An effective capacity building process for healthcare workers is required for the delivery of quality health care services. Work-based training can be applied for the capacity building of health care workers while causing minimum disruption to service delivery within health facilities. In 2012, clinical mentoring was introduced into the Jigawa State Health System through collaboration between the Jigawa State Ministry of Health and the Partnership for Transforming Health Systems Phase 2 (PATHS2). This study evaluates the perceptions of different stakeholders about clinical mentoring as a strategy for improving maternal, newborn and child health service delivery in Jigawa State, northern Nigeria.Interviews were conducted in February 2013 with different stakeholders within Jigawa State in Northern Nigeria. There were semi-structured interviews with 33 mentored health care workers as well as the health facility departmental heads for Obstetrics and Pediatrics in the selected clinical mentoring health facilities. In-depth interviews were also conducted with the clinical mentors and two senior government health officials working within the Jigawa State Ministry of Health. The qualitative data were audio-recorded; transcribed and thematically analysed.The study findings suggest that clinical mentoring improved service delivery within the clinical mentoring health facilities. Significant improvements in the professional capacity of mentored health workers were observed by clinical mentors, heads of departments and the mentored health workers. Best practices were introduced with the support of the clinical mentors such as appropriate baseline investigations for pediatric patients, the use of magnesium sulphate and misoprostol for the management of eclampsia and post-partum hemorrhage respectively. Government health officials indicate that clinical mentoring has led to more emphasis on the need for the provision of better quality health services.Stakeholders report that the introduction of clinical mentoring into the Jigawa State health system gave rise to an improved capacity of the mentored health care workers to deliver better quality maternal, newborn and child health services. It is anticipated that with a scale up of clinical mentoring, health outcomes will also significantly improve across northern Nigeria. Increasing the number of skilled health workers to provide quality health services is a key health systems strengthening objective . Within classroom training [Within clinical practice in particular, work based training is a key part of professional development which has the capacity to develop health care workers in ways quite different from, but complementary to formal training . The keytraining ,9. Clinitraining ,11. Clintraining . A typictraining .Nigeria has an estimated population of over 140 million people . Howevercontinuous professional capacity development to effectively provide the right quality of healthcare services to improve maternal, newborn and child health outcomes. It was hypothesized that the implementation of clinical mentoring would assist in addressing the prevailing challenges to maternal, newborn and child healthcare service delivery within northern Nigeria. The objective of this study was to elicit the perceptions of stakeholders about clinical mentoring and its potential for improving maternal, newborn and child health service delivery within Jigawa State in northern Nigeria. The study highlights some successes as well as some challenges associated with the implementation of clinical mentoring within the context of the Jigawa State health care system.There is considerable evidence that work-based training approaches such as clinical mentoring has been successfully utilized to transfer knowledge and skills in several fields such as management of HIV/AIDS , neonataJigawa State is within the north western part of Nigeria and consists of 27 Local Government Areas . Accordiwere randomly selected and recruited to participate in clinical mentoring from different cadres of health workers that routinely work in the five selected health facilities in Jigawa State  health workers to be mentored were recruited through purposive sampling from tertiary health facilities i.e. the teaching hospitals and were allowed to travel from their places of primary assignment to the clinical mentoring health facilities. The clinical mentoring intervention involves collaboration between the Jigawa State Ministry of Health  and the Partnership for Transforming Health Systems Phase 2 (PATHS2) which provides support for the allowances of the clinical mentors. PATHS2 is a health systems strengthening project sponsored by United Kingdom’s Department for International Development (DFID) and implemented by a consortium of partners led by Abt Associates. PATHS2 works in collaboration with the Government of Nigeria  and other stakeholders to improve the planning, financing and delivery of sustainable health services to Nigerians.The clinical mentors were identified through the professional network of PATHS2’s consultant on clinical mentoring. The clinical mentors work full time at teaching hospitals in the surrounding States of Kano and Bauchi States. These clinical mentors Each of the different subgroups of study participants  were identified as stakeholders in the implementation of clinical mentoring and regarded as key informants for the study. In February 2013, interviews by the study team (led by the first two authors of this paper) were conducted with the stakeholders of the clinical mentoring intervention in Jigawa State. The interviews were documented using tape recorders. The qualitative data were transcribed, a pre-determined coding framework was applied and subsequently thematic analyses of the data were undertaken. Members of the study team who were involved during the data collection process also provided assistance in identifying relevant themes. Regular meetings were held by the study team in order to reach consensus on the interpretation of the data collected during the interviews.A qualitative approach was adopted for this study so as to provide detailed information and sufficiently elicit the opinions, experiences as well as perceptions of the different stakeholders with respect to the clinical mentoring intervention as opposed to a quantitative approach. The expectation of the study team was that any connections or contradictions between activities and perceived changes arising from the implementation of clinical mentoring will be adequately highlighted using a largely qualitative methodology.or otherwise of the clinical mentoring intervention within the context of the State-wide health system. The Jigawa State Government health officials were asked questions about the most challenging areas within the Jigawa State health system and how clinical mentoring has helped to address these challenges. Other questions were intended to assess the key lessons learnt, best practices, specific improvements that have been recorded as well as recommendations to improve the implementation of clinical mentoring within the State. The study team also organized structured interviews with the mentored health workers. The structured interviews included questions on the perceived effect/impact of clinical mentoring on health facility activities  were carried out using semi-structured interview guides to elicit their opinions and experiences vis-à-vis the implementation of clinical mentoring within the intervention health facilities. The interview questions for the departmental in-charges sought to obtain information about the activities carried out by the clinical mentors during their visits, benefits of clinical mentoring to the health facility and any improvements observed due to the implementation of clinical mentoring within the intervention health facilities. There were also in-depth interviews with Jigawa State Government health officials to get their perspectives on the effectiveness Ethical clearance for the study was obtained from the Jigawa State Ministry of Health. In addition, informed consent was obtained from all the study respondents before the interviews commenced. The verbal consent of the study respondents were documented using tape recorders. The objective of the study, respondents’ right to refuse participation and freedom to terminate participation in the study at any time was discussed with each study participant. Study respondents were assured of the confidentiality of their responses.i.Inadequate numbers and capacity of the health workforce to provide adequate health care services to the State’s population.ii.Lack of skilled health care professionals and inadequate training of the health workers within the State.iii.Attrition of key healthcare workers, including doctors and midwives.Two senior level healthcare officials of the Jigawa State Ministry of Health were interviewed as part of the evaluation of the clinical mentoring intervention within selected health facilities in Jigawa State. Government officials acknowledge that the human resources for health system within the State have multifarious challenges, including but not limited to the following:“…perhaps a key outcome of the implementation of clinical mentoring will be that Jigawa State better understands other ways to tackle the human resources for health situation and improve healthcare service delivery.”With the introduction of clinical mentoring visits, some of these challenges are being addressed as there appears to be an increase in the number of better trained health professionals providing health services to patients. These improved professional healthcare services have been provided through the expertise and contributions of the clinical mentors. The Gunduma Health System officials indicated that one of the key lessons learnt from the implementation of the clinical mentoring programme was the increased focus the mentoring visits have given to maternal, newborn and child health issues within the health care delivery system of the State. It was also reported that the clinical mentoring intervention has increased awareness about the need to explore other innovative approaches/strategies to address the critical health workers’ situation within Jigawa State. A Gunduma health official remarked:Highlighting some challenges however, the Gunduma healthcare officials pointed out that the current approach whereby the clinical mentors visit health facilities, provide services and travel back on the same day naturally limits the time spent providing services and this invariably affects the quality of healthcare services provided. The financial implication of retaining and recruiting more clinical mentors is also a serious challenge and Jigawa State needs to make adequate budgetary allocations to address this challenge.“The main suggestion I have is on integrating clinical mentoring into the district health system within the State so that it works through an existing system.”The key suggestion from the Gunduma health systems officials is that clinical mentoring needs to be effectively integrated into the existing district health system within the State. This integration it was argued would ensure sustainability, greater ownership by the State government and could potentially give rise to more benefits to the State’s health system. In connection with this suggestion, a Gunduma health official remarked:It was proposed that adequate temporary accommodation should be provided to enable clinical mentors to follow up on some cases as maybe appropriate. It was also argued that with the perceived increase in patient flow within the mentoring health centres, clinical mentors should spend more visiting hours and days providing services within their assigned health facilities or more clinical mentors should be recruited. Jigawa State needs to have a long term plan of developing a pool of consultants to sustain the clinical mentoring programme.“…my capacity has been built and I have gained in experience.”Thirty three (33) mentored health workers recruited across the five selected health facilities were interviewed as part of the study. Table “We as mentors have introduced clinical protocols to guide the health workers in the conduct of their work e.g. protocols for magnesium sulphate, management of post-partum hemorrhage, and the management of the third stage of labour…”The three obstetrics clinical mentors recruited into the clinical mentoring intervention were interviewed as part of the study. The obstetrics clinical mentors indicated that the preliminary assessment which was carried out at the start of the clinical mentoring intervention provided guidance and thus assisted in identifying weaknesses as well as specific areas for improvement among health workers working within the obstetrics department. Significant changes arising from the clinical mentoring intervention include updated treatment guidelines on basic emergency obstetric health care, pre-eclampsia and eclampsia, post-partum hemorrhage as well as the management of the third stage of labour. An obstetrics clinical mentor remarked:Clinical mentors report that as a result of the mentoring visits, infection prevention practices have been introduced into the health facilities where they visit. Such emphasis on infection prevention will tend to minimize the possibility of patients picking up ‘hospital-based infections’ while visiting the clinical mentoring health facilities.“In health facilities in which we visit, we have developed and introduced treatment protocols, some of which are on the notice boards in some wards…”The three pediatrics clinical mentors participated in interviews as part of the evaluation of the clinical mentoring intervention. The pediatrics clinical mentors indicated that standard treatment guidelines for the management of different pediatric cases have been introduced following the mentoring visits. A pediatric clinical mentor enthused:“We have introduced the use of nasogastric (NG) tubes for feeding pediatric patients with severe malnutrition”.There are other significant changes attributable to clinical mentoring as highlighted by a pediatric clinical mentor:“The practice of weighing pediatric patients during each visit which was not the case before the start of the clinical mentoring intervention has also been introduced”.Another pediatric clinical mentor pointed out:“We have made significant efforts within the mentoring centers to ensure that weighing scales were acquired for use within the pediatrics department”.This approach of measuring pediatric patients during each visit has most likely given rise to the appropriate calculation of dosages for pediatric patients in addition to effective growth monitoring as part of best practices towards managing pediatric cases. A pediatric clinical mentor indicated:“A good part of the mentoring visits for me is seeing the improvement in the mentee’s knowledge, skills and confidence…”Greater emphasis has also been placed on better record keeping by the health care workers. Alluding to the changes arising from the mentoring visits, a pediatrics clinical mentor remarked:to assign one mentor to cover a health facility and not one mentor covering more than one health facility as is currently the case. This will ensure that the clinical mentor concentrates on the cases and health workers to be mentored in just one assigned health facility. Another suggestion was that temporary accommodation should be provided for the clinical mentors to allow the mentors follow up on cases when and where necessary. The current set-up whereby mentors travel from their primary location, provide services and have to travel back the same day limits the quality and quantity of care provided to patients. It is also not advantageous to the patients who may need further monitoring such as those that have had surgeries.As a way to improve the effectiveness of clinical mentoring, a clinical mentor suggested that it would be more appropriate “There is need to create more opportunities and sensitize community leaders in the surrounding communities while also liaising with the health facility in-charges to assist in mobilizing community members so as to better utilize the expertise and services offered by the clinical mentors.”It was proposed that payment incentives could be introduced to increase the motivation of the clinical mentors. Furthermore, it was recommended that the benefits of the mentoring visits should be extended beyond the health workers in the mentoring centres, such that health workers working in surrounding health facilities could be invited on the days that the consultants visit to learn alongside the health workers in the mentoring centres. In addition, there should be proper community mobilization such that the communities within the catchment areas of the health facilities should be enlightened about the visit of the consultants to ensure that a larger proportion of community members access and utilize the services of the visiting consultants. A clinical mentor remarked:“The clinical mentors are responsible for the introduction of the use of magnesium sulphate as the standard treatment for pre-eclampsia and eclampsia within the intervention health facilities.”Healthcare workers in-charge of obstetrics in each of the five intervention health facilities took part in interviews as part of the evaluation of the implementation of clinical mentoring. Healthcare workers in-charge of obstetrics indicated that clinical mentors have introduced new skills and updated the knowledge of the mentored health workers working in obstetrics:“There is an improvement in the management of post-partum hemorrhage as mentored health workers were trained on the proper use of misoprostol”.In addition, a health worker in-charge of obstetrics in one of the intervention health facilities indicated:“Proper record keeping and improved charting of medications have also been observed…”Another health worker in-charge of obstetrics pointed out:“Caesarean section (C/S) deliveries are more likely to be routinely carried out for some pregnancies especially when there are abnormal conditions that complicate normal vaginal delivery”.The health facility departmental in-charges mentioned that health workers appear more confident when handling cases and this was reflected in comments from a health facility departmental in-charge:“The clinical mentor is assisting the health facility in addressing high burdens of anaemia and malaria in pregnancy within the communities that utilize the services of the health facility”The obstetrics departments of the intervention health facilities suggest an increase in patient flow as well as a decrease in the number of referrals out of the health facility to higher level health facilities. An in-charge of obstetrics in one of the intervention health facilities pointed out:“We now record the expected due date (EDD) for prospective mothers as part of best practices for effective maternal healthcare…and to help us with this the clinical mentor came with a calendar so that the EDD for clients can be easily calculated.”An obstetrics unit head within an intervention health facility also indicated:“More patients are coming…a health worker at a nearby health facility referred a patient and insisted that the patient visits on the day the clinical mentor visits this health facility…”The health workers in-charges of pediatrics department in each of the five clinical mentoring intervention health facilities were interviewed as part of the study. The health workers in-charge of pediatrics concur with the mentored health workers and suggest that there has been an increase in pediatric patients coming to access health services. It was implied by health workers in-charge of pediatrics that the mentored health workers tend to better manage patients, thus likely reducing the number of pediatric cases referred out of the health facilities. A pediatrics unit in-charge remarked:“The clinical mentor introduced the use of ambu-bags and these have been particularly useful for neonatal resuscitation and reducing neonatal mortality”.Aligning with the responses from the pediatric clinical mentors, pediatric unit in-charges indicate that some notable best practices have been introduced by the clinical mentors; for e.g. weighing pediatric patients which is crucial for the appropriate calculation of pediatric dosages as well as for growth monitoring. An in-charge of pediatrics in one of the intervention health facilities also pointed out:“There have been some changes in the treatment protocols for e.g. malnutrition; we have been taught that we should be careful with the use of IV fluids and instead insert NG-tubes especially for severely malnourished pediatric patients.”Proper baseline investigations and tests are now more likely to be carried out as part of standard management of pediatric cases following the introduction of clinical mentoring. The pediatrics clinical mentors also introduced changes to the management of malnutrition such as the use of nasogastric (NG) tubes for managing malnourished children within the intervention health facilities. A health worker in-charge of the pediatrics remarked:“Clinical mentoring has introduced new clinical approaches…resulting in improved standards of health care for our pediatric patients.”With the accessibility of the consultant pediatricians to health workers working in the intervention health facilities, it was reported that health workers tend to better manage clinical cases and if there is need, the clinical mentors could be contacted using a mobile telephone and thus the necessary guidance can be provided. This perception of an improved standard of pediatric care within the intervention health facilities was summarized by a health worker in-charge of pediatrics in one of the intervention health facilities as follows:This study set out to investigate stakeholders’ perceptions of clinical mentoring as an innovation for improving maternal, newborn and child health service delivery within Jigawa State in northern Nigeria. The study explored the implementation of clinical mentoring from four unique perspectives: clinical mentors, mentored health workers, departmental in-charges of Pediatrics and Obstetrics within intervention health facilities as well as government officials from the Gunduma Health Board. Utilizing a qualitative study design, the study elicits the responses of key actors in the implementation of the clinical mentoring intervention, discusses the implications for improving health care service delivery and outlines some key policy recommendations.Poor performance among health workers is usually associated with the lack of adequate knowledge and skills . Howeverduring each visit to ensure the appropriate calculation of pediatric dosages, appropriate baseline investigations for pediatric patients as well as the use of ambu-bags for neonatal resuscitation to reduce neonatal mortality.The preliminary assessments conducted at the start of the clinical mentoring intervention provided useful pointers on specific areas to focus on during the capacity building process. The vast majority of mentored health workers suggest that clinical mentoring did not only strengthen health workers capacity but it also appears to have improved service delivery and health facility management within the intervention health facilities. The contributions of clinical mentoring to health facility management and service delivery were also reiterated by the healthcare workers in charge of both Pediatrics and Obstetrics: clinical mentors have utilized their expertise to update the knowledge and skills of mentored health workers. More importantly, best practices were introduced and are being institutionalized with the support of the clinical mentors such as the use of magnesium sulphate for eclampsia management, misoprostol for the management of post-partum hemorrhage, weighing pediatric patients However serious considerations should be paid to the recommendations proposed by the clinical mentors such as the provision of temporary accommodation to allow the mentors follow up on cases when and where necessary. As a solution, the government can provide some form of “doctors’ lodge” to provide overnight accommodation for the clinical mentors to address the challenge of temporary accommodation. Pay for performance incentives can also be introduced to further motivate the clinical mentors which will have direct consequences on the quality of services provided at the health facilities. Criteria for computing these financial incentives could be based for example on the number of complicated cases managed per week or month over and above a set target. Concerted efforts should also be invested to ensure that the benefits of the mentoring visits are fully exploited by the catchment populations of the intervention health facilities through employing effective community mobilization strategies. Community mobilization could involve the use of meetings in surrounding communities that utilize the services of the health facilities as well as the mass media such as radio to inform communities about the availability of expert healthcare in the clinical mentoring health facilities. The availability of more patients through community mobilization could lead to better mentoring because of the exposure of the mentees to a wider variety of clinical cases. In addition, increasing access to the expertise of the clinical mentors by providing mentoring opportunities for the majority of health workers working within as well as others working outside the current mentoring centers should be a priority.Another obvious recommendation is the scale up of clinical mentoring to health facilities outside the current mentoring centers. In carrying out such a scale up to other health facilities, careful consideration should be paid to a more holistic system strengthening approach to the health system including the provision of essential drugs, adequate financial resource mobilization and reliable health information systems in addition to proper governance and accountability mechanisms. This is important because as implied elsewhere , simply This study has some key limitations: there is the possibility of response bias particularly among the mentored healthcare workers and clinical mentors. In addition the study design excluded health workers not participating in this clinical mentoring approach but working within the intervention health facilities, who may have provided an entirely different perspective. Furthermore, since the study was conducted just about six months after clinical mentoring commenced, there is lack of evidence on the longer term impact of clinical mentoring on health workers’ capacity and healthcare service delivery.This study suggests that the introduction of clinical mentoring into the Jigawa State health system has given rise to mentored health care workers with improved capacity to deliver better quality maternal, newborn and child health services. There is strong optimism that consequently there will be more emphasis placed on the need for and the provision of better maternal, newborn and child healthcare (MNCH) services. However this optimism needs to be matched with organizational support from the health facilities’ management as well as managerial support from the State’s Ministry of Health to improve health workers’ motivation, service delivery and health outcomes. Finally as suggested by healthcare officials working in the Gunduma Health Board, integrating clinical mentoring into the existing district health system within the State will promote ownership by the Government as well as the sustainability of clinical mentoring within the Jigawa State health system.


Application of pharmacogenetic knowledge with the help of quick and cheap companion diagnostics in the primary care setting is expected to deliver improved treatment and reduced heathcare costs. Warfarin and aspirin are the two most widely prescribed drugs for preventing cardiovascular diseases. Long term aspirin use has also been shown to reduce risk, recurrence and mortality from colorectal cancer. However, they both have narrow therapeutic windows and several genetic polymorphisms have been noted to influence their dose and efficacy. We therefore have launched two collaborative projects: first, to study the genetics of warfarin safety in the Gujarati Indian population and second, to identify further polymorphisms that modulates aspirin’s colorectal cancer chemopreventive efficacy. Understanding the impact of polymorphisms on dose and efficacy for these drugs would lead to development of a combined panel of markers that would predict accurate therapeutic dose with minimal risk for adverse reactions. These markers will be deployed at the point of care settings using a novel handheld genotyping device which will use disposable microfluidic cassettes and silicon nanowires currently developed by QuantuMDx. Results, future work, opportunities and barriers will be examined.The increase in identification of putative biomarkers and opportunities to develop tailored treatments are due to emergence of


Hepatocellular carcinoma (HCC) is a malignant tumor with hepatocellular differentiation and one of the most common cancers in the world. This type of cancer is often diagnosed when the survival time is measured in months causing high death rates . For theWe enhanced the classification process presented in  by incluThe results of classification experiment are summarized in The combination of nuclear, trabecular, and other tissue features enables improved classification rate in HCC detection using SVM. Even though the image characteristics are different in biopsy and surgically resected samples, the same classification system gives good performance in both samples. The HCC classification scheme introduced in this paper is implemented in the prototype “feature measurement software for liver biopsy,” and the probability of HCC is visualized for every ROI in the WSI. It will support pathologists in the HCC diagnosis along with the quantitative measurements of tissue morphology.


Size Principle of motoneuron recruitment stated that for any net excitatory input to the motoneuron pool, motoneurons were recruited in an orderly fashion, always from small to large. Stein and coworkers demonstrated that the size principle generalized to voluntary isometric contractions in humans, which they called Orderly Recruitment  and contractile properties of the associated muscle units. Considering the range of motoneuron and corresponding muscle unit properties, the obvious question arose about how and which motoneurons were selected by the central nervous system for various types of contractions and movements. Elwood Henneman and his coworkers proposed an unequivocal simple pattern in a series of papers starting in 1957 from experiments conducted on reduced cat preparations  muscles. Likewise, an anatomically defined motoneuron pool may under certain conditions be compartmentalized into task groups (Riek and Bawa, What do orderly recruitment and selective recruitment really mean? The accepted narrative is that orderly recruitment of motor units from small to large twitch force, results in a more precise control of force and movement; this precision is more important for small and mid range forces. By maintaining the same order of recruitment, the central nervous system minimizes the computational load across a wide range of desired outputs (Henneman et al., Another factor that has contributed to a misunderstanding of the orderly recruitment is the expectation for precise rank ordered recruitment (Henneman et al., laboratory conditions with simple muscles and a limited set of contractions, recruitment is orderly in terms of force (Milner-Brown et al., size principle of orderly recruitment will generalize to movements of everyday life.The ultimate meaning of recruitment order lies in the force output of the entire musculoskeletal system for the purpose of behaviorally relevant movements. Clearly in 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.


PLOS Biology Editors and the splicing does not affect the authors’ conclusions.The authors would like to clarify the source of splice lines that can be detected in several figures where lanes from parts of the same gel were juxtaposed. To assure readers of the integrity of the data and demonstrate the source and relationship of the gel lanes, we present in S1 Raw Data(PDF)Click here for additional data file.


In the past decade, remarkable change in malaria control and transmission has been documented in many  African nations and some countries are moving toward elimination. The malaria control community has long measured and tracked malaria transmission using a variety of methods from the highest to the lowest transmission areas. For program action across the spectrum of transmission between humans and mosquitoes, the balance between accurate measurement, sufficient detail to inform program decisions, and ease and simplicity of information collection, analysis and interpretation has always been challenging. A summary of historic and current efforts to measure parasites within and moving between people and mosquitoes will be provided with an emphasis on how the approaches and emphasis change as transmission intensity changes. The program decision needs for routine systems and for special studies to track transmission reduction will be discussed. The detection and verification of “zero” infection and transmission will be discussed in terms of tools and sampling methods that will allow the designation of malaria-free areas.


While historically viewed as an immune-privileged area fully isolated from the immune system, the central nervous system (CNS) is now appreciated to maintain dynamic bi-directional communication with the immune system across the blood–brain barrier (BBB) , 2. In nIt is now accepted that there is a need for constant immune surveillance of the adult CNS as part of normal host defense, acknowledging that simultaneous mechanisms must keep local CNS inflammation strongly in check . Indeed,Streptococcus pneumoniae is an important pathogen because it is the main cause of both community-acquired pneumonia and meningitis induced by a bacterial pathogen in otherwise healthy older children and adults. Much has also been learned about host immune responses elicited by pneumococcal pneumonia or meningitis using mouse models  is an arenavirus to which both mice and humans are susceptible and that causes varying combinations of visceral  and/or CNS  involvement in adult hosts. Murine LCMV infection has served as a prototype experimental system to study immunity to viruses for many years . This paThe host responses provoked by these two naturally occurring pathogens are used here to compare how the immune system recognizes and responds to the same challenge in the periphery and the CNS Table . The avaBoth the afferent and efferent arms of the immune system are efficiently activated in the context of either pneumococcal or LCMV infection, and the kinetics, magnitude, and composition of immune responses elicited in adult hosts appear remarkably similar when either a visceral organ or the CNS is the main target of disease Table . Acute CThe 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.


Emergency contraception pills (ECP) are among the 13 essential commodities in the framework for action established by the UN Commission on Life-Saving Commodities for Women and Children. Despite having been on the market for nearly 20 years, a number of barriers still limit women's access to ECP in low- and middle-income countries (LMIC) including limited consumer knowledge and poor availability. This paper reports the results of a review to synthesise the current evidence on service delivery strategies to improve access to ECP.A narrative synthesis methodology was used to examine peer reviewed research literature (2003 to 2013) from diverse methodological traditions to provide critical insights into strategies to improve access from a service delivery perspective. The studies were appraised using established scoring systems and the findings of included papers thematically analysed and patterns mapped across all findings using concept mapping.Ten papers were included in the review. Despite limited research of adequate quality, promising strategies to improve access were identified including: advance provision of ECP; task shifting and sharing; intersectoral collaboration for sexual assault; m-health for information provision; and scale up through national family planning programs.There are a number of gaps in the research concerning service delivery and ECP in LMIC. These include a lack of knowledge concerning private/commercial sector contributions to improving access, the needs of vulnerable groups of women, approaches to enhancing intersectoral collaboration, evidence for social marketing models and investment cases for ECP. Universal access to sexual and reproductive health and rights is an essential component of a healthy society. There are 222 million women in the world who wish to prevent pregnancy but are not using effective, modern methods of contraception. This results in an estimated 86 million unplanned pregnancies, 33 million unplanned births Strengthening service delivery and demand generation are key strategies to achieving universal access to sexual and reproductive health (SRH), including access to Emergency Contraceptive Pills (ECP). ECP is included in the list of 13 essential commodities in the framework for action established by the UN Commission on Life-Saving Commodities for Women and Children (UNCoLS) Quality service delivery at primary health care level, in both public and non-state sectors, is dependent upon inputs into the health system including supportive policies, evidence-based guidelines, trained workforce, secure contraceptive procurement and supplies, and financing. Ensuring the availability and access to quality health services is one of the main functions of a health system In order to improve the service delivery of ECP, leaders in LMICs require evidence to inform country efforts to strengthen quality assurance mechanisms, build the capacity of the pharmacy/drug-selling sectors to provide high-quality service and advice, co-ordinate and scale-up service provision, and generate demand through interventions such as social marketing. Improving service delivery requires building the knowledge base at country level. However, there is a paucity of such knowledge, nor is there a synthesis of quality evidence from a number of nations available to decision-makers in their efforts to increase access to ECP.In order to provide evidence to contribute to strengthening ECP delivery channels and developing policy guidance and tools to expand access to ECP including among vulnerable groups, we undertook a narrative synthesis of current research. The aim of this review was to identify what service delivery opportunities and interventions in LMIC can facilitate increased access to ECP. The results of this review and related reviews into consumer and service provider experiences will provide evidence to assist the ECP Technical Reference Team that has been established to help carry forward the UNCoLS recommendations at the global and national levels A narrative synthesis methodology was employed to analyse selected literature. This method was chosen due to the range of qualitative and quantitative methodologies of the studies identified for the review, which did not allow the pooling of results that are achieved in other systematic approaches to synthesising evidence such as statistical meta-analysis The scoping exercise identified databases and website where ECP literature could be retrieved and potentially useful keywords identified. Seven bibliographic databases , meta-Indexes ; websites of relevant organizations ; Google Scholar and the reference lists of key papers were searched to retrieve research literature.A Population, Interventions, Comparators, Outcomes, Study design (PICOS) question was formed to guide this review as per guidelines Observational studies, quasi experimental and non-experimental descriptive studies were considered suitable for inclusion and a systematic search of the contemporaneous primary research literature published from 2003 to 2013 in English in LMIC was undertaken. Electronic databases and the internet were searched using Medical subject headings (MeSH) . The following terms were employed: ‘Postcoital Contraception’ and ’Health Services Accessibility’ and ‘Healthcare Delivery’ and ‘Contraceptive Distribution’ and ‘Developing Countries’ and supplemented by the terms key words ‘emergency contraception,’ or ‘emergency contraceptive pills’ using the MESH terms, abstract and keyword options. This was modified as returns were poor. For example a search of ProQuest Health & Medical Complete  AND MeSH  AND MeSH  AND MESH (Contraceptive Distribution) AND MeSH (Developing Countries) AND ab((emergency contraception OR emergency contraceptive pills))returned no results. Searches that returned results are outlined in Retrieved records were first screened for their focus as per the PICOS question by the first author and duplicates removed. Discursive papers (papers without research data), those older than 10 years or whose focus was outside of the aim were removed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to report the review process Sixteen papers were identified as relevant in discussion with all authors. These papers were appraised by all authors using the Critical Appraisal Skills Programme (CASP) tool, a checklist developed for assessing the quality of qualitative evidence for use in policy and practice Six items were discarded: reviews that did not include primary data A narrative synthesis approach was conducted as per guidelines Ten documents were included in this study see . Five doECP service delivery to survivors of sexual assault was examined in four studies The study by Khan et al. also examined ECP service provision at police stations in India and Bangladesh and also found a lack of consistent protocols and low police knowledge of ECP An intervention study involving 20 purposefully selected police stations in urban and peri-urban study sites in Zambia demonstrated promising results of stocking ECP at police stations and training police officers to deliver ECP to eligible survivors of sexual violence and high rates of referral of women to health facilities Scaling up and mainstreaming ECP in national programs was the focus of three studies All three studies included provider training activities that were found to have improved knowledge. In Ethiopia Task shifting and sharing was the key focus of one intervention study from India that investigated the difference between ECP service provision by paraprofessionals  and physicians One intervention study in the review is concerned with examining the effectiveness of providing ECP to women on demand compared with in advance in Bangladesh Print and electronic media were used to communicate messages about ECP in studies included in the review. In Nepal an ECP brochure was developed for clients that were found to have been widely shared in the community This review has identified limited knowledge concerning service delivery interventions in LMIC that can facilitate increased access to ECP. Data showing the effects of interventions on reproductive health outcomes The findings of four descriptive studies included in the review indicate that considerable gaps exist in terms of service provision to survivors of sexual assault and rape. Despite one promising study more research is needed to determine how police and health workers can best collaborate to ensure survivors of sexual violence are treated with empathy and dignity and scale up the efficient quality care they require. Task shifting and sharing with cadres other than doctors was found to be a useful strategy to improve ECP access in four of the included studies, forming the focus of one study intervention More research is needed to better understand how mobile phone technologies and other forms of electronic communication can be used to disseminate ECP information and respond to consumers' questions and how this can be integrated with other social marketing and education interventions.There appears to be a dearth of comprehensive evidence of scale up and mainstreaming of ECP as only three studies were identified, none of which included evidence about all sectors that provide ECP. Evidence of workforce interventions is scarce particularly in terms of the types of workforce support and performance management initiatives that may be required across both the public and private sectors. This review highlighted that there is a paucity of evidence concerning what ECP data should be collected and best practice for commodity procurement and disbursement, financing for ECP, and ECP policy. As a result, there is little guidance for LMIC about how to prioritize the limited resources available for improving access to ECP. Little research learning has been documented and shared. This underlines the need to invest in strategic high quality research efforts to better understand what service delivery strategies work in specific contexts. There is also a need to identify lessons from successful (and unsuccessful) endeavours that can be applied by countries undertaking similar policy objectives as they relate to improving access to ECP.Despite the commercial sector providing a significant portion of SRH health services in LMIC This study may have been limited by an incomplete retrieval of research studies; however, efforts were made to search not only bibliographic databases but also meta-Indexes and the websites of international organizations. As a result more documents identified but despite meeting the appraisal criteria some of these may have been at a lower quality, as not all studies were published in peer reviewed journals. The application of a narrative synthesis to the results of the studies included in this review may have led to a loss of detail particularly of contextual factors that are important to the outcomes of the various interventions. However in this review textual descriptions of the studies provided a narrative that was maintained across all studies. The graphical elements included in the analysis were useful for identifying service delivery patterns and the tabulation of findings enabled structured comparisons across the interventions identified. A final limitation may have been our cut-off point of 10 years prior as more attention was paid to research on ECP introduction shortly after the dedicated product was made available, in the mid-late 1990s.ECP have been acknowledged as an essential commodity to prevent unwanted pregnancy and save women's lives; however women in LMIC face many barriers to accessing this contraceptive method. This review has identified a number of promising strategies to improving access including: advance provision of ECP; task shifting and sharing; intersectoral collaboration for sexual assault; m-health (the use of mobile devices such as mobile phones) for information provision and engagement of potential users; scale up through national family planning programs. However, the lack of high quality evidence resulting in few studies from which to glean comprehensive insights has led to the identification of a number of knowledge gaps. These gaps present a range of questions that should be the focus of research into how to best improve service delivery efforts for ECP. Checklist S1PRISMA checklist.(DOC)Click here for additional data file.


Initial diagnosis and staging of gynaecological malignancy is often the remit of the local general radiologist. The “incidentaloma” is not infrequently encountered on pelvic imaging undertaken for other indications. It can be daunting to those without a solid knowledge of the female pelvis.To recognise the spectrum of female pelvic malignancy and appreciate relevant incidental findings.To identify the pearls and pitfalls of diagnosis, understand important points in staging and restaging disease.To identify potential complications of both tumour and treatment and discuss imaging strategies in suspected local recurrence.We provide an overview of imaging modalities used, review pertinent anatomy and cover the spectrum of malignancy specific to the female pelvis, incorporating common and uncommon tumours. Emphasis is placed on imaging features that are important in treatment planning and evaluating prognosis.This exhibit will enhance the confidence of general radiologist in a district hospital setting when encountering potential female pelvic malignancy at initial diagnosis or when assessing for complications of tumour or treatment in the acute setting.


This paper discusses the contentious issue of reuse of stored biological samples and data obtained from research participants in past clinical research to answer future ethical and scientifically valid research questions. Many countries have regulations and guidelines that guide the use and exportation of stored biological samples and data. However, there are variations in regulations and guidelines governing the reuse of stored biological samples and data in Sub-Saharan Africa including Malawi.The current research ethics regulations and guidelines in Malawi do not allow indefinite storage and reuse of biological samples and data for future unspecified research. This comes even though the country has managed to answer pertinent research questions using stored biological samples and data. We acknowledge the limited technical expertise and equipment unavailable in Malawi that necessitates exportation of biological samples and data and the genuine concern raised by the regulatory authorities about the possible exploitation of biological samples and data by researchers. We also acknowledge that Malawi does not have bio-banks for storing biological samples and data for future research purposes. This creates room for possible exploitation of biological samples and data collected from research participants in primary research projects in Malawi. However, research ethics committees require completion and approval of material transfer agreements and data transfer agreements for biological samples and data collected for research purposes respectively and this requirement may partly address the concern raised by the regulatory authorities. Our concern though is that there is no such requirement for biological samples and data collected from patients for clinical or diagnostic purposes.In conclusion, we propose developing a medical data and material transfer agreement for biological samples and data collected from patients for clinical or diagnostic purposes in both public and private health facilities that may end up in research centers outside Malawi. We also propose revision of the current research ethics regulations and guidelines in Malawi in order to allow secondary use of biological samples and data collected from primary research projects as a way of maximizing the use of collected samples and data. Finally, we call for consultation of all stakeholders within the Malawi research community when regulatory authorities are developing policies that govern research in Malawi. Clinical research may sometimes involve exportation and importation of biological samples and data which serve as the back bone of viable scientific or biomedical research. As emerging innovations in the fields of genetics, genomics and biotechnology increase, the value of biological samples and data , 2 creatIn the United States of America (US), it is allowed to collect and store biological samples and data for future research. However, there are disagreements on the issue of informed consent. According to the US federal regulations “also known as the Common rule” or the Code of Federal Regulations (CFR), research on stored biological samples and data is explicitly exempt from review by institutional review boards (IRB) . This isn = 504) found that for biological samples and data derived from research, the majority of research participants would not require their consent for identifiable samples and data and even less than 12.1 % of the research participants would require consent for anonymized samples [It is important to note that these guidelines are not based on empirical research done on research participants but mostly on the interpretation held by the different bodies on the principle of respect for persons or autonomy and informed consent . A studyIntention for collecting the sample/data.Justification for requiring a biological sample/data.Duration for storage of the sample/data and its justification.The place where the sample/data will be kept.OwnershipControl of the sample/data.AccessMost countries in Sub-Saharan Africa require researchers from both academic and research institutions to complete material transfer agreement forms (MTAs) before shipping biological samples and data collected from research participants to academic or research institutions overseas, and mostly to developed countries. In the MTA forms, the researchers are required to justify importation and exportation of biological samples and data to the institutions in the developed countries where the samples and data are sent for further analyses and tests . Though However, there are variations in regulations governing use of biological samples and data in Sub-Saharan Africa. The National Health Act of 2003 of South Africa requires that research participants must provide informed consent before donating biological samples and data but the Act does not have guidelines on reuse of such samples and data in research . The Stan = 343) found that 95 % of the research participants would consent to reuse of samples and data without additional consent as long as the Institutional Review Board approved it [n = 600), 44.3 % of the participants felt consent forms should include a separate section for storage and future use of samples [n = 200), 77.5 % of the participants were comfortable with storage of samples while 12 % of the participants said they would require reasons for storage and would want to give separate consent for storage [The variations in national regulations and guidelines reflect the differing perspectives of research participants across several African countries. A study done in Uganda  as early as 1982 . The samn = 200), over a third (39.5 %) of participants indicated that “they would mind if researchers or research organizations generated profits from the research in which they were involved” [Malawi like other developing countries has limited capacity to conduct complex biomedical and genetic tests required to answer scientific and ethically valid questions. This has allowed researchers to obtain ethics approval from local ethics committees to export biological samples and data to countries where such biomedical and genetic tests are available. However, the regulatory authorities are concerned that these exported biological samples and data may be subject to abuse and exploitation by researchers. Indeed, international collaborative research has been subject to abuse and exploitation in the past and not only on issues of stored biological material . There hnvolved” . Of thisnvolved” .It should also be noted that while it is the duty of government and RECs to promote the interests of the research participants and prevent their exploitation, such efforts may amount to unnecessary paternalism if the affected research participants are not involved in such decisions . For exaJohn Rawls, one of the contemporary philosophers once stated that "justice as fairness serves as a basis of informed and willing political agreement between citizens viewed as free and equal persons “. Thus, wRestrictions on secondary use of biological samples and data imply that any tissue remaining at the completion of a particular study should either be kept in storage indefinitely or be disposed of. This amounts to wastage of valuable biological material that could be used to advance medical knowledge for better interventions and such a restriction is not cost effective. This restriction also subjects research participants to biological sample and data recollection in order to carry out secondary research. This exposes them to additional risk and contradicts the principle of non-maleficence.The restrictions set forth by Malawian regulations and guidelines also run the risk of selective justice which is another form of injustice. While being restrictive on biological samples and data derived from research, which is heavily controlled and closely monitored by research ethics committees, regulatory bodies are silent on samples and data derived from medical centers for clinical diagnosis that could end up in research centers. Therefore, we propose the introduction and utilization of a separate material transfer agreement which shall be called medical material transfer agreement (MMTA) for exportation of biological samples and data that are collected from patients in both private and public health facilities for clinical purposes.Both the National Health Sciences Research Committee and COMREC do require completion and approval of MTAs for biological samples and data collected in research settings. However, there is no data and material transfer agreement that is designed for biological samples and data collected in clinical settings that may later on be used for research purposes. This may create a gap for exploitation of biological samples and data collected for diagnostic purposes. Although comprehensive, the MTA in research settings does not address the issue of how samples and data will be handled after research activities are over. As such, there is still room for researchers to exploit biological samples and data collected for research purposes. Creating a bio-bank or bio-repository center in the country and requesting return of samples and data after a specified period may be a viable alternative to better regulate handling of human samples and data for medical research.However, we are of the opinion that broad consent for storage and future use of biological samples and data done at the time of sample and data collection may be the best model of consent to allow unspecified ethical research that will be reviewed and approved by an ethics committee . By defiThere are also other consent models which could be used. A multi-layered/tiered consent is a consent model in which research participants are given a set of options which allow them to select how they want to participate in the research. Multi-layered/tiered consent can used where researchers want to give options to research participants to choose whether they want their samples and data to be used in future studies or not . This emIn circumstances where the research ethics committee recommends re-consenting of research participants having obtained specific consent in primary research projects, researchers would then be obliged to do so but if it is not feasible to re-contact research participants for consent to use stored biological samples and data for other purposes, the research ethics committee may provide a waiver or may consent on behalf of the research participants. As Nienaber puts it, “research in vulnerable populations is not by definition exploitative and unethical” and “paternalistic attitudes are denigrating” . TherefoThe current view held by the National Health Sciences Research Committee and COMREC are restrictive and may prove to be detrimental to health research in Malawi. As such, there is need for review of the policy stand at the national level. Research participants must be allowed to give informed consent if they so wish or to decline use of their biological samples and data derived from them for any other purpose including in future research. As an important component of medical research, research participants’ autonomy should be respected by allowing them to decide what they feel is the best fate for their donated biological samples and data. This could either be biological sample/data reuse or destruction.Research ethics committees and regulatory bodies should continue doing vibrant reviews of medical research and put in place measures to avoid research participants’ exploitation and abuse. To better address regulatory bodies’ concern about exploitation of biological samples and data by researchers, further empirical social science research needs to be conducted locally to assess the views of research participants and the public on collection, storage and future reuse of biological samples and data and inform policy makers accordingly. There is also need to educate the public about the benefits of future use of biological samples and data.We also recommend that government and local research institutions should invest in developing infrastructure that will allow processing of biological samples and data locally. In the absence of local capacity, it is unfair to hinder exportation of biological samples and data for good biomedical research. This would allow better regulation of biological samples and data that are collected both for medical research and diagnostic purposes.There is also need to introduce a medical data and material transfer agreement document for biological samples and data derived in medical centers for clinical diagnostic purposes that could end up in research centers. The current policy is rigid and too strict on research derived samples and data but there is no strict control on biological samples and data derived from clinical investigations or procedures.The current framework is also silent on proof of destruction of biological samples and data when the research is over. Hence, we recommend the development of a local bio-bank in Malawi where biological samples and data should be returned after the agreed period of storage has passed. Since establishing a bio-bank is likely to take time, a remote site can keep the biological samples and data in storage while allowing Malawian researchers the right to access the biological samples and data.As genetic, genomic and biomedical research technologies become more advanced, biological samples and data collected for specific research objectives may be of great value to study other secondary outcomes. Where genetic and genomic studies are involved, we are aware that the National Health Sciences Research Committee is mandated to review them. However, in both clinical research and genetic/genomic studies, much emphasis should be placed on collection, storage and obtaining consent for future reuse of biological samples and data. This has the potential to greatly benefit the nation and the medical research community in Malawi. However, this can only occur if the guidelines governing such research are reasonable, fair and objective. It is therefore necessary to review existing guidelines and allow secondary use of stored biological samples and data. Asking research participants to donate a sample or data for each research question when new research questions could potentially be answered by already existing samples and data is unnecessary duplication and unfair. This underutilization of biological samples and data constitutes reckless wastage of valuable and scarce human biological samples and data. While we acknowledge the genuine ethical concern by the National Commission for Science and Technology that it is trying to avoid exploitation of biological samples and data collected in Malawi for research purposes, there is no empirical evidence that researchers can exploit samples and data they collect in primary research projects. In addition, the current regulatory framework is punitive to those who want to be efficient for other emerging research questions. Too much restriction may also undermine training of local researchers as most high technology research is currently conducted outside the country.


Beilstein Journal of Organic Chemistry on natural products in 2011 and 2013 [Artemisia annua [Streptomyces avermitilis at the famous Kitasato Institute and for the development of derivatives that are used as highly potent anthelmintics both for animal and human welfare [As a continuation of the first two Thematic Series in the  welfare . Current welfare ), analyt welfare , gene sy welfare  offer an welfare  continueBeilstein Journal of Organic Chemistry and also the whole team at the Beilstein-Institut for their professional work. I wish the readers of the present Thematic Series joyful reading and hopefully new inspiration for their own research.I thank all contributors that participated in this third Thematic Series on natural product chemistry in the Jeroen S. DickschatBonn, February 2016


Preventing Chronic Disease (PCD) has issued a special call for student papers for our Student Research Paper Contest. This year PCD received 67 submissions from students throughout the world. We are very excited to recognize Kathleen Li and colleagues as the winners of the 2014 contest for their paper entitled “Evaluation of the Placement of Mobile Fruit and Vegetable Vendors to Alleviate Food Deserts in New York City”  and with the multiple rounds of review of the top 15 papers  also contributed countless hours reviewing and commenting on these manuscripts. I especially want to recognize Dr Deesha Patel, our 2013 student winner, who served as a reviewer this year. Congratulations and thank you for making the student contest a success!The Student Research Paper Contest is a great opportunity to recognize the outstanding work being done by the next generation of public health researchers and their mentors. In addition to the 67 students who submitted manuscripts, hundreds of mentors and colleagues supported these young investigators, and we want to recognize them. Without their contributions


A lack of social support and recognition by the environment is one of the most consistent risk factors for posttraumatic stress disorder (PTSD), and PTSD patients will recover faster with proper social support. The oxytocin system has been proposed to underlie beneficial effects of social support as it is implicated in both social bonding behavior and reducing stress responsivity, notably amygdala reactivity : BONDS standing for “Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology” in acutely traumatized persons admitted to the emergency department  enhanced psychotherapy in PTSD patients.


At 30 minutes the jacket and weighted rucksack are removed and at 45 minutes the remaining t-shirt is also removed. Patients continue to exercise for a minimum of 60 minutes or up to 90 minutes duration to determine whether thermal equilibrium  can be achieved. Patients achieving thermal balance are considered to show normal thermoregulation (and pass HTT), those who do not or have another medical issue identified are considered to be heat intolerant (fail). Those who do not pass the assessment are reviewed at least once a minimum of 8 weeks later. Measurements of rectal temperature, skin temperature, heart rate and sweat rate made during the HHT are used to determine whether an individual's heat intolerance relates to an abnormal level of heat production  or impaired heat dissipation mechanisms.Exertional heat stroke and heat illness (HI) continue to pose a significant threat to military training and operations in both temperate and hot climates. In 2001, the Institute of Naval Medicine (INM) established a formal protocol for Heat Tolerance Testing (HTT) and in 2003 it became UK Armed Forces Policy that personnel who have been diagnosed as having suffered from an episode of heat stroke or HI with a significant biochemical disturbance or multiple episodes of HI are referred to the Heat Illness Clinic (HIC) at the INM. Following a full medical examination and assessment of maximal aerobic fitness (VOPatient outcomes of the HTT reported for those who attended in 2014 were reviewed.In 2014, 140 patients were assessed in the INM HIC, assessment outcomes are shown in Table Only a small number of the HI casualties referred to the HIC demonstrate abnormal thermoregulation. Although the HTT appears to discriminate between individuals with normal and abnormal thermoregulation further work is required to confirm the specificity and sensitivity of the HTT.


In 2014, the first national report providing surveillance data for antibiotic consumption in England was published by the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) [Rx-info and IMS Health are commercial organisations specialising in the provision of prescribing data for healthcare. Data from IMS Health was used to collate information on antibiotic use in secondary care for the ESPAUR report. The report showed considerable variability in the extent of antibiotic prescribing across different areas within England. While IMS Health and Rx-info each have formal internal quality assurance processes, there has been no external validation of the data when used for the purpose of comparison or benchmarking. The National Health Service (NHS) England will include validation of hospital prescribing data as part of the antimicrobial quality premium  in 2015/16.To develop a national protocol for validating antimicrobial consumption data in acute NHS hospitals in England.A validation protocol was designed and piloted in acute NHS hospitals. Each was sent the protocol along with a workbook to enable each hospital to submit antimicrobial consumption data from their own pharmacy system. These data were analysed alongside that from IMS Health and Rx-info. Participating hospitals were also sent a questionnaire to gather feedback on the pilot validation protocol to help inform the final national protocol.Forty-five (out of acute 156) NHS Trusts participated in the pilot. The pilot protocol and questionnaire feedback enabled the development of a national validation protocol which was published in March 2015.All acute NHS hospitals in England will be encouraged to use the national protocol to validate antimicrobial prescribing data to ensure correct and meaningful data for the purpose of benchmarking and antibiotic stewardship.None declared.


Pilot and feasibility studies underpin much of current health related research, including randomised controlled trials. The number of reports in which authors describe their studies as pilot or feasibility studies is increasing. In spite of recent attempts to define pilot and feasibility studies, the research community has differing views about these definitions.We will present a framework for defining pilot and feasibility studies conducted in advance of randomised controlled trials designed to assess the effect of an intervention. The framework was developed using: a Delphi consensus study (93 participants); an open meeting at the 2nd International Clinical Trials Methodology Conference in 2013 (15 participants); a review of definitions outside the health research context; an international expert consensus meeting (26 participants); and a review of published empirical studies described as pilot or feasibility (27 studies).The framework uses feasibility as an umbrella term with pilot studies as a subset of feasibility studies; it does not use mutually exclusive definitions of pilot and feasibility studies. The framework involves straightforward definitions and can be represented in a simple diagram. We will show how it is consistent with the common usage of these terms in the literature, and with the UK Medical Research Council framework for complex interventions. Additionally although the UK National Institute for Health Research does imply that feasibility and pilot studies are mutually exclusive, their definitions can be mapped onto the framework. This work is part of a larger programme of work on pilot and feasibility studies.


Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer’s diseases (AD) tissues including cerebral spinal fluid (CSF), showing that levels of Reelin fragments are altered in AD compared to control. Potential key proteases involved in Reelin proteolysis have recently been defined, identifying processes that could be altered in neurodegeneration. Introduction of full-length Reelin and its proteolytic fragments into several mouse models of neurodegeneration and neuropsychiatric disorders quickly promote learning and memory. These findings support a role for Reelin in learning and memory and suggest further understanding of these processes are important to harness the potential of this pathway in treating cognitive symptoms in neuropsychiatric and neurodegenerative diseases. Neurodegenerative diseases are characterized by the progressive loss of synapses and neurons, accounting for cognitive deterioration. One molecular pathway that is well characterized in playing a role in adult synaptic plasticity and learning and memory is the Reelin signaling pathway  receptor insertion, and can contribute to the induction and enhancement of long-term potentiation  and Apolipoprotein receptor 2  and repeats 6–7  peptide, and neurofibrillary tangles composed of modified versions of the tau protein  of Reelin and its fragments has demonstrated significant improvements in models of Reelin deficiency (Rogers et al., ALL wrote the review and generated the figures. EJW and GWR edited the content and structure of the review. Each author contributed ideas of topics for inclusion.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.


We study random strongly heterogeneous recurrent networks of firing rate neurons, introducing the notion of cohorts: groups of co-active neurons, who compete for firing with one another and whose presence depends sensitively on the structure of the input. The identities of neurons recruited to and dropped from an active cohort changes smoothly with varying input features. We search for network parameter regimes in which the activation of cohorts is robust yet easily switchable by the external input and which exhibit large repertoires of different cohorts. We apply these networks to model the emergence of orientation and direction selectivity in visual cortex. We feed these random networks with a set of harmonic inputs that vary across neurons only in their temporal phase, mimicking the feedforward drive due to a moving grating stimulus. The relationship between the phases that carries the information about the orientation of the stimulus determines which cohort of neurons is activated. As a result the individual neurons acquire non-monotonic orientation tuning curves which are characterized by high orientation and direction selectivity. This mechanism of emergence for direction selectivity differs from the classical motion detector scheme, which is based on the nonlinear summation of the time-shifted inputs. In our model these two mechanisms coexist in the same network, but can be distinguished by their different frequency and contrast dependences. In general, the mechanism we are studying here converts temporal phase sequence into population activity and could therefore be used to extract and represent also various other relevant stimulus features.


Respondents were randomly allocated to one of the following three question formats: The dichotomous choice referendum, the dissonance minimizing referendum and the two-sided payment ladder. The data can be used to investigate the influence of alternative statistical approaches on the willingness to pay measures and their comparison across question formats.The dataset includes responses from a contingent valuation study about the national climate change mitigation policies in Germany. The online survey was carried out in the spring of 2014. It assesses the willingness to pay for an increase of the national CO Specifications TableValue of the data•The data is designed for evaluating influences of different question formats on willingness to pay.•Additionally the data contains a rich set of attitudinal variables.•The data can be used to explore the influence of alternative statistical approaches on willingness to pay measures.•The data facilitates evaluation of different methods to compare willingness to pay across dichotomous and continuous question formats.12 reduction goal. The sample is representative for the German population between 18 and 69 by sex and age. The data is used to estimate willingness to pay across different question formats in "The Role of Question Format for the Support for National Climate Change Mitigation Policies in Germany and the Determinants of WTP" The data set contains 1512 records obtained from a nationwide web-based survey of WTP for new or intensified climate change mitigation policies that are needed to reach Germany׳s CO22 reduction target of 30% to 40% by 2020 compared to 1990. The target increase from 30% to 40% was selected for the contingent valuation (CV) scenario because it closely represents Germany׳s climate change mitigation strategy.The questionnaire is designed to evaluate willingness to pay (WTP) in Germany for an increase in the COThe three versions of the questionnaire differed only by question format. The question formats employed are the dichotomous choice (DC) referendum, the dissonance minimizing (DM) referendum and the two-way payment ladder (TWPL). The DM referendum provides further categories to the standard DC referendum, which allow the respondent to express favour for the referendum without having to agree to pay the posted price The questionnaire is structured as follows: After a few introductory questions an information screen informed briefly about possible climate change mitigation measures that are prominent in the public discussion about the climate policy mix in Germany. After the information screen, subjects were presented a short cheap talk script and afterwards the CV scenario with the varying question formats.


One key debate in memory research centers around the problem of representation. How is information represented in memory and how do the principles that govern memory representations change across the short and long term? One class of memory models  information from memory. Elhalal et al.  have intWe conclude by highlighting several venues for future research. Recent advances in neuroscience now enable powerful approaches that combine behavioral indices along with complementary neuroscience methods that can utilize univariate and multivariate analyses of neuroimaging data on healthy individuals, as well as transcranial magnetic stimulation and lesion studies to test and infer similarities and dissociations across the hypothesized states of memory. The literature would benefit from computational memory models that can account for the recent neural findings . A more in-depth investigation of the neural correlates of the FoA is also warranted. Recent neuroimaging work has implicated the posterior parietal cortex and the lateral inferior temporal cortex (Öztekin et al., 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 vestibular system is crucial for postural control; however there are considerable differences in the task dependence and frequency response of vestibular reflexes in appendicular and axial muscles. For example, vestibular reflexes are only evoked in appendicular muscles when vestibular information is relevant to postural control, while in neck muscles they are maintained regardless of the requirement to maintain head on trunk balance. Recent investigations have also shown that the bandwidth of vestibular input on neck muscles is much broader than appendicular muscles (up to a factor of 3). This result challenges the notion that vestibular reflexes only contribute to postural control across the behavioral and physiological frequency range of the vestibular organ . In this review, we explore and integrate these task-, muscle- and frequency-related differences in the vestibular system’s contribution to posture, and propose that the human nervous system has adapted vestibular signals to match the mechanical properties of the system that each group of muscles controls. The vestibular system senses linear and angular head motion in space. This sensory information is used by the central nervous system to elicit reflexes and control appendicular, axial and extraocular muscles that are crucial for posture and gaze. Vestibular reflexes vary across and within muscle groups and are modulated by spatial and temporal factors related to a muscle’s contribution to the system dynamics, the different neural pathways innervating each muscle, and the congruency of sensory signals and motor commands for a given task. Recent findings from our lab indicate that these modulating mechanisms may be related to the frequency content of the vestibular signals impinging on the different muscles. Like many electromechanical systems, the vestibular system’s input-output response varies with stimulus frequency, and like many biological systems, the bandwidth of this frequency response has evolved to match the mechanical system being controlled. This review examines the frequency response of the vestibular system’s reflexive control of posture. More specifically, it focuses on the differences in the frequency response and task dependence of vestibular reflexes controlling appendicular and spinal muscles in order to better understand the neurophysiological principles governing how humans achieve stable upright posture of the head and body. We argue that the frequency response of vestibular reflexes is governed by the mechanical systems under their control, with the neck system exhibiting a broader bandwidth than the appendicular muscles. The higher frequency response in neck muscles can be modulated but not inhibited, and in contrast to the lower frequency response observed in the appendicular muscles, its contribution to muscle activity does not dependent on a neck muscle’s contribution to postural control. Based on this evidence, we propose the higher frequency response of the vestibulocollic reflexes (VCR) is functionally similar to the vestibulo-ocular response for the coordination of eye-head movements as well as head postural control during gaze shifts.The frequency response of the vestibular system is governed by the electromechanical properties of the sensory organs and the various neural structures and pathways that then carry these sensory signals to motor neurons  exhibit head rotational velocity profiles containing frequency information approaching 20 Hz  of turtle otoliths during inertial stimuli reaches 500 Hz and resembles that of a linear second order system with a natural frequency at ~400 Hz . This processing depends on the afferent’s intrinsic membrane electrophysiology and can differ within and across nuclei  response latencies  on the vestibular—and more generally the sensorimotor—control of standing has yet to be established. For instance, increased muscle stiffness, as experienced by Parkinson patients, could be simulated in healthy controls in order to understand its effects on sensorimotor processing during standing balance. Robotic balance simulators  short-duration biphasic waveform  response dynamics in the sternocleidomastoid muscle are insensitive to changes in vision, external support, stance width and posture  also varied little between isometric tasks involving different neck muscle activation patterns with equivalent activation levels. For example, similar VCR responses were observed in the sternocleidomastoid muscle during isometric contractions in flexion and yaw, as well as in the splenius capitis muscle during isometric contractions in extension and yaw. This low sensitivity to the combination of muscles being activated highlights the flexibility in neck muscle control, where the activation of a group of muscles does not have strong reciprocal (inhibitory or excitatory) connections to other muscles  is related to the bandwidth of the mechanical system under control, which for the head-neck system during voluntary movements and imposed force perturbations is up to 5 times wider compared to the whole body during standing balance . Although modulation of higher frequencies (up to 70 Hz) in neck muscles was observed in some conditions , this part of the neck vestibular reflexes frequency response were maintained even in conditions where the muscle did not directly contribute to postural control. The absence of a reduced high-frequency VCR response with the head fixed parallels the response of the electrically evoked VOR, which occurs regardless of the functional or postural state of the head and body (Aw et al., Furthermore, the VOR is subject to suppression during gaze shifts and gaze pursuit, where an intact VOR would be counterproductive to the intended change in gaze or ongoing tracking (see review, Cullen and Roy, The data reviewed here have important implications for understanding the role of the vestibular system in controlling posture and gaze. Indeed, studying separately individual effectors controlled by the vestibular system would lead to diverging conclusions regarding its role in a specific task. A similar statement could be made for the examined bandwidth of the vestibular reflexes. We instead propose an integrative approach that simultaneously examines the complete frequency response of vestibular reflexes in appendicular, spinal and extraocular muscles. Using combinations of robotic systems and electrical vestibular stimulation, it may be possible to evaluate the relative dependence or independence of vestibular input on axial and appendicular systems. The evaluation of vestibular input expressed in multiple motor systems will provide a more comprehensive understanding of how the vestibular system contributes to the complex behavioral tasks of daily living.G.P. Siegmund owns shares in a consulting company, and both he and the company may derive benefit from being associated with this work. All other 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.


Dear Sir,The revolutionary forces at play in medical education are full steam ahead. From PBL, TBL and the flipped classroom, which has barely had time to cement itself we might add, we are now faced with the prospect of massive open online courses (MOOCs) and synchronous massive online courses (SMOCs).MOOCs or massive open online courses are still fairly premature in the field of medicine with limited courses currently available. Examples in present use include Introductory Human Physiology by Coursera and Fundamentals of Clinical Trials courtesy of edX. From a learning perspective we can only hypothesize the potential benefits of such a movement. For instance, students may gain an enhanced understanding of pathology not common to their resident country or gain further understanding of hard to grasp concepts by clinicians renowned in their field of expertise.Whilst medical schools are not currently offering academic credits for MOOC courses, the American Council on Education has certified four Coursera courses  so that However, just like the flipped classroom, the dust has been barely left to settle following the arrival of MOOCs as a result of the recently announced SMOCs which may hold greater promise . GoslingWhatever the future holds for medical education, it is sure to continue to amaze many an instructor and we for one feel it should be embraced wholeheartedly.


Plain English summaries (PESs) are a valuable tool for making research findings available and accessible to patients and the public. They provide brief descriptions of research written in non-specialist language. The National Institute for Health Research Journals Library (NIHRJL) currently requires authors to provide a 250 word PES. This is published online as part of the final, open-access report. Practice varies among other funders and journals, some of whom employ independent external writers (IEWs) for this purpose.To compare ease of reading and understanding of PESs written by clinical trial teams and an IEW.Forty reports undergoing the editorial process for the NIHRJL will be included in the study. The PES for each report will be revised by authors in line with detailed guidance and edited by an IEW.Ease of reading will be measured using the Flesch Reading Ease score. Scores range from 0-100; higher scores indicate text that is easier to read. Ease of understanding will be assessed by asking public reviewers to read a selection of PESs and rate them from 1 (did not understand) to 4 . Statistical comparison of group scores will be reported.High quality PESs are a priority for dissemination of clinical trial results to patients and the public but it is currently unclear who is best placed to produce them. Results of this study will inform future practice for the NIHRJL and will be relevant to all agencies communicating trial findings to patients and the public.


Given a perfect superposition of  Generation of non-classical states of light compatible with atomic quantum memory has been an outstanding challenge driven by various applications in quantum information processing On the other hand, several specific quantum algorithms have been discovered , we denote by We want to end with a summary and a discussion of a number of open questions related to the proposed algorithm and its possible applications to problems beyond the quantum memory. The underlying idea of the proposed algorithm is very general and consists of employing Hamming distance to transform the superposition state into a specific quantum state. The crucial advantage is that any required quantum state can now be exactly created using these simple operations. Novel type of applications can be formed in quantum storage protocols based on photon echo techniques. Also, because the dynamical model used here can be equally realized in multi-qubit models, an exponential propagation of quantum excitation along a large number of qubits is in principle possible.


Diabetes mellitus is increasing, so it is relevant to plan services to prevent vision loss from diabetic retinopathy. There are 3 target groups to consider:the communitypeople known to have diabetes mellitus (DM)people with sight-threatening diabetic retinopathy (STDR)In order to provide the relevant services that each group needs, it is useful to undertake a situational analysis to set priorities and develop an action plan.We must work out how many people need the two key services required to address DR: case detection  and treatment of sight threatening retinopathy .Case detection. How many people with diabetes will need an annual eye examination?Treatment. How many people with sight threatening diabetic retinopathy will need treatment?In order to answer question 1, we need to estimate:The size of the population (over 20 years old) in the country or district proportion of the population (over 20 years old) with diabetes mellitus (available at www.diabetesatlas.org)The number of people with diabetes who will need an annual eye examination.Then it is straightforward to calculate the total In order to answer question 2, we need to estimate:The number of people over 20 years old with diabetes (the answer to question 1)proportion of people with diabetes who have sight-threatening DR (STDR). A reasonable estimate in low-income countries is 10% of all people with diabetesThe Summarise your answers to questions 1 and 2 in Knowing what the need for services is, estimate what is being done at present and summarise this in The following activities all help to ensure that everyone with diabetes and STDR are able to access screening and treatment services. They are ordered, starting with activities conducted by the eye health team and then radiating out into the general hospital and eventually into the community.Which of the following are currently being done, at local and national level?Diagnosing and treating patients with STDR attending an eye clinic (with/without outreach clinics)Examining all patients with diabetes for STDR at hospital diabetes clinics (with/without outreach clinics)Creating a register of all known people with diabetes mellitus and calling people for an annual eye examinationIdentifying people with undiagnosed diabetes and STDR in the communityEducating health professionals about diabetes and STDREducating the communityWho are the health professionals able to offer screening services?Who are the health professionals able to offer treatment for STDR?What equipment is available for diagnosis?What equipment is available for treatment?What management protocols are available?Is there a database of patient records?What is the financial support?What is the leadership for the service?What statistics and information are collected and monitored What patient information materials are available?Who are the stakeholders? Having completed this situational analysis, you can decide what are the next priorities and what are the important actions that need to be taken to improve the DR service.