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Setting: Research capacity is weakest in low and middle-income countries (LMICs) where operational research is highly relevant and needed. Structured Operational Research and Training Initiative (SORT IT) courses have been developed to train participants to conduct and publish operational research and influence policy and practice. Twenty courses were completed in Asia, Africa, Europe and the South Pacific between 2009 and 2014. Objectives: In the 20 completed SORT IT courses, to assess where the research was conducted, who was trained, who became facilitators in subsequent courses and course outcomes. Design: A cohort study of completed SORT IT courses Results: There were 236 participants (41% female) including 64 nationalities who conducted research in 59 countries, mostly from Asia and Africa (mean course duration = 9.7 months). Most participants (68%) were from government health programs and non-governmental agencies. A total of 213(90%) participants completed all milestones successfully with 41(19%) becoming subsequent course facilitators, 88% of whom were from LMICs. Of 228 manuscripts submitted to scientific journals, 197(86%) were either published or in press; in 86%, the principal investigator (first author) was a LMIC national. Papers were published in 23 scientific journals (impact factor 0.5–4.4) and covered 21 disease categories (median publication time = 5.7 months). Published papers (186) had 94,794 cumulative article views/downloads. Article views/downloads for immediate open access articles were double those from closed access journals. Conclusion: The SORT IT model has been effective in training personnel to produce relevant operational research in LMICs. It merits continued commitment and support for further scale-up and development. [ABSTRACT FROM AUTHOR]

Introduction: Translational research is central to international health policy, research and funding initiatives. Despite increasing use of the term, the translation of basic science discoveries into clinical practice is not straightforward. This systematic search and narrative synthesis aimed to examine factors enabling or hindering translational research from the perspective of basic and clinician scientists, a key stakeholder group in translational research, and to draw policy-relevant implications for organisations seeking to optimise translational research opportunities. Methods and Results: We searched SCOPUS and Web of Science from inception until April 2015 for papers reporting scientists’ views of the factors they perceive as enabling or hindering the conduct of translational research. We screened 8,295 papers from electronic database searches and 20 papers from hand searches and citation tracking, identifying 26 studies of qualitative, quantitative or mixed method designs. We used a narrative synthesis approach and identified the following themes: 1) differing concepts of translational research 2) research processes as a barrier to translational research; 3) perceived cultural divide between research and clinical care; 4) interdisciplinary collaboration as enabling translation research, but dependent on the quality of prior and current social relationships; 5) translational research as entrepreneurial science. Across all five themes, factors enabling or hindering translational research were largely shaped by wider social, organisational, and structural factors. Conclusion: To optimise translational research, policy could consider refining translational research models to better reflect scientists’ experiences, fostering greater collaboration and buy in from all types of scientists. Organisations could foster cultural change, ensuring that organisational practices and systems keep pace with the change in knowledge production brought about by the translational research agenda. [ABSTRACT FROM AUTHOR]

Background: Distant metastasis or local recurrence after primary tumour resection remain a major clinical problem. The anaesthetic technique used during oncologic surgery is suggested to influence the metastatic process. While awaiting the results of ongoing randomised controlled trials (RCTs), we have analyzed the evidence regarding the influence of anaesthetic drugs on experimental tumour metastasis in animal studies. Methods: PubMed and Embase were searched until April 21st, 2015. Studies were included in the systematic review when they 1) assessed the effect of an anaesthetic drug used in clinical practice on the number or incidence of metastasis in animal models with experimental cancer, 2) included an appropriate control group, and 3) presented unique data. Results: 20 studies met the inclusion criteria (published between 1958–2010). Data on number of metastases could be retrieved from 17 studies. These studies described 41 independent comparisons, 33 of which could be included in the meta-analysis (MA). The incidence of metastases was studied in 3 unique papers. From these 3 papers, data on 7 independent comparisons could be extracted and included in the MA. Locally administered local anaesthetics appear to decrease the number of metastases (SMD -6.15 [-8.42; -3.88]), whereas general anaesthetics (RD: 0.136 [0.045, 0.226]), and more specifically volatile anaesthetics (SMD 0.54 [0.24; 0.84]), appear to increase the number and risk of metastases in animal models for cancer. Conclusions: Anaesthetics influence the number and incidence of metastases in experimental cancer models. Although more high quality experimental research is necessary, based on the currently available evidence from animal studies, there is no indication to suggest that locally administered local anaesthetics are harmful during surgery in cancer patients. Volatile anaesthetics, however, might increase metastasis in animal models and clinical trials investigating this possibly harmful effect should receive priority. The results of our systematic review in animal studies are broadly consistent with clinical reports that anaesthetic technique does seem to affect the tumour metastasis process. [ABSTRACT FROM AUTHOR]

In biomedicine, scientific literature is a valuable source for knowledge discovery. Mining knowledge from textual data has become an ever important task as the volume of scientific literature is growing unprecedentedly. In this paper, we propose a framework for examining a certain disease based on existing information provided by scientific literature. Disease-related entities that include diseases, drugs, and genes are systematically extracted and analyzed using a three-level network-based approach. A paper-entity network and an entity co-occurrence network (macro-level) are explored and used to construct six entity specific networks (meso-level). Important diseases, drugs, and genes as well as salient entity relations (micro-level) are identified from these networks. Results obtained from the literature-based literature mining can serve to assist clinical applications. [ABSTRACT FROM AUTHOR]

The body of science evaluating the potential impacts of unconventional natural gas development (UNGD) has grown significantly in recent years, although many data gaps remain. Still, a broad empirical understanding of the impacts is beginning to emerge amidst a swell of research. The present categorical assessment provides an overview of the peer-reviewed scientific literature from 2009–2015 as it relates to the potential impacts of UNGD on public health, water quality, and air quality. We have categorized all available original research during this time period in an attempt to understand the weight and direction of the scientific literature. Our results indicate that at least 685 papers have been published in peer-reviewed scientific journals that are relevant to assessing the impacts of UNGD. 84% of public health studies contain findings that indicate public health hazards, elevated risks, or adverse health outcomes; 69% of water quality studies contain findings that indicate potential, positive association, or actual incidence of water contamination; and 87% of air quality studies contain findings that indicate elevated air pollutant emissions and/or atmospheric concentrations. This paper demonstrates that the weight of the findings in the scientific literature indicates hazards and elevated risks to human health as well as possible adverse health outcomes associated with UNGD. There are limitations to this type of assessment and it is only intended to provide a snapshot of the scientific knowledge based on the available literature. However, this work can be used to identify themes that lie in or across studies, to prioritize future research, and to provide an empirical foundation for policy decisions. [ABSTRACT FROM AUTHOR]

Background: Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. Methods: Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. Results: A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4–90.1%) and 62.5% (95% CI 24.5–91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. Conclusions: Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens. [ABSTRACT FROM AUTHOR]

Racial segregation, and in particular school segregation, likely plays an important role in affecting health outcomes. To examine this connection, this paper explores the relationship between the end of court-ordered school desegregation and preterm births among Blacks using birth certificate information between 1992 and 2002 (n = 183,178). The end of court-ordered oversight has important implications for the level of racial segregation in schools: If residential segregation remains high, neighborhood-based student assignment plans would naturally increase school segregation. A rise in school segregation may lead to worse educational, labor, and health outcomes among Blacks. Using multiple difference-in-differences framework that exploits variation in exposure to schools that declared unitary status, it finds that school districts’ release from court oversight is associated with a 0.8 percentage point increase in preterm births among Black mothers. This paper contributes to literature that finds that the end of court-ordered school desegregation in the 1990s have negative implications for Blacks. More research should be conducted to understand the causal relationship between school segregation and infant health. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, the focus of mental health care has shifted from institutionalisation to community-based programs and short hospital stays. This change means that there is an increased role for caregivers, mostly family members, in managing persons with mental illness. Although there is evidence to support the benefits of deinstitutionalisation of mental health care, there are also indications of substantial burden experienced by caregivers; the evidence of which is limited in sub-Saharan Africa. However, knowledge of the nature and extent of this burden can inform the planning of mental health services that will not only benefit patients, but also caregivers and households. Objective: To systematically review the available evidence on the economic burden of severe mental illness on primary family caregivers in sub-Saharan Africa. Methods: A comprehensive search was conducted in Pubmed, CINAHL, Econlit and Web of Science with no date limitations up to September 2016 using keywords such as "burden", "cost of illness" and "economic burden" to identify relevant published literature. Articles were appraised using a standardised data extraction tool covering themes such as physical, psychological and socioeconomic burden. Results: Seven papers were included in the review. Caregivers were mostly family members with a mean age of 46.34, female and unemployed. Five out of seven studies (71%) estimated the full economic burden of severe mental illness on caregivers. The remainder of studies just described the caregiver burden. All seven papers reported moderate to severe caregiver burden characterised by financial constraint, productivity loss and lost employment. The caregiver’s level of income and employment status, severity of patient's condition and duration of mental illness were reported to negatively affect the economic burden experienced by caregivers. Conclusion: There is paucity of studies reporting the burden of severe mental illness on caregivers in sub-Saharan Africa. Further research is needed to present the nature and extent of this burden to inform service planning and policymaking. [ABSTRACT FROM AUTHOR]

The ensemble method random forests has become a popular classification tool in bioinformatics and related fields. The out-of-bag error is an error estimation technique often used to evaluate the accuracy of a random forest and to select appropriate values for tuning parameters, such as the number of candidate predictors that are randomly drawn for a split, referred to as mtry. However, for binary classification problems with metric predictors it has been shown that the out-of-bag error can overestimate the true prediction error depending on the choices of random forests parameters. Based on simulated and real data this paper aims to identify settings for which this overestimation is likely. It is, moreover, questionable whether the out-of-bag error can be used in classification tasks for selecting tuning parameters like mtry, because the overestimation is seen to depend on the parameter mtry. The simulation-based and real-data based studies with metric predictor variables performed in this paper show that the overestimation is largest in balanced settings and in settings with few observations, a large number of predictor variables, small correlations between predictors and weak effects. There was hardly any impact of the overestimation on tuning parameter selection. However, although the prediction performance of random forests was not substantially affected when using the out-of-bag error for tuning parameter selection in the present studies, one cannot be sure that this applies to all future data. For settings with metric predictor variables it is therefore strongly recommended to use stratified subsampling with sampling fractions that are proportional to the class sizes for both tuning parameter selection and error estimation in random forests. This yielded less biased estimates of the true prediction error. In unbalanced settings, in which there is a strong interest in predicting observations from the smaller classes well, sampling the same number of observations from each class is a promising alternative. [ABSTRACT FROM AUTHOR]

To become integrated into an ant society, myrmecophilous parasites must overcome both the defenses and the communication system of their hosts. Some aleocharine staphylinid beetles employ chemical and tactile strategies to invade colonies, where they later consume ant brood and participate in parasitic trophallaxis with host ants. By producing compounds that both appease their hosts and stimulate adoption, the beetles are able to live in and deposit their own eggs in the well defended ant nest. In the current paper, previous findings on the myrmecophilous behavior and morphological features of the staphylinid beetle Lomechusoides (formerly Lomechusa) strumosus are reviewed and re-evaluated. Hitherto unpublished results concerning the beetles’ ability to participate in the social food flow of their host ants are reported. Furthermore, we present an analysis and documentation of the behavioral interactions between beetles and host ants during the adoption process, and we report new histological and scanning electron microscopic analyses of the exocrine glands and morphological adaptations that underlie the myrmecophilous behavior of L. strumosus. The main features of L. strumosus are compared with those of the staphilinid myrmecophile Lomechusa (formerly Atemeles) pubicollis. The paper concludes with a description of the life trajectory of L. strumosus and presents a brief history and discussion of the hypotheses concerning the evolution of myrmecophily in L. strumosus and other highly adapted myrmecophilous parasites. [ABSTRACT FROM AUTHOR]

Introduction: Homebirths are common in low and middle income countries and are associated with poor child survival. We assessed the feasibility of using smartphones by village health workers for pregnancy registration and the effectiveness of health text messages (SMS) sent to pregnant women through village health workers in reducing homebirths in rural Uganda. Methods: A non-randomised intervention study was undertaken in 26 villages. In the intervention arm, village health workers registered pregnant women (n = 262) in 13 villages using a smartphone app (doForm) and paper forms and gestation age-timed SMS were sent through village health workers to the pregnant women. In 13 control villages, (n = 263) pregnant women were registered on paper forms only and no SMS was sent. The main outcome was place of birth measured through a self-report. Logistic regression with generalised estimating equations was used to explore the effect of the intervention. Results: Comparing 795 corresponding data fields on phone and paper revealed that numeric variable fields were 86%-95% similar while text fields were 38%-48% similar. Of the 525 pregnant women followed, 83 (15.8%) delivered at home. In the adjusted analysis, the intervention was associated with lower odds of homebirths [AOR = 0.38, 95%CI (0.15–0.97)]. Muslim religion [AOR = 4.0, 95%CI (1.72–9.34)], primary or no maternal education [AOR = 2.51, 95%CI (1.00–6.35)] and health facility distance ≥ 2 km [AOR = 2.26, 95%CI (0.95–5.40)] were independently associated with homebirths. Conclusion: Village health workers can register pregnant women at home using phones and relay gestation age specific SMS to them to effectively reduce homebirths. [ABSTRACT FROM AUTHOR]

Context: In response to political and social factors over the last sixty years mental health systems internationally have endeavoured to transfer the delivery of care from hospitals into community settings. As a result, there has been increased emphasis on the need for better quality care planning and care coordination between hospital services, community services and patients and their informal carers. The aim of this systematic review of international research is to explore which interventions have proved more or less effective in promoting personalized, recovery oriented care planning and coordination for community mental health service users. Methods: A systematic meta-narrative review of research from 1990 to the present was undertaken. From an initial return of 3940 papers a total of 50 research articles fulfilled the inclusion criteria, including research from the UK, Australia and the USA. Findings: Three research traditions are identified consisting of (a) research that evaluates the effects of government policies on the organization, management and delivery of services; (b) evaluations of attempts to improve organizational and service delivery efficiency; (c) service-users and carers experiences of community mental health care coordination and planning and their involvement in research. The review found no seminal papers in terms of high citation rates, or papers that were consistently cited over time. The traditions of research in this topic area have formed reactively in response to frequent and often unpredictable policy changes, rather than proactively as a result of intrinsic academic or intellectual activity. This may explain the absence of seminal literature within the subject field. As a result, the research tradition within this specific area of mental health service delivery has a relatively short history, with no one dominant researcher or researchers, tradition or seminal studies amongst or across the three traditions identified. Conclusions: The research findings reviewed suggests a gap has existed internationally over several decades between policy aspirations and service level interventions aimed at improving personalised care planning and coordination and the realities of everyday practices and experiences of service users and carers. Substantial barriers to involvement are created through poor information exchange and insufficient opportunities for care negotiation. [ABSTRACT FROM AUTHOR]

Background: Clubfeet are commonly treated using the Ponseti method. This method involves weekly manipulation and casting which gradually corrects the position of the foot. However, the reasons for following a weekly interval are not clear. Question / Purpose: The aim is to investigate the influence of the cast change interval on treatment outcomes in the Ponseti method. Methods: We performed a systematic review of comparative studies in which the cast change interval was varied. Scientific databases were searched for relevant publications, screened for eligibility and assessed for a risk of bias. A 'best evidence' synthesis tool was used to synthesize the results of the included studies and draw conclusions from relevant clinical outcomes. Results: Nine papers matched the inclusion criteria, which provided data of 587 subjects who had a total of 870 clubfeet. There is strong evidence for a positive relation between cast change interval and treatment duration. However, there is no evidence for any relation between the cast change interval and the required number of casts, tenotomy rate, required surgery or failure rate. Conclusions: Accelerated versions are as effective and safe as the traditional Ponseti method. However, more research is needed to assess the long-term results and to identify an optimal cast change interval. [ABSTRACT FROM AUTHOR]

Background: Due to the disease’s progressive nature, advance care planning (ACP) is recommended for people with early stage dementia. General practitioners (GPs) should initiate ACP because of their longstanding relationships with their patients and their early involvement with the disease, however ACP is seldom applied. Aim: To determine the barriers and facilitators faced by GPs related to ACP with people with dementia. Data sources: We systematically searched the relevant databases for papers published between January 1995 and December 2016, using the terms: primary healthcare, GP, dementia, and ACP. We conducted a systematic integrative review following Whittemore and Knafl’s method. Papers containing empirical data about GP barriers and/or facilitators regarding ACP for people with dementia were included. We evaluated quality using the Mixed-Method-Appraisal-Tool and analyzed data using qualitative content analysis. Results: Ten qualitative, five quantitative, and one mixed-method paper revealed four themes: timely initiation of ACP, stakeholder engagement, important aspects of ACP the conversation, and prerequisites for ACP. Important barriers were: uncertainty about the timing of ACP, how to plan for an uncertain future, lack of knowledge about dementia, difficulties assessing people with dementia’s decisional capacities, and changing preferences. Facilitators for ACP were: an early start when cognitive decline is still mild, inclusion of all stakeholders, and discussing social and medical issues aimed at maintaining normal life. Conclusion: Discussing future care is difficult due to uncertainties about the future and the decisional capacities of people with dementia. Based on the facilitators, we recommend that GPs use a timely and goal-oriented approach and involve all stakeholders. ACP discussions should focus on the ability of people with dementia to maintain normal daily function as well as on their quality of life, instead of end-of-life-discussions only. GPs need training to acquire knowledge and skills to timely initiate collaborative ACP discussions. [ABSTRACT FROM AUTHOR]

Background: Risk perception has been found to be a crucial factor explaining inconsistent or non-use of HIV prevention interventions. Considerations of risk need to expand beyond risk of infection to also include the personal, social, emotional, and economic risks associated with prevention intervention use. Objectives: This systematic review of qualitative peer-reviewed literature from sub-Saharan Africa examines perceptions of risk associated with HIV infection and HIV prevention intervention use. Data sources: We searched Medline, Embase, PsychInfo, Africa Wide Info, CINAHL, and Global Health for publications and screened them for relevance. Study eligibility criteria: Peer-reviewed qualitative studies published since 2003 were eligible for inclusion if they examined risk perception or uncertainty in the context of a medically regulated intervention. Only studies focusing on adults were included. Study appraisal and synthesis methods: Included publications were quality assessed using the Hawker method and coded thematically. Results: 10318 unique papers were identified, of which 29 are included. Among the themes identified, a particularly salient one was the potential of HIV prevention interventions to threaten the stability of a relationship and impact on how and when people may—or may not—choose to use prevention interventions. Limitations: This literature review excludes grey-literature, which may have distinct valuable insights. We also excluded quantitative studies that may have challenged or triangulated our findings. Conclusions and implications: When considering the risk of HIV acquisition, it is insufficient to examine biological risk in isolation from the personal, relational and economic costs associated with intervention use. This loss of emotional, physical, or material support may be perceived as more consequential than the prevention of a potential infection. [ABSTRACT FROM AUTHOR]

China’s fast economic growth contributes to the rapid development of its urbanization process, and also renders a series of industrial accidents, which often cause loss of life, damage to property and environment, thus requiring the associated risk analysis and safety control measures to be implemented in advance. However, incompleteness of historical failure data before the occurrence of accidents makes it difficult to use traditional risk analysis approaches such as probabilistic risk analysis in many cases. This paper aims to develop a new methodology capable of assessing regional industrial safety (RIS) in an uncertain environment. A hierarchical structure for modelling the risks influencing RIS is first constructed. The hybrid of evidential reasoning (ER) and Analytical Hierarchy Process (AHP) is then used to assess the risks in a complementary way, in which AHP is hired to evaluate the weight of each risk factor and ER is employed to synthesise the safety evaluations of the investigated region(s) against the risk factors from the bottom to the top level in the hierarchy. The successful application of the hybrid approach in a real case analysis of RIS in several major districts of Beijing (capital of China) demonstrates its feasibility as well as provides risk analysts and safety engineers with useful insights on effective solutions to comprehensive risk assessment of RIS in metropolitan cities. The contribution of this paper is made by the findings on the comparison of risk levels of RIS at different regions against various risk factors so that best practices from the good performer(s) can be used to improve the safety of the others. [ABSTRACT FROM AUTHOR]

Recommender systems are vulnerable to shilling attacks. Forged user-generated content data, such as user ratings and reviews, are used by attackers to manipulate recommendation rankings. Shilling attack detection in recommender systems is of great significance to maintain the fairness and sustainability of recommender systems. The current studies have problems in terms of the poor universality of algorithms, difficulty in selection of user profile attributes, and lack of an optimization mechanism. In this paper, a shilling behaviour detection structure based on abnormal group user findings and rating time series analysis is proposed. This paper adds to the current understanding in the field by studying the credibility evaluation model in-depth based on the rating prediction model to derive proximity-based predictions. A method for detecting suspicious ratings based on suspicious time windows and target item analysis is proposed. Suspicious rating time segments are determined by constructing a time series, and data streams of the rating items are examined and suspicious rating segments are checked. To analyse features of shilling attacks by a group user’s credibility, an abnormal group user discovery method based on time series and time window is proposed. Standard testing datasets are used to verify the effect of the proposed method. [ABSTRACT FROM AUTHOR]

Miniaturization of computer hardware and the demand for network capable devices has resulted in the emergence of a new class of technology called wearable computing. Wearable devices have many purposes like lifestyle support, health monitoring, fitness monitoring, entertainment, industrial uses, and gaming. Wearable devices are hurriedly being marketed in an attempt to capture an emerging market. Owing to this, some devices do not adequately address the need for security. To enable virtualization and connectivity wearable devices sense and transmit data, therefore it is essential that the device, its data and the user are protected. In this paper the use of novel Integrated Circuit Metric (ICMetric) technology for the provision of security in wearable devices has been suggested. ICMetric technology uses the features of a device to generate an identification which is then used for the provision of cryptographic services. This paper explores how a device ICMetric can be generated by using the accelerometer and gyroscope sensor. Since wearable devices often operate in a group setting the work also focuses on generating a group identification which is then used to deliver services like authentication, confidentiality, secure admission and symmetric key generation. Experiment and simulation results prove that the scheme offers high levels of security without compromising on resource demands. [ABSTRACT FROM AUTHOR]

Competitive pressure to maximize the current bibliometric measures of productivity is jeopardizing the integrity of the scientific literature. Efforts are underway to address the ‘reproducibility crisis’ by encouraging the use of more rigorous, confirmatory methods. However, as long as productivity continues to be defined by the number of discoveries scientists publish, the impact factor of the journals they publish in and the number of times their papers are cited, they will be reluctant to accept high quality methods and consistently conduct and publish confirmatory/replication studies. This exploratory study examined a sample of rigorous Phase II-IV clinical trials, including unpublished studies, to determine if more appropriate metrics and incentives can be developed. The results suggest that rigorous procedures will help reduce false positives, but to the extent that higher quality methods are accepted as the standard of practice, the current bibliometric incentives will discourage innovative studies and encourage scientists to shift their research to less informative studies of subjects that are already being more actively investigated. However, the results also suggest that it is possible to develop a more appropriate system of rewards. In contrast to the current bibliometric incentives, evaluations of the quality of the methods and reproducibility of the results, innovation and diversity of thought, and amount of information produced may serve as measures and incentives that maintain the integrity of the scientific literature and maximize scientific progress. [ABSTRACT FROM AUTHOR]

This paper addresses patient-reported outcomes (PROs) and telemonitoring in congestive heart failure (CHF), both increasingly important topics. The interest in CHF trials is shifting from hard end-points such as hospitalization and mortality, to softer end-points such health-related quality of life. However, the relation of these softer end-points to objective parameters is not well studied. Telemonitoring is suitable for collecting both patient-reported outcomes and objective parameters. Most telemonitoring studies, however, do not take full advantage of the available sensor technology and intelligent data analysis. The Chiron clinical observational study was performed among 24 CHF patients (17 men and 7 women, age 62.9 ± 9.4 years, 15 NYHA class II and 9 class III, 10 of ishaemic, aetiology, 6 dilated, 2 valvular, and 6 of multiple aetiologies or cardiomyopathy) in Italy and UK. A large number of physiological and ambient parameters were collected by wearable and other devices, together with PROs describing how well the patients felt, over 1,086 days of observation. The resulting data were mined for relations between the objective parameters and the PROs. The objective parameters (humidity, ambient temperature, blood pressure, SpO2, and sweeting intensity) could predict the PROs with accuracies up to 86% and AUC up to 0.83, making this the first report providing evidence for ambient and physiological parameters to be objectively related to PROs in CHF patients. We also analyzed the relations in the predictive models, gaining some insights into what affects the feeling of health, which was also generally not attempted in previous investigations. The paper strongly points to the possibility of using PROs as primary end-points in future trials. [ABSTRACT FROM AUTHOR]

In his 2016 paper, Myhrvold criticized ours from 2014 on maximum growth rates (Gmax, maximum gain in body mass observed within a time unit throughout an individual’s ontogeny) and thermoregulation strategies (ectothermy, endothermy) of 17 dinosaurs. In our paper, we showed that Gmax values of similar-sized extant ectothermic and endothermic vertebrates overlap. This strongly questions a correct assignment of a thermoregulation strategy to a dinosaur only based on its Gmax and (adult) body mass (M). Contrary, Gmax separated similar-sized extant reptiles and birds (Sauropsida) and Gmax values of our studied dinosaurs were similar to those seen in extant similar-sized (if necessary scaled-up) fast growing ectothermic reptiles. Myhrvold examined two hypotheses (H1 and H2) regarding our study. However, we did neither infer dinosaurian thermoregulation strategies from group-wide averages (H1) nor were our results based on that Gmax and metabolic rate (MR) are related (H2). In order to assess whether single dinosaurian Gmax values fit to those of extant endotherms (birds) or of ectotherms (reptiles), we already used a method suggested by Myhrvold to avoid H1, and we only discussed pros and cons of a relation between Gmax and MR and did not apply it (H2). We appreciate Myhrvold’s efforts in eliminating the correlation between Gmax and M in order to statistically improve vertebrate scaling regressions on maximum gain in body mass. However, we show here that his mass-specific maximum growth rate (kC) replacing Gmax (= MkC) does not model the expected higher mass gain in larger than in smaller species for any set of species. We also comment on, why we considered extant reptiles and birds as reference models for extinct dinosaurs and why we used phylogenetically-informed regression analysis throughout our study. Finally, we question several arguments given in Myhrvold in order to support his results. [ABSTRACT FROM AUTHOR]

Griebeler and Werner offer a formal comment on Myhrvold, 2016 defending the conclusions of Werner and Griebeler, 2014. Although the comment criticizes several aspects of methodology in Myhrvold, 2016, all three papers concur on a key conclusion: the metabolism of extant endotherms and ectotherms cannot be reliably classified using growth-rate allometry, because the growth rates of extant endotherms and ectotherms overlap. A key point of disagreement is that the 2014 paper concluded that despite this general case, one can nevertheless classify dinosaurs as ectotherms from their growth rate allometry. The 2014 conclusion is based on two factors: the assertion (made without any supporting arguments) that the comparison with dinosaurs must be restricted only to extant sauropsids, ignoring other vertebrate groups, and that extant sauropsid endotherm and ectotherm growth rates in a data set studied in the 2014 work do not overlap. The Griebeler and Werner formal comment presents their first arguments in support of the restriction proposition. In this response I show that this restriction is unsupported by established principles of phylogenetic comparison. In addition, I show that the data set studied in their 2014 work does show overlap, and that this is visible in one of its figures. I explain how either point effectively invalidates the conclusion of their 2014 paper. I also address the other methodological criticisms of Myhrvold 2016, and find them unsupported. [ABSTRACT FROM AUTHOR]

In this paper, we will investigate the effect of diffusion, which is ubiquitous in nature, on the immune system using a reaction-diffusion model in order to understand the dynamical behavior of complex patterns and control the dynamics of different patterns. Through control theory and linear stability analysis of local equilibrium, we obtain the optimal condition under which the system loses stability and a Turing pattern occurs. By combining mathematical analysis and numerical simulation, we show the possible patterns and how these patterns evolve. In addition, we establish a bridge between the complex patterns and the biological mechanism using the results from a previous study in Nature Cell Biology. The results in this paper can help us better understand the biological significance of the immune system. [ABSTRACT FROM AUTHOR]

This paper extends the observations presented in the previously published work on the afterhyperpolarization (AHP) duration changes in motoneurones (MNs) on the paretic (more affected) side of 11 post-stroke patients by the same analysis on the non-paretic (less-affected) side. The estimated AHP duration for patients’ MNs supplying more-affected muscles was significantly longer than control values and the elongation decreased with patient age and disorder duration. For MNs supplying less-affected muscles, dependency of AHP duration on age was closer to the control data, but the scatter was substantially bigger. However, the AHP duration estimate of less-affected MNs tended to be longer than that of controls in the short time elapsed since the stroke, and shorter than controls in the long time. Our results thus suggest that the spinal MNs on both sides respond to the cerebral stroke rapidly with prolongation of AHP duration, which tends to normalize with time, in line with functional recovery. This suggestion is in concert with the published research on post-stroke changes in brain hemispheres. To our knowledge, these dependencies have never been investigated before. Since the number of our data was limited, the observed trends should be verified in a larger sample of patients and such a verification could take into account the suggestions for data analysis that we provide in this paper. Our data are in line with the earlier published research on MN firing characteristics post-stroke and support the conclusion that the MUs of the muscles at the non-paretic side are also affected and cannot be considered a suitable control for the MUs on the paretic side. [ABSTRACT FROM AUTHOR]

We aimed to assess which factors correlate with collaborative behavior and whether such behavior associates with scientific impact (citations and becoming a principal investigator). We used the R index which is defined for each author as log(Np)/log(I1), where I1 is the number of co-authors who appear in at least I1 papers written by that author and Np are his/her total papers. Higher R means lower collaborative behavior, i.e. not working much with others, or not collaborating repeatedly with the same co-authors. Across 249,054 researchers who had published ≥30 papers in 2000–2015 but had not published anything before 2000, R varied across scientific fields. Lower values of R (more collaboration) were seen in physics, medicine, infectious disease and brain sciences and higher values of R were seen for social science, computer science and engineering. Among the 9,314 most productive researchers already reaching Np ≥ 30 and I1 ≥ 4 by the end of 2006, R mostly remained stable for most fields from 2006 to 2015 with small increases seen in physics, chemistry, and medicine. Both US-based authorship and male gender were associated with higher values of R (lower collaboration), although the effect was small. Lower values of R (more collaboration) were associated with higher citation impact (h-index), and the effect was stronger in certain fields (physics, medicine, engineering, health sciences) than in others (brain sciences, computer science, infectious disease, chemistry). Finally, for a subset of 400 U.S. researchers in medicine, infectious disease and brain sciences, higher R (lower collaboration) was associated with a higher chance of being a principal investigator by 2016. Our analysis maps the patterns and evolution of collaborative behavior across scientific disciplines. [ABSTRACT FROM AUTHOR]

Introduction: Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries. Methods: A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). Results: Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231–3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395–4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs. Conclusion: ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations. [ABSTRACT FROM AUTHOR]

A ‘meta-analysis’ was performed to determine effects of post-hatch food and water deprivation (PHFWD) on chicken development, performance and welfare (including health). Two types of meta-analysis were performed on peer-reviewed scientific publications: a quantitative ‘meta-analysis’ (MA) and a qualitative analysis (QA). Previously reported effects of PHFWD were quantified in the MA, for variables related to performance, mortality and relative yolk sac weight. The QA counted the number of studies reporting (non-)significant effects when five or more records were available in the data set (i.e. relative heart, liver and pancreas weight; plasma T3, T4 and glucose concentrations; relative duodenum, jejunum and ileum weight; duodenum, jejunum and ileum length; and villus height and crypt depth in duodenum, jejunum and ileum). MA results indicated that 24 hours of PHFWD (i.e. ≥12–36 hours) or more resulted in significantly lower body weights compared to early-fed chickens up to six weeks of age. Body weights and food intake were more reduced as durations of PHFWD (24, 48, 72, ≥84 hours) increased. Feed conversion rate increased in chickens up to 21 and 42 days of age after ≥84 hours PHFWD in comparison with chickens fed earlier. Total mortality at day 42 was higher in chickens after 48 hours PHFWD compared to early fed chickens or chickens after 24 hours PHFWD. First week mortality was higher in chickens after ≥84 hours PHFWD than in early fed chickens. The MA for relative yolk sac weight was inconclusive for PHFWD. The QA for plasma T3, T4 and glucose concentrations indicated mainly short-term decreases in T3 and glucose in PHFWD chickens compared to early fed chickens, and no effects of PHFWD on T4 concentrations. Relative weights of liver, pancreas and heart were lower after PHFWD, but only in the first week of life. A retarded development of gut segments (duodenum, jejunum and ileum) was found in the first week of life, measured as shorter, lower relative weight, and lower villus height and crypt depth. It is concluded that 48 hours (≥36–60 hours) PHFWD leads to lower body weights and higher total mortality in chickens up to six weeks of age, the latter suggesting compromised chicken welfare, but effects of PHFWD on organ development and physiological status appear to be mainly short-term. [ABSTRACT FROM AUTHOR]

Background: Posterior tibial tendon dysfunction (PTTD) and adult acquired flatfoot deformity (AAFD) are used interchangeably, although both suggest quite different pathological processes. Objective: To investigate key differences in selection criteria used for inclusion into research studies. Methods: An electronic database search was performed from inception to June 2016. All primary research articles with clear inclusion/diagnostic criteria for PTTD or AAFD were included in the review. All criteria were extracted and synthesised into one aggregate list. Frequencies of recurring criteria were calculated and reported for each stage of the conditions. Results: Of the potentially eligible papers, 148 (65%) did not specify inclusion/selection criteria for PTTD or AAFD and were excluded. Eligibility criteria were reported 82 times in the 80 included papers, with 69 descriptions for PTTD and 13 for AAFD. After synthesis of criteria from all papers, there were 18 key signs and symptoms. Signs and symptoms were considered to be those relating to tendon pathology and those relating to structural deformity. The total number of individual inclusion/diagnostic criteria ranged from 2 to 9. The majority of articles required signs of both tendon dysfunction and structural deformity (84% for AAFD and 81% for PTTD). Across both groups, the most frequently reported criteria were abduction of the forefoot (11.5% of total criteria used), the presence of a flexible deformity (10.2%) and difficulty performing a single leg heel raise (10.0%). This was largely the case for the PTTD articles, whereas the AAFD articles were more focused on postural issues such as forefoot abduction, medial arch collapse, and hindfoot valgus (each 16.7%). Conclusion: As well as synthesising the available literature and providing reporting recommendations, this review has identified that many papers investigating PTTD/AAFD do not state condition-specific selection criteria and that this limits their clinical applicability. Key signs and symptoms of PTTD and AAFD appear similar, except in early PTTD where no structural deformity is present. We recommend that PTTD is the preferred terminology for the condition associated with signs of local tendon dysfunction with pain and/or swelling along the tendon and difficulty with inversion and/or single leg heel raise characterising stage I and difficulty with single leg heel raise and a flexible flatfoot deformity characterizing stage II PTTD. While AAFD may be useful as an umbrella term for acquired flatfoot deformities, the specific associated aetiology should be reported in studies to aid consolidation and implementation of research into practice. Trial registration: Prospero ID: [ABSTRACT FROM AUTHOR]

Publication metadata help deliver rich analyses of scholarly communication. However, research concepts and ideas are more effectively expressed through unstructured fields such as full texts. Thus, the goals of this paper are to employ a full-text enabled method to extract terms relevant to disciplinary vocabularies, and through them, to understand the relationships between disciplines. This paper uses an efficient, domain-independent term extraction method to extract disciplinary vocabularies from a large multidisciplinary corpus of PLoS ONE publications. It finds a power-law pattern in the frequency distributions of terms present in each discipline, indicating a semantic richness potentially sufficient for further study and advanced analysis. The salient relationships amongst these vocabularies become apparent in application of a principal component analysis. For example, Mathematics and Computer and Information Sciences were found to have similar vocabulary use patterns along with Engineering and Physics; while Chemistry and the Social Sciences were found to exhibit contrasting vocabulary use patterns along with the Earth Sciences and Chemistry. These results have implications to studies of scholarly communication as scholars attempt to identify the epistemological cultures of disciplines, and as a full text-based methodology could lead to machine learning applications in the automated classification of scholarly work according to disciplinary vocabularies. [ABSTRACT FROM AUTHOR]

Budding yeast, which undergoes polarized growth during budding and mating, has been a useful model system to study cell polarization. Bud sites are selected differently in haploid and diploid yeast cells: haploid cells bud in an axial manner, while diploid cells bud in a bipolar manner. While previous studies have been focused on the molecular details of the bud site selection and polarity establishment, not much is known about how different budding patterns give rise to different functions at the population level. In this paper, we develop a two-dimensional agent-based model to study budding yeast colonies with cell-type specific biological processes, such as budding, mating, mating type switch, consumption of nutrients, and cell death. The model demonstrates that the axial budding pattern enhances mating probability at an early stage and the bipolar budding pattern improves colony development under nutrient limitation. Our results suggest that the frequency of mating type switch might control the trade-off between diploidization and inbreeding. The effect of cellular aging is also studied through our model. Based on the simulations, colonies initiated by an aged haploid cell show declined mating probability at an early stage and recover as the rejuvenated offsprings become the majority. Colonies initiated with aged diploid cells do not show disadvantage in colony expansion possibly due to the fact that young cells contribute the most to colony expansion. [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s disease neuroimaging initiative (ADNI) is a landmark imaging and omics study in AD. ADNI research literature has increased substantially over the past decade, which poses challenges for effectively communicating information about the results and impact of ADNI-related studies. In this work, we employed advanced information visualization techniques to perform a comprehensive and systematic mapping of the ADNI scientific growth and impact over a period of 12 years. Methods: Citation information of ADNI-related publications from 01/01/2003 to 05/12/2015 were downloaded from the Scopus database. Five fields, including authors, years, affiliations, sources (journals), and keywords, were extracted and preprocessed. Statistical analyses were performed on basic publication data as well as journal and citations information. Science mapping workflows were conducted using the Science of Science (Sci2) Tool to generate geospatial, topical, and collaboration visualizations at the micro (individual) to macro (global) levels such as geospatial layouts of institutional collaboration networks, keyword co-occurrence networks, and author collaboration networks evolving over time. Results: During the studied period, 996 ADNI manuscripts were published across 233 journals and conference proceedings. The number of publications grew linearly from 2008 to 2015, so did the number of involved institutions. ADNI publications received much more citations than typical papers from the same set of journals. Collaborations were visualized at multiple levels, including authors, institutions, and research areas. The evolution of key ADNI research topics was also plotted over the studied period. Conclusions: Both statistical and visualization results demonstrate the increasing attention of ADNI research, strong citation impact of ADNI publications, the expanding collaboration networks among researchers, institutions and ADNI core areas, and the dynamic evolution of ADNI research topics. The visualizations presented here can help improve daily decision making based on a deep understanding of existing patterns and trends using proven and replicable data analysis and visualization methods. They have great potential to provide new insights and actionable knowledge for helping translational research in AD. [ABSTRACT FROM AUTHOR]

For the past 50 years, acknowledgments have been studied as important paratextual traces of research practices, collaboration, and infrastructure in science. Since 2008, funding acknowledgments have been indexed by Web of Science, supporting large-scale analyses of research funding. Applying advanced linguistic methods as well as Correspondence Analysis to more than one million acknowledgments from research articles and reviews published in 2015, this paper aims to go beyond funding disclosure and study the main types of contributions found in acknowledgments on a large scale and through disciplinary comparisons. Our analysis shows that technical support is more frequently acknowledged by scholars in Chemistry, Physics and Engineering. Earth and Space, Professional Fields, and Social Sciences are more likely to acknowledge contributions from colleagues, editors, and reviewers, while Biology acknowledgments put more emphasis on logistics and fieldwork-related tasks. Conflicts of interest disclosures (or lack of thereof) are more frequently found in acknowledgments from Clinical Medicine, Health and, to a lesser extent, Psychology. These results demonstrate that acknowledgment practices truly do vary across disciplines and that this can lead to important further research beyond the sole interest in funding. [ABSTRACT FROM AUTHOR]

Background: In Australia, pre-exposure prophylaxis (PrEP) is targeted to individuals at high risk for HIV infection. We describe the HIV risk profile and characteristics of PRELUDE participants, and evaluate the population validity of the sample in representing high-risk gay and bisexual men (GBM) eligible for PrEP. Methods: PRELUDE is an on-going, open-label, single-arm observational study. Participants were identified in clinics and screened for eligibility using a paper-based risk assessment tool which followed the New South Wales (NSW) PrEP guidelines. Selection was validated using an independent online behavioural survey, completed by study participants upon enrolment. Demographic information was analysed using descriptive statistics, and kappa tests were used to determine agreement between reporting of high-risk practices in the risk assessment and behavioural survey. Results: During 2014–15, 471 individuals were targeted for enrolment; 341 were assessed for PrEP eligibility and 313 were enrolled. Of these, 303 (97%) identified as GBM. Overall, 85% of GBM met at least one high-risk criterion; 68% reported receptive intercourse with an HIV-positive or unknown status casual male partner, and 37% reported methamphetamine use in the three months preceding enrolment. The remaining 15% were enrolled based on medium-risk behaviours, or at the clinicians’ discretion. We found an 82% total agreement between self-reported high-risk behaviour and clinicians’ categorisation of GBM as being at high risk for HIV based on PrEP eligibility criteria. Conclusions: Behavioural eligibility criteria used by clinicians successfully identified individuals at high risk for HIV infection. This targeted approach ensures that the greatest public health and HIV prevention benefits can be derived in a setting without universal access to PrEP. [ABSTRACT FROM AUTHOR]

Background: Non-surgical interventions for adolescents with idiopathic scoliosis remain highly controversial. Despite the publication of numerous reviews no explicit methodological evaluation of papers labeled as, or having a layout of, a systematic review, addressing this subject matter, is available. Objectives: Analysis and comparison of the content, methodology, and evidence-base from systematic reviews regarding non-surgical interventions for adolescents with idiopathic scoliosis. Design: Systematic overview of systematic reviews. Methods: Articles meeting the minimal criteria for a systematic review, regarding any non-surgical intervention for adolescent idiopathic scoliosis, with any outcomes measured, were included. Multiple general and systematic review specific databases, guideline registries, reference lists and websites of institutions were searched. The AMSTAR tool was used to critically appraise the methodology, and the Oxford Centre for Evidence Based Medicine and the Joanna Briggs Institute’s hierarchies were applied to analyze the levels of evidence from included reviews. Results: From 469 citations, twenty one papers were included for analysis. Five reviews assessed the effectiveness of scoliosis-specific exercise treatments, four assessed manual therapies, five evaluated bracing, four assessed different combinations of interventions, and one evaluated usual physical activity. Two reviews addressed the adverse effects of bracing. Two papers were high quality Cochrane reviews, Three were of moderate, and the remaining sixteen were of low or very low methodological quality. The level of evidence of these reviews ranged from 1 or 1+ to 4, and in some reviews, due to their low methodological quality and/or poor reporting, this could not be established. Conclusions: Higher quality reviews indicate that generally there is insufficient evidence to make a judgment on whether non-surgical interventions in adolescent idiopathic scoliosis are effective. Papers labeled as systematic reviews need to be considered in terms of their methodological rigor; otherwise they may be mistakenly regarded as high quality sources of evidence. Protocol registry number: CRD42013003538, PROSPERO [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment, colloquially termed “chemobrain”, occurs in 10–40% of all cancer patients, and is an emerging target of cancer survivorship research. Aim: This study reviews published qualitative studies to explore cognitive impairments or chemobrain among breast cancer survivors, with particular attention given to the impact on quality of life. Method: Using keywords, we searched ten electronic databases (CINAHL, EMBASE, Proquest, OVID SP, MEDLINE, Oxford Journal, Science Direct, PubMED). Findings: Of 457 papers, seven relevant papers were included. Data was extracted and concepts were analysed using a meta ethnography approach. Four second order intepretations were identified, on the basis of which, four third order intrepretations were constructed. Linked together in a line of argument, was a consistent account on their struggles to self-manage the chemobrain impairments that impact their daily lives. Five concepts emerged from the analysis of the primary findings: i) real experiences of cognitive changes, ii) calls for help, iii) impact of cognitive impairments, iv) coping and v) survivorship and meaning. Further synthesis resulted in four new order intepretations: i) The chemobrain struggle, ii) The substantial impact of chemobrain on life domains, iii) The struggle to readjust and to self manage, and iv) ‘thankful yet fearful’ representation. Discussion: Awareness of cognitive changes were context-dependent on healthcare settings and cultural contexts as strong determinants. Subjects verified the existence of chemobrain but healthcare providers mis-recognised, under-recognised, and sometimes negated it perhaps due to its unknown aetiology. Asian breast cancer survivors appear less vocal than their western counterparts. Conclusion: The current literature on the lived experiences of how women experienced chemobrain provides a consistent report that chemobrain is real, persistent and with detrimental impacts on quality of life - manifested as a constant struggles. A greater awareness of the effects of chemobrain with improved functional assessment and interventions is warranted. [ABSTRACT FROM AUTHOR]

Longitudinal designs provide a strong inferential basis for uncovering reciprocal effects or causality between variables. For this analytic purpose, a cross-lagged panel model (CLPM) has been widely used in medical research, but the use of the CLPM has recently been criticized in methodological literature because parameter estimates in the CLPM conflate between-person and within-person processes. The aim of this study is to present some alternative models of the CLPM that can be used to examine reciprocal effects, and to illustrate potential consequences of ignoring the issue. A literature search, case studies, and simulation studies are used for this purpose. We examined more than 300 medical papers published since 2009 that applied cross-lagged longitudinal models, finding that in all studies only a single model (typically the CLPM) was performed and potential alternative models were not considered to test reciprocal effects. In 49% of the studies, only two time points were used, which makes it impossible to test alternative models. Case studies and simulation studies showed that the CLPM and alternative models often produce different (or even inconsistent) parameter estimates for reciprocal effects, suggesting that research that relies only on the CLPM may draw erroneous conclusions about the presence, predominance, and sign of reciprocal effects. Simulation studies also showed that alternative models are sometimes susceptible to improper solutions, even when reseachers do not misspecify the model. [ABSTRACT FROM AUTHOR]

Methods have been developed for Mendelian randomization that can obtain consistent causal estimates under weaker assumptions than the standard instrumental variable assumptions. The median-based estimator and MR-Egger are examples of such methods. However, these methods can be sensitive to genetic variants with heterogeneous causal estimates. Such heterogeneity may arise from over-dispersion in the causal estimates, or specific variants with outlying causal estimates. In this paper, we develop three extensions to robust methods for Mendelian randomization with summarized data: 1) robust regression (MM-estimation); 2) penalized weights; and 3) Lasso penalization. Methods using these approaches are considered in two applied examples: one where there is evidence of over-dispersion in the causal estimates (the causal effect of body mass index on schizophrenia risk), and the other containing outliers (the causal effect of low-density lipoprotein cholesterol on Alzheimer’s disease risk). Through an extensive simulation study, we demonstrate that robust regression applied to the inverse-variance weighted method with penalized weights is a worthwhile additional sensitivity analysis for Mendelian randomization to provide robustness to variants with outlying causal estimates. The results from the applied examples and simulation study highlight the importance of using methods that make different assumptions to assess the robustness of findings from Mendelian randomization investigations with multiple genetic variants. [ABSTRACT FROM AUTHOR]

Personal motivation is a key factor in the service of foster care, impending both on the welfare of the child and on the satisfaction of the carer. This paper explores the benefits, challenges and dilemmas involved in the job of professional (i.e. state-supported) foster carer in Romania–a country where the issue of child protection has drawn a great deal of international attention over the last thirty years. The principal hypothesis concerns whether the benefits, challenges and dilemmas identified by foster carers are influenced by the factors that led to their taking up this kind of work. Quantitative research was conducted using a questionnaire as the main tool. The paper takes a descriptive, cross-sectional and multifactorial approach. Sampling was carried out by self-selecting method, and the study involved 51 participants. The research project identified a statistically significant variation in the challenges and dilemmas reported by foster carers. Thus, the results of the study show that the majority of the carers indicate a primarily intrinsic motivation for their work. By way of conclusion, it is argued that social workers, operating in collaboration with multidisciplinary teams, can offer carers support in managing more difficult periods in the child–carer relationship, thus enhancing the sustainability of the foster care service. [ABSTRACT FROM AUTHOR]

Background: Resource allocation decisions for disease categories can be informed by proper estimates of the magnitude and distribution of total spending. In the backdrop of a high burden of Non-Communicable Diseases and Injuries (NCDI) in India, and a paucity of estimates on government spending on NCDI, this paper attempts to analyse public sector expenditure on NCDI spending in India. Methods: Various recent budget documents of the Centre and States/Union Territories have been used to extract expenditure on NCDI. The aggregates thus arrived at have been analysed to estimate aggregate and state level per capita spending. State level spending have been compared against disease burden using DALYs. Patterns of spending on NCDI across states were also analysed together with state level poverty to observe possible patterns. Findings: The total spending on NCDI by the government is low at less than 0.5% of GDP. NCDI spending is little more than one-fourth of total health spending of the country and most spending takes place at the state level (80%). The Ministry of Health and Family Welfare’s share in Central spending on NCDI is around 65%, and currently it spends 20% of its total health spending on NCDI. The gap between spending and DALYs is the most for the economically vulnerable states. Also, the states with high poverty levels also have low per capita expenditure on NCDI Interpretation: India does not depend on donor funding for health. It will have to step up domestic funding to address the increasing disease burden of NCDIs and to reduce the high out-of-pocket expenditure on NCDI. Policies on NCDI need to focus on UHC, service integration and personnel gaps. [ABSTRACT FROM AUTHOR]

Objective: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA. Methods: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy). Results: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events. Conclusion: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents. [ABSTRACT FROM AUTHOR]

This paper examines whether tobacco expenditure leads to the crowding out or crowding in of different expenditure items in South Africa. We apply genetic matching to expenditure quartiles of the 2010/2011 South African Income and Expenditure Survey. Genetic matching is a more appealing approach for dealing with the endogeneity of tobacco expenditure that often plagues studies using systems of demand equations. Further, genetic matching provides transparent measures of covariate balance giving the analyst objective means of assessing match success. We find that the poorest tobacco consuming households in South Africa consistently allocate smaller budget shares towards food items than non-smoking households. Specifically, we find that dairy, fruits, nuts and oils are displaced in favour of tobacco expenditure in the two poorest quartiles. Unsurprisingly, food items are never displaced for households in the top two quartiles, given these households’ greater access to resources. Like other studies in the literature, we find that tobacco expenditure consistently crowds-in alcohol across all quartiles confirming the strong complementarities between the two. [ABSTRACT FROM AUTHOR]

Background: HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy. Methods: A quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results: Nineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68–2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62–3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25–6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81–16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88–10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38–6.04) without obvious heterogeneity. Conclusions: HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries. [ABSTRACT FROM AUTHOR]

Background: Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods: The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results: In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions: The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: The application of health economic evaluation (HEE) evidence can play an important role in strategic planning and policy making. This study aimed to assess the scope and quality of existing research, with the goal of elucidating implications for improving the use of HEE evidence in Vietnam. Methods: A comprehensive search strategy was developed to search medical online databases (Medline, Google Scholar, and Vietnam Medical Databases) to select all types of HEE studies except cost-only analyses. Two researchers assessed the quality of selected studies using the Quality of Health Economic Studies (QHES) instrument. Results: We selected 26 studies, including 6 published in Vietnam. The majority of these studies focused on infectious diseases (14 studies), with HIV being the most common topic (5 studies). Most papers were cost-effectiveness studies that measured health outcomes using DALY units. Using QHES, we found that the overall quality of HEE studies published internationally was much higher (mean score 88.7+13.3) than that of those published in Vietnam (mean score 67.3+22.9). Lack of costing perspectives, reliable data sources and sensitivity analysis were the main shortcomings of the reviewed studies. Conclusion: This review indicates that HEE studies published in Vietnam are limited in scope and number, as well as by several important technical errors or omissions. It is necessary to formalize the process of health economic research in Vietnam and to institutionalize the links between researchers and policy-makers. Additionally, the quality of HEE should be enhanced through education about research techniques, and the implementation of standard HEE guidelines. [ABSTRACT FROM AUTHOR]

Background: Mobile health (mHealth) has undergone exponential growth in recent years. Patients and healthcare professionals are increasingly using health-related applications, at the same time as concerns about ethical issues, bias, conflicts of interest and privacy are emerging. The general aim of this paper is to provide an overview of the current state of development of mHealth. Methods and Findings: To exemplify the issues, we made a systematic review of the pain-related apps available in scientific databases (Medline, Web of Science, Gale, Psycinfo, etc.) and the main application shops (App Store, Blackberry App World, Google Play, Nokia Store and Windows Phone Store). Only applications (designed for both patients and clinicians) focused on pain education, assessment and treatment were included. Of the 47 papers published on 34 apps in scientific databases, none were available in the app shops. A total of 283 pain-related apps were found in the five shops searched, but no articles have been published on these apps. The main limitation of this review is that we did not look at all stores in all countries. Conclusions: There is a huge gap between the scientific and commercial faces of mHealth. Specific efforts are needed to facilitate knowledge translation and regulate commercial health-related apps. [ABSTRACT FROM AUTHOR]

Background: In August 2011, the German Protection against Infection Act was amended, mandating the reporting of healthcare associated infection (HAI) outbreak notifications by all healthcare workers in Germany via local public health authorities and federal states to the Robert Koch Institute (RKI). Objective: To describe the reported HAI-outbreaks and the surveillance system’s structure and capabilities. Methods: Information on each outbreak was collected using standard paper forms and notified to RKI. Notifications were screened daily and regularly analysed. Results: Between November 2011 and November 2012, 1,326 paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month. The main causative agent was norovirus (n = 414/578; 72%). Among the 108 outbreaks caused by bacteria, the most frequent pathogens were Clostridium difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug-resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks. Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to bacteria were mostly reported from intensive care units (ICUs) (45%), followed by internal medicine wards (16%). Conclusion: The mandatory HAI-outbreak surveillance system describes common outbreaks. Pathogens with a particular high potential to cause large or severe outbreaks may be identified, enabling us to further focus research and preventive measures. Increasing the sensitivity and reliability of the data collection further will facilitate identification of outbreaks able to increase in size and severity, and guide specific control measures to interrupt their propagation. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) analysis has quantified the functioning of the autonomic regulation of the heart and heart's ability to respond. However, majority of studies on HRV report several differences between patients with congestive heart failure (CHF) and healthy subjects, such as time-domain, frequency domain and nonlinear HRV measures. In the paper, we mainly presented a new approach to detect congestive heart failure (CHF) based on combination support vector machine (SVM) and three nonstandard heart rate variability (HRV) measures (e.g. SUM_TD, SUM_FD and SUM_IE). The CHF classification model was presented by using SVM classifier with the combination SUM_TD and SUM_FD. In the analysis performed, we found that the CHF classification algorithm could obtain the best performance with the CHF classification accuracy, sensitivity and specificity of 100%, 100%, 100%, respectively. [ABSTRACT FROM AUTHOR]

Background: Disorganised attachment patterns in infants have been linked to later psychopathology. Services have variable practices for identifying and providing interventions for families of children with disorganised attachment patterns, which is the attachment pattern leading to most future psychopathology. Several recent government reports have highlighted the need for better parenting interventions in at risk groups. Objectives: The objective of this review and meta-analysis was to evaluate the clinical effectiveness of available parenting interventions for families of children at high risk of developing, or already showing, a disorganised pattern of attachment. Methods: Population: Studies were included if they involved parents or caregivers of young children with a mean age under 13 years who had a disorganised classification of attachment or were identified as at high risk of developing such problems. Included interventions were aimed at parents or caregivers (e.g. foster carers) seeking to improve attachment. Comparators included an alternative intervention, an attention control, treatment as usual or no intervention. The primary outcome was a disorganised pattern in childhood measured using a validated attachment instrument. Studies that did not use a true Randomised Controlled Trial (RCT) design were excluded from the review. Both published and unpublished papers were included, there were no restrictions on years since publication and foreign language papers were included where translation services could be accessed within necessary timescales. Results: A comprehensive search of relevant databases yielded 15,298 papers. This paper reports a systematic review as part of an NIHR HTA study identifying studies pre-2012, updated to include all papers to October 2016. Two independent reviewers undertook two stage screening and data extraction of the included studies at all stages. A Cochrane quality assessment was carried out to assess the risk of bias. In total, fourteen studies were included in the review. In a meta-analysis of these fourteen studies the interventions saw less disorganised attachment at outcome compared to the control (OR = 0.50, (0.32, 0.77), p = 0.008). The majority of the interventions targeted maternal sensitivity. We carried out exploratory analyses to examine factors that may influence treatment outcome but these should be treated with caution given that we were limited by small numbers of studies. Conclusions: Parenting interventions that target parental sensitivity show promise in reducing disorganised attachment. This is limited by few high quality studies and the fact that most studies are with mothers. More high quality randomised controlled trials are required to elucidate this further. [ABSTRACT FROM AUTHOR]

This paper examined, with a behavioral paradigm, to what extent people choose to view stimuli that portray death, violence or harm. Based on briefly presented visual cues, participants made choices between highly arousing, negative images and positive or negative alternatives. The negative images displayed social scenes that involved death, violence or harm (e.g., war scene), or decontextualized, close-ups of physical harm (e.g., mutilated face) or natural threat (e.g., attacking shark). The results demonstrated that social negative images were chosen significantly more often than other negative categories. Furthermore, participants preferred social negative images over neutral images. Physical harm images and natural threat images were not preferred over neutral images, but were chosen in about thirty-five percent of the trials. These results were replicated across three different studies, including a study that presented verbal descriptions of images as pre-choice cues. Together, these results show that people deliberately subject themselves to negative images. With this, the present paper demonstrates a dynamic relationship between negative information and behavior and advances new insights into the phenomenon of morbid curiosity. [ABSTRACT FROM AUTHOR]

The Million Dollar List (MDL, online at ) is a compilation of publicly announced charitable donations of $1 million or more from across the United States since 2000; as of December 2016, the database contains close to 80,000 gifts made by U.S. individuals, corporations, foundations, and other grant-making nonprofit organizations. This paper discusses the unique value of the Million Dollar List and provides unique insights to key questions such as: How does distance affect giving? How do networks impact million-dollar-plus gifts? Understanding the geospatial and temporal dimensions of philanthropy can assist researchers and policymakers to better understand the role of private funding in innovation and discovery. Moreover, the results from the paper emphasize the importance of philanthropy for fueling research and development in science, the arts, environment, and health. The paper also includes the limitations of the presented analyses and promising future work. [ABSTRACT FROM AUTHOR]