPHG has adopted an “identify, inform, and integrate” model: identify evidence-based genomic applications ready for implementation, inform stakeholders about these applications, and integrate these applications into public health at the local, state, and national level. In this paper, we will describe current and future work at OPHG and how these projects contribute to the “identify, inform, and integrate” model. This work includes activities based on horizon scanning, guidelines, informatics, and support of state genomics programs.Since its inception in 1997, the Office of Public Health Genomics (OPHG) at the CDC has worked with state health departments and other partners to identify opportunities for genomics to improve population health and provided foundational contributions to help support genomics-related public health activities. These activities include establishment of the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group, whose recommendations on Lynch syndrome are cited in ple2020 ,11. CurrOPHG uses a systematic literature research method called horizon scanning ,13, whicPromoting the need for a robust evidence base for genomic applications has been a consistent theme for OPHG. Inspiration was drawn from the successes of groups such as the US Preventive Services Task Force, The Guide to Community Preventive Services, The Cochrane Collaboration, and many others, as powerful indicators for the value of evidence-based evaluation to support rational integration of genomics in health. The ACCE  model process was an early initiative supported by OPHG to promote the development and use of targeted and balanced methods in evidence synthesis . AlthougOPHG sponsored the EGAPP initiative to put the lessons learned from development of the ACCE model into action. In addition to the ACCE criteria, EGAPP also considers clinical factors, test availability, cost effectiveness, and other contextual factors in making recommendations. EGAPP is an ongoing effort to develop and apply evidence-based evaluation practices in the field of genomic health. The initiative has been centered on the independent EGAPP working group, which has developed, refined, and tested a plethora of methods for evaluation of genomic tests. Since 2007, the EGAPP working group has published nine recommendation statements, three methods reports, and an article describing the lessons they have learned throughout the process . EGAPP rExtending the foundational work of EGAPP toward realizing population health benefits of evidence-based recommendations requires new efforts to bring public health, health care, and other stakeholders together to: (1) accelerate research translation and implementation of genomics; (2) develop and apply methods for assessing best practices and outcomes for implementation of genomic applications and their impact in the real world; (3) assemble and enhance metrics, tools, and education materials that can increase uptake of genomic applications in health care and disease prevention and for informing and engaging providers, policy makers, and the general public; and (4) develop pilot projects for implementation of genomic applications at the interface of public health and healthcare, with a focus on surveillance and measurement, policy impact, education, and programs.State public health departments are essential partners in the national effort to use genomic knowledge to save lives. CDC has provided both financial and technical support to states implementing genomics approaches to public health. In 2003, the year of the completion of the Human Genome Project, CDC issued five-year cooperative agreements with the purpose of integrating genomics into state based public health policy and programs. The four awardees, Michigan, Minnesota, Oregon, and Utah, pursued this goal successfully using different approaches. These states soon became pioneering examples for generalizable public health genomics implementation efforts which included: (1) promoting planning both internally and with outside partners to use genomic information, including genetic testing and family history data, in existing policy and programs; (2) developing workforce capacity and leadership for application of genomic knowledge and technologies to chronic, infectious, and environmental diseases; (3) establishing leadership for genomics integration into plans and prevention programs for asthma, cancer, cardiovascular disease, and diabetes; and (4) developing evidence for the use of genomics in disease prevention and established sustainable interventions involving family health history collection, assessments, and educational curricula and materials for the health workforce, policymakers, and the public .BRCA recommendation, with states developing model programs such as using cancer registry data to educate health care providers and institutions about patients in their care who could benefit from evidence-based genetic testing recommendations [When this trailblazing agreement was completed, OPHG, CDC issued new three-year cooperative agreements in 2008 which built upon the infrastructure developed in the previous cycle, while focusing on opportunities to use public health strengths of surveillance, education, and policy development to promote and monitor implementation of newly emerging evidence-based genomic testing and family health history recommendations. Activities focused on supporting implementation of the 2005 USPSTF ndations . MichigaHealthyPeople2020 Action Award.Model state activities similar to those initiated under the 2008 CDC cooperative agreements received support through two Division of Cancer Prevention and Control (DCPC), CDC funding opportunities awarded in 2011 and 2014 to Michigan, Oregon, Georgia, and Utah . In addiHealthyPeople2020 objective; and (4) designing and implementing educational outreach programs targeting the general public and health professionals about Tier 1 applications. A limited number of Phase 2 approaches are described. Tools and educational materials developed by OPHG and states are listed. The section on Lynch syndrome includes state-by-state estimates of the number of people with Lynch syndrome who could be identified by screening all persons with newly diagnosed invasive colorectal cancer.These CDC-funded state activities served as model programs and informed the development of resources and tools to assist other states in implementing genomics approaches in public health. These tools include the State Implementation Activities Clickable Map and the Genomics Toolkit. The State Implementation Activities Clickable Map provides state-by-state information on activities related to implementation of three Tier I public health genomics applications: Hereditary Breast and Ovarian Cancer (HBOC), Lynch Syndrome, and Familial Hypercholesterolemia (FH), as well as general information on state public health genomics programs. The Tier 1 Genomic Applications Toolkit for Public Health Departments describes genomics approaches used by model state programs. The Toolkit outlines key first steps that state public health departments can take to identify existing state priorities and activities related to genomics. These steps include identifying objectives related to Tier 1 applications in the state comprehensive cancer control plan and heart disease and stroke plan, reviewing existing Tier 1 activities and resources in the state using the State Implementation Activities Clickable Map, and choosing projects based on the successful examples provided in the Toolkit. Approaches discussed in the Toolkit are divided into Phase 1 and Phase 2. Phase 1 approaches focus on identification of individuals who could benefit from Tier 1 genomic applications, while Phase 2 approaches expand to finding at-risk family members of these individuals through cascade screening. These risk identification activities fulfill a major aim of precision public health. The Toolkit includes basic information on each of the three Tier 1 conditions and the current Tier 1 recommendation. The Toolkit provides examples of Phase 1 approaches implemented by state health departments: (1) use of cancer registry data to identify individuals at high risk for Lynch syndrome and Hereditary Breast and Ovarian Cancer syndrome ; (2) informing policy making, such as evidence-based coverage by payers for services specified by Tier 1 recommendations; (3) developing and tracking surveillance indicators to follow progress in achieving widespread implementation of Tier 1 recommendations and the OPHG recently partnered with Genetic Alliance  to develWith continued advances in genomics, we are seeing an increasing number of genomic applications that can be used in public health programs. Through the ongoing activities summarized above, OPHG is able to fulfill its mission to identify, inform, and integrate evidence-based genomic testing and family health history applications to realize health impact. The horizon scanning process identifies genomic applications at different stages of translation. The database currently in development will provide a valuable resource to inform stakeholders about key applications in genomics, with searchable databases for guidelines, articles on translation of genomic applications, human genome epidemiology literature, CDC resources, and other items. The Tier Classification of Genomic Applications by Levels of Evidence and Weekly Update serve to inform key stakeholders about genomic approaches and their readiness for implementation. OPHG supports integration of those applications ready for translation through EGAPP and similar initiatives and by providing resources to states such as the clickable map and toolkit.OPHG is actively exploring emerging opportunities to integrate genomic applications in public health. OPHG has written a journal article  and blog


Six key steps for effective transition: (1) develop a roadmap; (2) involve stakeholders; (3) communicate the plan; (4) support midterm evaluations; (5) strengthen financial, technical, and management capacity; and (6) support ongoing M&E. The Eastern Caribbean will need to identify HIV champions; strengthen leadership and management; improve policies to protect key populations; engage the private sector and civil society more; integrate HIV programs into primary care; improve supply chain capacity; and address health worker shortages. Six key steps for effective transition: (1) develop a roadmap; (2) involve stakeholders; (3) communicate the plan; (4) support midterm evaluations; (5) strengthen financial, technical, and management capacity; and (6) support ongoing M&E. The Eastern Caribbean will need to identify HIV champions; strengthen leadership and management; improve policies to protect key populations; engage the private sector and civil society more; integrate HIV programs into primary care; improve supply chain capacity; and address health worker shortages. The US President’s Emergency Plan for AIDS Relief (PEPFAR) has shifted from an emergency response to a sustainable, country-owned response. The process of transition to country ownership is already underway in the Eastern Caribbean; the Office of the US Global AIDS Coordinator (OGAC) has advised the region that PEPFAR funding is being redirected away from the Eastern Caribbean toward Caribbean countries with high disease burden to strengthen services for key populations. This article seeks to highlight and apply lessons learned from other donor transitions to support a successful transition of HIV programs in the Eastern Caribbean. Based on a rapid review of both peer-reviewed and gray literature on donor transitions to country ownership in family planning, HIV, and other areas, we identified 48 resources that addressed key steps in the transition process and determinants of readiness for transition. Analysis of the existing literature revealed 6 steps that could help ensure successful transition, including developing a clear roadmap articulated through high-level diplomacy; investing in extensive stakeholder engagement; and supporting monitoring and evaluation during and after the transition to adjust course as needed. Nine specific areas to assess a country’s readiness for transition include: leadership and management capacity, political and economic factors, the policy environment, identification of alternative funding sources, integration of HIV programs into the wider health system, the institutionalization of processes, the strength of procurement and supply chain management, identification of staffing and training needs, and engagement of civil society and the private sector. In the Caribbean, key areas requiring strengthening to ensure countries in the region can maintain the gains made under PEPFAR include further engaging civil society and the private sector, building the capacity of NGOs to take on essential program functions, and maintaining donor support for targeted capacity building and long-term monitoring and evaluation efforts. The US President’s Emergency Plan for AIDS Relief (PEPFAR) has helped introduce lifesaving treatment to 7.7 million people living with HIV (PLHIV) worldwide.The Sustainability Agenda, a key dimension of PEPFAR 3.0’s new business model, acknowledges that long-term epidemic control and maintenance of the progress to date will require country-owned responses.PEPFAR’s new business model recognizes that long-term control of the HIV epidemic will require country-owned responses.In 2013, in preparation for regional PEPFAR planning, the US Agency for International Development (USAID) Mission in Barbados and the Eastern Caribbean requested assistance from Abt Associates in framing the transition of PEPFAR programming to country ownership in the Caribbean with an eye toward greater sustainability . SpecifiFor the purposes of this review, we used the Global Health Initiative's definition of country ownershipthe continuum of actions taken by political and institutional stakeholders in partner countries to plan, oversee, manage, deliver, and finance their health sector. These actions advance sustainable, quality health programs that are locally owned and responsive to the needs of host country nationals.… We acknowledge that country ownership requires a comprehensive response from the public, private for-profit, private not-forprofit, and civil society communities. We define “transition to country ownership” as the conscientious shifting of donor-led health initiatives to country ownership.This article helps support these new developments by identifying themes and lessons learned from our literature review to successfully plan, develop, and implement transition strategies that can translate across all PEPFAR countries. Many of the determinants for successful transition identified in the literature closely align with those outlined in PEPFAR’s recent guidance.Comprised of a series of small island nations and mainland countries, the Caribbean has the second highest regional HIV prevalence rate in the world behind sub-Saharan Africa. Adult HIV prevalence among Partnership Framework countries, namely Antigua and Barbuda, Bahamas, Barbados, Belize, Dominica, Grenada, Jamaica, St. Kitts and Nevis, St. Lucia, St. Vincent and the Grenadines, Suriname, and Trinidad and Tobago, is approximately 1%. The epidemic is primarily concentrated among key populations, including commercial sex workers (CSWs), men who have sex with men (MSM), and prisoners.The HIV epidemic in the Caribbean is concentrated primarily among commercial sex workers, men who have sex with men, and prisoners.,The Caribbean’s geopolitical, economic, and cultural context presents unique challenges when planning sustainable, country-owned responses. Although the region is comprised predominantly of middle-income countries, many of the countries rely significantly on PEPFAR funding for HIV programming. For example, recent national health accounts exercises in Dominica and St. Kitts and Nevis indicate that international donors provide 27% and 47% of HIV funding, respectively.Small population bases limit the number of qualified health workers available to implement HIV interventions. With the exception of Jamaica , English-speaking Caribbean countries meet the World Health Organization’s benchmark of 25 trained health professionals  per 10,000 population.Culturally, small population sizes with largely conservative religious influences reduce confidentiality and cultivate widespread stigma and discrimination against PLHIV. This is exacerbated by conservative public policies that outlaw transactional sex and criminalize homosexuality. The result is largely isolated key populations unwilling or unable to access essential HIV prevention, care, and support services from the public health sector. This has placed the onus of reaching key populations on an NGO sector that is often small and fragmented. Since the beginning of the Partnership Framework, PEPFAR has helped these NGOs deliver HIV prevention interventions to nearly 57,000 individuals in key populations.NGOs, with support from PEPFAR, have been instrumental in reaching key populations with HIV services.We sought to answer the following question:What lessons can be drawn from existing literature to help ensure an effective transition of HIV programs to country ownership, and what determinants can be used to assess the Caribbean’s readiness for such a transition?To answer this question, we conducted a rapid review of both peer-reviewed and gray literature with expansive search terms to reflect the shifting language and changing contexts around donor transitions to country ownership. We initially focused on articles discussing the “withdrawal” of donor funding but later expanded the search terms to include “country ownership,” “graduation,” and “sustainability” to address the expanding definition of transition beyond self-financing HIV programs. For example, USAID’s transition away from funding large family planning programs in Latin America and the Caribbean is typically referred to as graduation. While the term graduation was also used in early discussions around PEPFAR transitions, there has been a steady movement in the dialogue toward country ownership, country-owned responses, and sustainability. We searched Google and PubMed for English-language publications using combinations of these terms to ensure a more comprehensive literature review .Using these search terms, we scanned existing literature, including reports, case studies, and scholarly journal articles, and reviewed abstracts and executive summaries to determine relevance to the research question. Those selected for inclusion focused on the shifting dynamic of health programming between one or more donor agencies and partner countries and addressed at least one of the following questions:What does or could transition to country ownership mean within the PEPFAR context?What are key steps in the transition to country ownership?What actions make for a successful transition to country ownership?We identified 48 resources that matched these criteria . Then weOur analysis of existing literature revealed a series of 6 key steps in planning an effective transition to country ownership: (1) develop a roadmap; (2) invest in stakeholder participation; (3) communicate the plan through high-level diplomacy; (4) support midterm evaluations; (5) provide technical assistance throughout the process; and (6) provide long-term monitoring and evaluation (M&E) support.,all HIV program areas. This is a critical lesson for Caribbean roadmap development, as prevention programs are widely supported by international donors.Concise roadmaps are necessary to clearly communicate transition goals and processes. Findings from the literature revealed a lack of clarity among stakeholders about what transition to country ownership meant in practical terms. A clear strategy did not exist in the early stages of graduation from family planning programming in the 1990s; a published review of those early graduations revealed that formal strategies were essential to successful transitions, resulting in establishment of a systematic process by 2004.Roadmaps are needed to clearly communicate transition goals and processes.One potential approach to optimize success is to develop 2 separate roadmaps. The first roadmap could be within PEPFAR to outline the basic process for transition planning. For example, PEPFAR’s “FY2014 Sustainability Planning Guidance Document: Advancing Country Ownership in PEPFAR III” (“Sustainability Planning Guidance”) outlines PEPFAR’s approach to achieving high-impact national HIV responses that maintain service levels and quality under the ownership of “government, civil society, the private sector, and other stakeholders in the partner country.”–Stakeholder participation is a vital component of any successful transition-planning process.Involving stakeholders in the planning process increases the chances of their buy-in but requires more time for the transition.,Intensive stakeholder participation will require a longer time frame for transition. According to Slob and Jerve, no less than 2 years is required to sufficiently involve the full set of key stakeholders in the transition-planning process.,,Leaders from donor and recipient countries should be viewed as active partners with shared, consistent core messaging around why and how transition will happen.,,Midterm assessments provide an opportunity to validate initial assumptions underlying transition plans and to respond to emerging challenges. Early reviews of family planning graduations found that the most successful transition plans were flexible to accommodate changing needs and contexts, oftentimes identified via midterm assessments.The most successful transitions are often flexible to accommodate changing needs and contexts identified through midterm assessments.According to Slob and Jerve, institutional capacity to manage donor withdrawal is a key factor in determining transition success. Initial assessments of financial and technical capacity can help tailor an appropriate roadmap for donor withdrawal and reveal which areas require additional support to fully manage HIV activities and integrate them into national health plans.,,A sustainable program is one in which a country can maintain or improve priority health outcomes. The outcomes can be compromised by new health challenges, unexpected instability, or overestimation of in-country capacity after donor withdrawal. Not all countries have the financial resources and technical expertise to measure these outcomes. Population-based surveys, such as the Demographic and Health Surveys (DHS), are usually sponsored by donors. Supporting ongoing M&E will be especially important in the Caribbean where accurate seroprevalence data is scarce. Ongoing funding for research and health outcomes measurement should be incorporated into the transition roadmap to assist the country in monitoring progress, to help measure the USG’s own success in transitioning, and to contribute to global health research agendas.In February 2015, PEPFAR released new guidance for developing country/regional operational plans, including a “Sustainability Index and Dashboard” (SID) tool to assess sustainability of country programs toward control of the HIV epidemic.This section expands on existing guidance by describing 9 key areas, based on findings from the literature, which should be evaluated when determining readiness for transition to country ownership. We also apply these principles to the Caribbean’s unique regional context to assess readiness and potential barriers to success that may require additional support. Examples focus on countries in the Organization of Eastern Caribbean States (OECS) .,,Country ownership of the national HIV response requires identifying advocates who will promote the cause.A sustained, country-owned response to HIV requires champions who will be advocates for the cause.–,,–Most research on sustainability and country ownership has highlighted the need for increased management capacity. Where PEPFAR has provided more direct provision of services, local partners may need further training in such key management areas as health planning, M&E, procurement, performance management, and financial management.,Political and economic factors have consequences for health outcomes and programming. Jamison et al. note there is a clear economic argument for investing in health. Reductions in mortality account for about 11% of recent economic growth in low- and middle-income countries, and a more comprehensive understanding of the economic value of investing in health provides a strong rationale for improved resource allocation across all sectors.Policies and laws are important in outlining a country’s vision and communicating and regulating the role that local actors can play. Having appropriate policies in place to protect vulnerable populations, regulate the health sector, and provide guidance on the vision for HIV services are key indicators of the readiness of a country for transition. A critical lesson learned from family planning graduation programs is that policies are needed to protect the rights of individuals to access essential services.In the Caribbean, key policy areas to examine during transition are national strategic plans for health (inclusive of HIV), guidance and regulation for private-sector providers (for-profit and not-for-profit) of HIV services, and policies that protect the rights of vulnerable populations. Many Caribbean islands have allowed their strategic plans to lapse and have difficulty resourcing a thorough planning process. Many also lack policies to protect PLHIV and key populations.Policies that protect the rights of vulnerable populations should be examined when transitioning HIV programs to country ownership.,,,Governments must identify ways to replace donor funding.HIV services in the Caribbean are often separate from other primary care services, which could perpetuate stigma.Most Caribbean countries are undergoing health reforms to identify funding sources for soaring health care costs. Not all have determined what these reforms will look like nor have they conducted the research needed to make informed decisions. Several countries are considering national health insurance schemes and wish to design essential packages of services under those schemes. As a component of investment framework guidance from the Joint United Nations Programme on HIV/AIDS (UNAIDS), OECS countries have conducted quantitative analyses of trends in the HIV epidemic, the impact of prevention and treatment efforts to date, and a projection of possible future programming scenarios and their implications for the epidemic and program costs. The exercise produced strategic information to prioritize resources based on largest impact and spurred dialogue on identifying alternative funding sources in advance of transition.Bossert asserts that the sustainability of donor-funded programs relies on effective integration of programs into existing administrative structures.,,To encourage sustainability, any process integral to a program needs to be institutionalized and standardized.Health systems and private-sector assessments conducted in 6 OECS countries revealed that HIV programs are often more likely to have standardized procedures than programs in other health areas. This is especially true for M&E of antiretroviral therapy (ART) provision because it is driven by donor requirements and funding. Further support may be needed to develop and increase the use of standard treatment protocols and to regulate private facilities, including labs that provide testing for HIV. A Caribbean transition plan could provide further support to integrate and streamline the standards, guidelines, and M&E structures from HIV programs into the overall practice of the Ministries of Health.,,Pharmaceuticals and other commodities are an important part of ensuring access to HIV testing and treatment. This is an area in which international donors, especially the USG and the Global Fund, have made substantial investments. PEPFAR’s Track 1.0 ART program helped Ministries of Health in 13 countries strengthen supply chain management and antiretroviral (ARV) procurement. By 2011, the program had been successfully transitioned to country ownership and was providing ART for more than 925,000 patients.The USG has consistently supported procurement and supply chain management efforts in the Eastern Caribbean, including establishment of the OECS Pharmaceutical Procurement System (PPS). While research has shown that pooled procurement does not always result in the expected price drops due to market consolidation and the influence of a smaller number of producers, the OECS has experienced positive gains.–,,,The capacity and retention of skilled workers is essential to ensuring a smooth transition from donor support.,The Caribbean region has long suffered from brain drain, especially among nurses.,In many countries, private-sector providers and NGOs have played a large role in delivering services, monitoring quality of public services, and/or advocating on behalf of marginalized groups. For example, NGOs and the for-profit private sector have played a large role in providing contraceptives. As a result, USAID focused its family planning graduation on developing sustainability of and business plans for private-sector providers to continue offering these services.In many countries, private providers and NGOs play a large role in delivering HIV services, especially to marginalized populations.,In cases where NGOs or private providers are delivering HIV services, transition will require them either to develop their own sustainability plans or to align with government norms to function under government auspices.The current and potential role of the private health sector to deliver HIV services in the Caribbean is vast. The NGO community performs a critical outreach function that provides prevention, counseling, testing, and other services to the populations most vulnerable to HIV. This service is often not feasible through public-sector facilities that are challenged by policies that criminalize the behaviors of key populations and prevent youth from accessing services without parental consent. Members of key populations may be reluctant to go to public-sector clinics for fear of limited confidentiality and the stigma associated with seeking services from the few facilities at which HIV is treated. Despite their critical role in national HIV responses, many Caribbean NGOs are either volunteer-based or heavily reliant on donor funding. For example, while the Caribbean HIV/AIDS Alliance (CHAA) was the leading provider of outreach services for key populations on most of the Eastern Caribbean islands, it was more than 95% reliant on PEPFAR funding.Key population groups may be reluctant to seek HIV services from the public sector for fear of limited confidentiality and of stigma.–Private health care providers also possess a breadth and depth of experience in providing HIV care and treatment services throughout the region. Oftentimes overlooked, the private sector is poised to play a larger role in filling gaps in HIV programming. Recent mapping exercises of private-sector resources for health in 4 Caribbean countries conducted by the Strengthening Health Outcomes through the Private Sector (SHOPS) project found that the private health sector was much larger than originally understood, and many private providers had training in HIV counseling, testing, or treatment but were not using their skills due to lack of patient demand.Private providers in the Eastern Caribbean are capable of playing a larger role in the HIV response.Our review of the literature has shown that transitions to country ownership, including some current PEPFAR transitions, face many barriers to success. Transitions have been hindered by donor-imposed timelines; the exclusion of key stakeholders in the planning process; lack of clear communication; and failure to ensure recipient countries have the resources and capacity to successfully maintain gains made under PEPFAR support. PEPFAR has been aiming to reverse this trend with a focus on country ownership in PEPFAR II and sustainability in PEPFAR 3.0. Our findings identified areas of overlap with the latest PEPFAR guidance and suggested additional points to consider for a successful transition.Specifically, PEPFAR’s most recent COP Guidance has incorporated a new assessment of sustainability. As a part of the assessment, country programs are asked to “define gaps and bottlenecks, structural and cultural barriers.”Our findings suggest that stakeholder engagement and clear communication are essential steps in a successful transition to country ownership. The new COP Guidance prioritizes stakeholder engagement and offers some insight on how to best engage private-sector stakeholders in program planning. Much of the guidance, however, places local stakeholders in a consultative role rather than prioritizing the primacy of the partner country in determining the way forward.PEPFAR transition guidance should clearly articulate the importance of meaningful involvement of local stakeholders in the transition process.A major challenge in conducting this review was navigating the changing vernacular and perceptions of transition to country ownership among stakeholders. Oftentimes “graduation,” “transition,” “country ownership,” “sustainability planning,” and “donor withdrawal” were used interchangeably. The need for broad search terms produced a volume of results that made an exhaustive literature search unfeasible. In the future, a more systematic review could be beneficial particularly as more articles are produced regarding PEPFAR’s transition to greater country ownership. The review also relied on the existence of available literature that conformed to the defined research questions. Given the limited availability of scientifically conducted research on the topic area, the majority of available literature was project reports.Lessons learned from past and current transitions from donor-led programs to country ownership suggest that the first step in any successful transition to country ownership is mutually agreeing upon the goal and actions required and then developing and articulating a detailed yet flexible roadmap, in collaboration with relevant stakeholders to ensure buy-in and ownership of the process. Assessing readiness for such transition is challenging and must account for unique contextual factors across all facets of the health system. In the Caribbean, readiness for transition will require strengthening health systems, further engaging the private sector, and building the capacity of NGOs to take on essential program functions. Ongoing donor support for targeted capacity-building technical assistance and long-term M&E will be vital to ensuring that the countries of the Caribbean are able to take a leading role in their HIV responses while maintaining or improving upon the substantial gains made with PEPFAR support.


Addressing this expansion is essential before control and prevention of dengue are implemented. An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services. Approximately 2.5–4 billion persons, 40%–60% of the world’s population, live in areas at risk for dengue virus (DENV) infection  and the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) (www.indepth-network.org) and held in Accra, Ghana, in February 2013 to consider key questions regarding dengue in Africa. Have we failed to observe an escalation of dengue in Africa causing a disease incidence of similar magnitude to that of Latin America, or is dengue truly not spreading into Africa for epidemiologic reasons that are not yet understood? The meeting addressed 4 major themes surrounding this central issue to advance our understanding of the epidemiology of dengue in Africa: 1) diagnostic tools and diagnostic capacity development; 2) improving estimates of the epidemiology and incidence of dengue; 3) biology of vectors and implications for vector control strategies; and 4) health policy, health services, and epidemic preparedness. The considerations and main suggestions for each theme are outlined in this report.An expert conference on Dengue in Africa was organized by the International Research Consortium on Dengue Risk Assessment, Management, and Surveillance (IDAMS) , is limited in Africa , along wImplementation of a tiered laboratory diagnostic system along these lines across Africa would facilitate unambiguous diagnosis of dengue infection in a subset of clinically suspected cases, provide quality assurance and quality control for feeder laboratories, and support a program of locally relevant scientific research. For example, 1 major step would be to evaluate these diagnostic tests in patients with AFI and take into account the high background endemicity of malaria and various co-circulating flaviviruses.Africa lacks systematic surveillance and reporting of many diseases, including dengue  in Africa, which are producing longitudinal demographic data about lives of persons in low-income and middle-income countries . These mAedes aegypti and Ae. albopictus mosquitoes) are present in Africa. In Senegal, other Aedes mosquito species have also been shown to be involved in transmission of sylvatic dengue (Should dengue be identified as imposing a major burden in Africa, it will be essential to understand the biology and behavior of local vectors because these factors will influence transmission, as well as selection and design of effective control tools and strategies. The 2 major DENV vectors (Ae. aegypti mosquitoes need to be distinguished in Africa: an ancestral forest or sylvan form, and a global domestic form. These 2 forms differ in distribution, behavior (Ae. aegypti mosquitoes in Africa (At least 2 forms of Ae. albopictus mosquitoes continue to spread through Africa since they were first reported in Nigeria in 1991, and these mosquitoes might play a major role in the epidemiology of dengue in Africa (Ae. albopictus mosquitoes blood-feeding on humans (Aedes spp. mosquitoes are diurnally active, which indicates that long-lasting insecticide-treated bed nets are ineffective for dengue vector control (Dengue vector control requires thorough knowledge of vector biology and behavior to be effective (,Given a lack of awareness of dengue in Africa, it is perhaps not surprising that dengue control is a low-priority health policy in this region (In summary, the expert conference in Accra highlighted 4 key action points. First, dengue diagnostic tools must be made more widely available in the health care setting in Africa. Second, representative data need to be collected across Africa to uncover the true incidence of dengue and more clearly define its transmission in the region. Third, established networks, such as African laboratory networks, the Pasteur International network, the INDEPTH network, and others, should collaborate to produce these needed types of data. Fourth, policy needs to be informed by improved information to take necessary steps for dengue vector control and provision of health services. Addressing these issues will be essential before any major future decisions regarding control or prevention of dengue in Africa can be made.


Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder (MDD), Parkinson’s disease (PD), schizophrenia, posttraumatic stress disorder (PTSD) and Alzheimer’s disease (AD). In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders. Brain disorders are associated with several symptom clusters as well as many neural dysfunctions. For example, although Parkinson’s disease (PD) is associated with reduced dopamine levels in the brain  and negative symptoms . Unlike other brain disorders, schizophrenia is often perceived to involve multiple and complex neural dysfunctions  allowing for dimensional assessment of hallucinations and delusions, Schneider et al. , who disFurther, although it was found depression and apathy are associated with different cognitive performances in PD  that produce fear responses triggered by subsequent exposures to reminders of the traumatic event . Additionally, AD is also associated with the formation of beta-amyloid plaques and neurofibrillary tangles in the cortex and hippocampal regions . For example, some studies found that some motor symptoms in PD correlate with each other, including hand movement, gait and speech  or based on frequency (low or high) or body part affected . As another example, language deficits have been reported in AD, and it is likely that subcategorizing language deficits into several components may help understand the neural and therapeutic aspects of each in isolation. Similarly, as reported above, few studies have subcategorized apraxia in AD into motor processes that involve either mimicking or pantomiming, and report that these involve differential neural mechanisms  investigate clinical profile of the different symptoms; (b) study whether any of these correlate and thus related; (c) test the effects of drugs on each symptom in isolation; (d) investigate the neural substrates of each symptom; and (e) design computational models to understand the neural mechanism of each symptom in isolation. For example, a model of a brain region  should be able to explain all symptoms associated with hippocampus dysfunction, including memory decline in dementia and delusions in schizophrenia.All 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.


Objective: The theory of deliberate practice has been applied to many skill-based performance activities. The primary aim of this project was to integrate synergistic principles from deliberate practice and consensus-derived competencies for interprofessional education into a framework upon which educational models to advance interprofessional experiential education (IEE) might be built.Methods: CINAHL, ERIC, and MEDLINE databases were searched using the keywords “deliberate practice” and “interprofessional education,” both individually and in combination. Relevant articles were selected from the catalog based on support for the premise of the project. Defining characteristics of deliberate practice were distilled with particular emphasis on their application to the Interprofessional Education Collaborative's (IPEC) core competencies. Recommendations for IEE development were identified through the synthesis of deliberate practice principles and IPEC competencies.Results: There is a high degree of synergy between deliberate practice principles and IPEC competencies. Our synthesis of the literature yielded a cyclical four-step process to advance IEE: (1) implement an IEE plan guided by the student's strengths/weaknesses and in consideration of the collaborative practice skills they wish to develop, (2) engage in IPE experiences that will challenge targeted skills according to the IEE plan, (3) embed frequent opportunities for student reflection and preceptor/team feedback within IEE plan, and (4) revise the IEE plan and the IPE experience based on insights gained during step 3.Conclusion: The cyclical four-step process synthesized through this literature review may be used to guide the development of new IEE models. The purposeful development of IEE models grounded in a theory that has already been operationalized in other skill-based performance areas is an important step to address expanding accreditation standards throughout the health professions mandating interprofessional education for pre-licensure health professional students. Interprofessional practice and education (IPE) has been identified as a mechanism capable of impacting the Triple Aim in healthcare; namely, improving the patient experience with care, improving the health of populations, and reducing the per capita cost of health care  core competencies expert panel report, on the skills required for interprofessional collaborative practice, we sought to identify a skill-based theoretical framework that might serve as a foundation to foster advancement of interprofessional experiential education (IEE). The theory of deliberate practice surfaced quickly in our cursory search, as it has been applied to the development of expertise in a wide array of skill-based disciplines, including chess, music, sports, and healthcare  core competencies. Recommendations for IEE development were identified through the synthesis of deliberate practice principles and IPEC competencies.The findings guiding our proposed framework were derived from a total of 37 articles and reports with 27 pertaining to deliberate practice and 10 discussing IPE. The key elements of deliberate practice identified across these 27 articles are best described in narrative form. The theory of deliberate practice emphasizes, in the pursuit of expertise, quality over quantity of experiences and values the student's holistic ability to process, and integrate improvements in targeted skills  process, rather than simply performing a task repetitively until mastered. To achieve maximal efficiency, time for self-reflection, and instantaneous feedback are vital for allowing the learner to self-adjust and make improvements before engaging in the next task. Mastery is thus achieved through repeated cycles of focused practice and self-editing, with each cycle emphasizing one or more aspects of a desired skill.With sufficient investment of time and dedication to the principles of deliberate practice, individuals can develop expertise in targeted areas Figure . HoweverThe IPEC competency framework includes 38 competencies dispersed across the following four domains: values/ethics for interprofessional practice (10 competencies), roles/responsibilities (9 competencies), interprofessional communication (8 competencies), and teams and teamwork (11 competencies) . SyntheValues/EthicsCompetency 7: Demonstrate high standards of ethical conduct and quality of care in one's contributions to team-based care.◦ Roles/ResponsibilitiesCompetency 5: Use the full scope of knowledge, skills, and abilities of available health professionals and healthcare workers to provide care that is safe, timely, efficient, effective, and equitable.◦ Competency 8: Engage in continuous professional and interprofessional development to enhance team performance.◦ Interprofessional CommunicationCompetency 4: Listen actively, and encourage ideas and opinions of other team members.◦ Competency 7: Recognize how one's own uniqueness, including experience level, expertise, culture, power, and hierarchy within the healthcare team, contributes to effective communication, conflict resolution, and positive interprofessional working relationships.◦ Teams and TeamworkCompetency 8: Reflect on individual and team performance for individual, as well as team, performance improvement.◦ Competency 11: Perform effectively on teams and in different team roles in a variety of settings.◦ Having identified synergistic competencies, the next step involved creating a process through which the student might begin developing competence in these areas during a clinical rotation. We propose a cyclical four-step process to achieve this aim: (1) implement an IEE plan guided by the student's strengths/weaknesses and in consideration of the collaborative practice skills they wish to develop, 2) engage in IPE experiences that will challenge targeted skills according to the IEE plan, 3) embed frequent opportunities for student reflection and preceptor/team feedback within IEE plan, and (4) revise the IEE plan and the IPE experience based on insights gained during step 3. A visual overview of this process is provided in Figure  engage i embed frThe four-step process identified through this literature review and synthesis may be used to guide the development of new models of interprofessional experiential education. The purposeful development of new IEE models rooted in an established theory that has already been applied to other skill-based performance areas is an important step to address looming accreditation mandates throughout the health professions.We believe that robust, meaningful IEE experiences require an intentional effort to design the educational experience in accordance with students' strengths/weaknesses and their specific learning goals. It is not enough to simply place a student on a team and expect them to develop competence in interprofessional practice. Principles of deliberate practice possess a high degree of synergy with IPE and, as we have attempted to demonstrate with this project, can be integrated into the interprofessional clinical learning environment as an educational framework upon which meaningful, intentional IEE experiences can be built. Our hope is that this framework will help clinical educators tailor their clinical rotations to best train students in interprofessional collaborative practice. The educational model proposed offers a mechanism through which preceptors might help their students begin to develop competence in this area through a proactive process; not only to observe the tasks of practitioners, but also to gain direct, customized experience to develop and continually refine critical skills that will help prepare them for team-based practice upon licensure. This model provides a pathway for activities to be tailored to fit each student's individual needs in order to maximize their professional development.Educators in medicine and nursing have already used deliberate practice to teach and train their students (Clapper and Kardong-Edgren, Quality patient care is increasingly dependent on collaborative teamwork. While general consensus and accreditation guidelines underscore the importance of interprofessional education, to our knowledge, no specific theoretical frameworks have been proposed to facilitate students' acquisition of the core competencies for collaborative practice outlined by the Interprofessional Education Collaborative. Motivated by the growing trend of integrating interprofessional education into health professional education, we attempted through this project to develop such a framework, which we believe clinical educators can use to help their students begin the process of developing interprofessional expertise. The model proposed herein integrates principles of deliberate practice with synergistic interprofessional practice competencies suitable for skill development in an experiential education setting. We encourage clinical educators preparing their students for interprofessional collaborative practice to utilize this framework and to study/disseminate educational outcomes from its use.JZ conceived, designed, and directed this study, and JW completed the literature review. Both authors analyzed and synthesized results. The proposed model and manuscript were developed collaboratively.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.


Ethylene is a gaseous plant hormone involved in many aspects of plant life, including seed germination, flower senescence, abscission, and fruit ripening , 1 to nodulation (Guinel), 1 to salt tolerance , and 1 to heavy metals ; 1 original article is related to Fe (iron) deficiency , and the other one to N (nitrogen) deficiency .This research topic updates recent results relating ethylene to different aspects of plant mineral nutrition. It includes 10 reviews and 2 original articles: 7 reviews are related to nutrient deficiencies  deficiency . This higher ethylene production is generally associated with increased transcript abundance for genes involved in ethylene biosynthesis and signaling . Moreover, the mitogen-activated protein kinases 3 and 6 (MPK3/MPK6), that can regulate ethylene production, increase under Fe deficiency  or under heavy metal stress . In the case of N, the relationship between its deficiency and ethylene production seems to be complex, affected by the degree of the deficiency and the plant genotype .Since nutrient deficiencies cause stress to plants and stress promotes ethylene synthesis . In the nodulation process, ethylene production increases early in the symbiosis (Guinel).Similarly to nutrient deficiencies, both salinity stress and heavy metal stress also cause higher ethylene production and increased transcription of ethylene biosynthesis and signaling genes , to salinity stress , and to heavy metal stress , while it is considered a negative regulator of the nodulation process (Guinel). Despite these generally accepted roles, conflicting results have also been reported. As examples, some research has shown that ethylene insensitive plants are more tolerant to salinity  or to heavy metal stress  than corresponding wild types. To explain these contradictory results, it should be taken into account the different experimental conditions used, including plant material, dosage, days of treatments, etc. . Additionally, it should be considered that excessive ethylene could inhibit plant growth and development .In general, ethylene plays positive roles in the activation of responses of plants to nutrient deficiencies , enhanced acid phosphatase activity under P deficiency (Song and Liu), upregulation of the HAK5 potassium transporter under K deficiency (Schachtman), development of root hairs under Fe, K, B (boron) or P deficiency , and development of cluster roots under Fe or P deficiency . In relation to salinity stress, ethylene has been implicated in the regulation of Na+/K+ homeostasis ; and in relation to heavy metal stress, in the network leading to glutathione and phytochelatin synthesis . In the nodulation process, ethylene has been implicated in most of the steps leading to a mature nodule and even in nodule senescence (Guinel).In relation to nutrient deficiencies, ethylene has been implicated in the activation of both physiological and morphological responses, such as enhanced ferric reductase activity under Fe deficiency  and P deficiency responses ; with ABA to regulate responses to salinity ; and with ROS to regulate responses to K deficiency (Schachtman) and heavy metals . On the other hand, Lucena et al. present evidence suggesting that ethylene regulates different responses to Fe deficiency through distinct transduction pathways, which is in agreement with recent proposals about ethylene signaling .The participation of ethylene in all the processes described above suggests it should act in conjunction with other signals, and/or perhaps through different transduction pathways, to confer specificity to the different responses. Both possibilities are reflected in the reviews included in this research topic. As examples, ethylene interacts with auxin and phloem signals to regulate Fe deficiency  and between salinity and nutrient deficiencies .Despite the specificity conferred by different signals, the common participation of ethylene in different processes related to plant mineral nutrition could partly explain the frequent cross talks among nutrient deficiency responses (In conclusion, this research topic, by putting together different nutritional aspects affected by ethylene, tries to pave the way for future research about the role of this simple but fascinating hormone on plant mineral nutrition.For the Editorial, AS reviewed the works about P and K; RP reviewed the works about N and B; and FR reviewed the rest of works. A draft of the Editorial was first written by Dr. Romera and then Dr. Smith and Dr. Pérez-Vicente revised and modified it to get the final version.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.


High blood pressure is common during the acute phase of stroke and is associated with a poor outcome. However, the management of high blood pressure remains unclear. The ‘Efficacy of Nitric Oxide in Stroke’ trial tested whether transdermal glyceryl trinitrate, a nitric oxide donor that lowers blood pressure, is safe and effective in improving outcome after acute stroke. Efficacy of Nitric Oxide in Stroke is an international multicenter, prospective, randomized, single-blind, blinded endpoint trial, with funding from the UK Medical Research Council. Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140–220 mmHg were randomized to glyceryl trinitrate or no glyceryl trinitrate and, where relevant, to continue or stop prestroke antihypertensive therapy. The primary outcome is shift in modified Rankin Scale at three-months. Patients or relatives gave written informed (proxy) consent, and all sites had research ethics approval. Analyses will be done by intention to treat. This paper and attachment describe the trial's statistical analysis plan, developed prior to unblinding of date. The statistical analysis plan contains design and methods for analyses, and unpopulated tables and figures for the two primary publications and some secondary publications. The database will be locked in late February 2014 in preparation for presentation of the results in May 2014. The data from the trial will improve the precision of the estimates of the overall treatment effects (efficacy and safety) of results from completed trials of blood pressure management in acute stroke, and provide the first large-scale randomized evidence on transdermal glyceryl trinitrate, and of continuing (vs. stopping) prestroke antihypertensive medications, in acute stroke. High blood pressure (BP) is present in 70% or more of patients with acute ischemic stroke and intracerebral hemorrhage (ICH) Nitric oxide (NO) donors are candidate treatments for acute stroke: NO is a cerebral and systemic vasodilator, modulates vascular and neuronal function, and inhibits apoptosis Preclinical studies of cerebral ischemia found that NO donors reduce stroke lesion size and improve regional cerebral blood flow (CBF) and functional outcome Intravenous sodium nitroprusside reduced BP without altering CBF and exhibited antiplatelet effects (thereby precluding its use in ICH) On the basis of these preclinical and clinical data showing feasibility, tolerability and apparent safety of GTN, and the potential for efficacy, the large ‘Efficacy of Nitric Oxide in Stroke’ (ENOS) trial was started and is ongoing. ENOS is assessing, in a partial, factorial, prospective, randomized, single-blind, blinded-outcome design, whether to lower BP with GTN (vs. no GTN) and whether to continue (vs. stop) prestroke antihypertensive therapy. The trial commenced in 2001, and protocols for the main trial and an outline on the management of neuroimaging were published in 2006 and 2007, respectively EME Journal, part of the National Institute for Health research collection of peer-reviewed open access journals.Prior to presentation of the primary analyses in 2014, two further publications are planned, the statistical analysis plan (SAP) and a detailed listing of baseline characteristics. The accompanying Supporting Information Appendix S1 details the SAP and is presented prior to locking of the trial database (expected in late February) so that analyses are not data driven or selectively reported Importantly, the ENOS Trial Steering Committee have changed the original plan for the analysis of the primary outcome, as reported in the protocol (published in IJS) In the future, data from ENOS will be integrated into individual patient data meta-analyses of NO donors, and BP lowering, for acute stroke (the latter through the ‘Blood pressure in Acute Stroke Collaboration’), and made available to participating countries and the ‘Virtual International Stroke Trials Archive’ Ultimately, a subset of the data will be made available over the web, as with the International Stroke Trial