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Background: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. Objectives: This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. Methods: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. Results: FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The “signal” in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. Conclusion: There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias). [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10−14), even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner’s Curse (p < 10−16). We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94). In contrast, ancestry differences between replication and discovery (13 studies, 385 loci) cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium. [ABSTRACT FROM AUTHOR]

From January 2014, Psychological Science introduced new submission guidelines that encouraged the use of effect sizes, estimation, and meta-analysis (the “new statistics”), required extra detail of methods, and offered badges for use of open science practices. We investigated the use of these practices in empirical articles published by Psychological Science and, for comparison, by the Journal of Experimental Psychology: General, during the period of January 2013 to December 2015. The use of null hypothesis significance testing (NHST) was extremely high at all times and in both journals. In Psychological Science, the use of confidence intervals increased markedly overall, from 28% of articles in 2013 to 70% in 2015, as did the availability of open data (3 to 39%) and open materials (7 to 31%). The other journal showed smaller or much smaller changes. Our findings suggest that journal-specific submission guidelines may encourage desirable changes in authors’ practices. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

Traffic congestion is an important problem both on an individual and on a societal level and much research has been done to explain and prevent their emergence. There are currently many systems which provide a reasonably good picture of actual road traffic by employing either fixed measurement points on highways or so called “floating car data” i.e. by using velocity and location data from roaming, networked, GPS enabled members of traffic. Some of these systems also offer forecasting of road conditions based on such historical data. To my knowledge there is as yet no system which offers advance notice on road conditions based on a signal which is guaranteed to occur in advance of these conditions and this is the novelty of this paper. Google Search intensity for the German word (i.e. traffic jam) peaks 2 hours ahead of the number of traffic jam reports as reported by the ADAC, a well known German automobile club and the largest of its kind in Europe. This is true both in the morning (7 am to 9 am) and in the evening (4 pm to 6 pm). The main result of this paper is then that after controlling for time-of-day and day-of-week effects we can still explain a significant additional portion of the variation of the number of traffic jam reports with Google Trends and we can thus explain well over 80% of the variation of road conditions using Google search activity. A one percent increase in Google stau searches implies a .4 percent increase of traffic jams. Our paper is a proof of concept that aggregate, timely delivered behavioural data can help fine tune modern societies and prompts for more research with better, more disaggregated data in order to also achieve practical solutions. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a step-stress partially accelerated lifetime test for the four-component hybrid systems with Type-II progressive hybrid censoring scheme while the life time of system component follows exponential failure rate. In many cases, the exact component causing the system failure cannot be identified and the cause of failure is masked. Based on Type-II progressively hybrid censored and masked data, the maximum likelihood estimations for unknown parameters and acceleration factor are obtained. In addition, approximate confidence interval and bootstrap confidence interval are presented by using the asymptotic distributions of the maximum likelihood estimations for unknown parameters and bootstrap method, respectively. Finally, the proposed method is illustrated through the simulation studies. [ABSTRACT FROM AUTHOR]

A working group established in the framework of the EUPHRESCO European collaborative project aimed to compare and validate diagnostic protocols for the detection of “Flavescence dorée” (FD) phytoplasma in grapevines. Seven molecular protocols were compared in an interlaboratory test performance study where each laboratory had to analyze the same panel of samples consisting of DNA extracts prepared by the organizing laboratory. The tested molecular methods consisted of universal and group-specific real-time and end-point nested PCR tests. Different statistical approaches were applied to this collaborative study. Firstly, there was the standard statistical approach consisting in analyzing samples which are known to be positive and samples which are known to be negative and reporting the proportion of false-positive and false-negative results to respectively calculate diagnostic specificity and sensitivity. This approach was supplemented by the calculation of repeatability and reproducibility for qualitative methods based on the notions of accordance and concordance. Other new approaches were also implemented, based, on the one hand, on the probability of detection model, and, on the other hand, on Bayes’ theorem. These various statistical approaches are complementary and give consistent results. Their combination, and in particular, the introduction of new statistical approaches give overall information on the performance and limitations of the different methods, and are particularly useful for selecting the most appropriate detection scheme with regards to the prevalence of the pathogen. Three real-time PCR protocols (methods M4, M5 and M6 respectively developed by Hren (2007), Pelletier (2009) and under patent oligonucleotides) achieved the highest levels of performance for FD phytoplasma detection. This paper also addresses the issue of indeterminate results and the identification of outlier results. The statistical tools presented in this paper and their combination can be applied to many other studies concerning plant pathogens and other disciplines that use qualitative detection methods. [ABSTRACT FROM AUTHOR]

Knowledge of contagion among economies is a relevant issue in economics. The canonical model of contagion is an alternative in this case. Given the existence of endogenous variables in the model, instrumental variables can be used to decrease the bias of the OLS estimator. In the presence of heteroskedastic disturbances this paper proposes the use of conditional volatilities as instruments. Simulation is used to show that the homoscedastic and heteroskedastic estimators which use them as instruments have small bias. These estimators are preferable in comparison with the OLS estimator and their asymptotic distribution can be used to construct confidence intervals. [ABSTRACT FROM AUTHOR]

Background: Exaggerated or simplistic news is often blamed for adversely influencing public health. However, recent findings suggested many exaggerations were already present in university press releases, which scientists approve. Surprisingly, these exaggerations were not associated with more news coverage. Here we test whether these two controversial results also arise in press releases from prominent science and medical journals. We then investigate the influence of mitigating caveats in press releases, to test assumptions that caveats harm news interest or are ignored. Methods and Findings: Using quantitative content analysis, we analyzed press releases (N = 534) on biomedical and health-related science issued by leading peer-reviewed journals. We similarly analysed the associated peer-reviewed papers (N = 534) and news stories (N = 582). Main outcome measures were advice to readers and causal statements drawn from correlational research. Exaggerations in press releases predicted exaggerations in news (odds ratios 2.4 and 10.9, 95% CIs 1.3 to 4.5 and 3.9 to 30.1) but were not associated with increased news coverage, consistent with previous findings. Combining datasets from universities and journals (996 press releases, 1250 news), we found that when caveats appeared in press releases there was no reduction in journalistic uptake, but there was a clear increase in caveats in news (odds ratios 9.6 and 9.5 for caveats for advice and causal claims, CIs 4.1 to 24.3 and 6.0 to 15.2). The main study limitation is its retrospective correlational nature. Conclusions: For health and science news directly inspired by press releases, the main source of both exaggerations and caveats appears to be the press release itself. However we find no evidence that exaggerations increase, or caveats decrease, the likelihood of news coverage. These findings should be encouraging for press officers and scientists who wish to minimise exaggeration and include caveats in their press releases. [ABSTRACT FROM AUTHOR]

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder’s theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods: Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results: A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion: The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria. [ABSTRACT FROM AUTHOR]

Sample sizes for randomized controlled trials are typically based on power calculations. They require us to specify values for parameters such as the treatment effect, which is often difficult because we lack sufficient prior information. The objective of this paper is to provide an alternative design which circumvents the need for sample size calculation. In a simulation study, we compared a meta-experiment approach to the classical approach to assess treatment efficacy. The meta-experiment approach involves use of meta-analyzed results from 3 randomized trials of fixed sample size, 100 subjects. The classical approach involves a single randomized trial with the sample size calculated on the basis of an a priori-formulated hypothesis. For the sample size calculation in the classical approach, we used observed articles to characterize errors made on the formulated hypothesis. A prospective meta-analysis of data from trials of fixed sample size provided the same precision, power and type I error rate, on average, as the classical approach. The meta-experiment approach may provide an alternative design which does not require a sample size calculation and addresses the essential need for study replication; results may have greater external validity. [ABSTRACT FROM AUTHOR]

The aim of this paper is to provide a Bayesian formulation of the so-called magnitude-based inference approach to quantifying and interpreting effects, and in a case study example provide accurate probabilistic statements that correspond to the intended magnitude-based inferences. The model is described in the context of a published small-scale athlete study which employed a magnitude-based inference approach to compare the effect of two altitude training regimens (live high-train low (LHTL), and intermittent hypoxic exposure (IHE)) on running performance and blood measurements of elite triathletes. The posterior distributions, and corresponding point and interval estimates, for the parameters and associated effects and comparisons of interest, were estimated using Markov chain Monte Carlo simulations. The Bayesian analysis was shown to provide more direct probabilistic comparisons of treatments and able to identify small effects of interest. The approach avoided asymptotic assumptions and overcame issues such as multiple testing. Bayesian analysis of unscaled effects showed a probability of 0.96 that LHTL yields a substantially greater increase in hemoglobin mass than IHE, a 0.93 probability of a substantially greater improvement in running economy and a greater than 0.96 probability that both IHE and LHTL yield a substantially greater improvement in maximum blood lactate concentration compared to a Placebo. The conclusions are consistent with those obtained using a ‘magnitude-based inference’ approach that has been promoted in the field. The paper demonstrates that a fully Bayesian analysis is a simple and effective way of analysing small effects, providing a rich set of results that are straightforward to interpret in terms of probabilistic statements. [ABSTRACT FROM AUTHOR]

The present paper examines the relation between size, accumulation and performance for research grants, where we examine the relation between grant size for Centres of Excellence (CoE) funded by the Danish National Research Foundation (DNRF) and various ex post research performance measures, including impact and shares of highly cited articles. We examine both the relation between size and performance and also how performance for CoEs evolves over the course of grant periods. In terms of dynamics, it appears that performance over the grant period (i.e. 10 years) is falling for the largest CoEs, while it is increasing for those among the smallest half. Overall, multivariate econometric analysis finds evidence that performance is increasing in grant size and over time. In both cases, the relation appears to be non-linear, suggesting that there is a point at which performance peaks. The CoEs have also been very successful in securing additional funding, which can be viewed as a ‘cumulative effect’ of center grants. In terms of new personnel, the far majority of additional funding is spent on early career researchers, hence, this accumulation would appear to have a ‘generational’ dimension, allowing for scientific expertise to be passed on to an increasing number of younger researchers. [ABSTRACT FROM AUTHOR]

Often, the reader of a published paper is interested in a comparison of parameters that has not been presented. It is not possible to make inferences beyond point estimation since the standard error for the contrast of the estimated parameters depends upon the (unreported) correlation. This study explores approaches to obtain valid confidence intervals when the correlation is unknown. We illustrate three proposed approaches using data from the National Health Interview Survey. The three approaches include the Bonferroni method and the standard confidence interval assuming (most conservative) or (when the correlation is known to be non-negative). The Bonferroni approach is found to be the most conservative. For the difference in two estimated parameter, the standard confidence interval assuming yields a 95% confidence interval that is approximately 12.5% narrower than the Bonferroni confidence interval; when the correlation is known to be positive, the standard 95% confidence interval assuming is approximately 38% narrower than the Bonferroni. In summary, this article demonstrates simple methods to determine confidence intervals for unreported comparisons. We suggest use of the standard confidence interval assuming if no information is available or if the correlation is known to be non-negative. [ABSTRACT FROM AUTHOR]

Long-term social security statistical forecasts produced and disseminated by the Brazilian government aim to provide accurate results that would serve as background information for optimal policy decisions. These forecasts are being used as support for the government’s proposed pension reform that plans to radically change the Brazilian Constitution insofar as Social Security is concerned. However, the reliability of official results is uncertain since no systematic evaluation of these forecasts has ever been published by the Brazilian government or anyone else. This paper aims to present a study of the accuracy and methodology of the instruments used by the Brazilian government to carry out long-term actuarial forecasts. We base our research on an empirical and probabilistic analysis of the official models. Our empirical analysis shows that the long-term Social Security forecasts are systematically biased in the short term and have significant errors that render them meaningless in the long run. Moreover, the low level of transparency in the methods impaired the replication of results published by the Brazilian Government and the use of outdated data compromises forecast results. In the theoretical analysis, based on a mathematical modeling approach, we discuss the complexity and limitations of the macroeconomic forecast through the computation of confidence intervals. We demonstrate the problems related to error measurement inherent to any forecasting process. We then extend this exercise to the computation of confidence intervals for Social Security forecasts. This mathematical exercise raises questions about the degree of reliability of the Social Security forecasts. [ABSTRACT FROM AUTHOR]

A new head pose estimation technique based on Random Forest (RF) and texture features for facial image analysis using a monocular camera is proposed in this paper, especially about how to efficiently combine the random forest and the features. In the proposed technique a randomized tree with useful attributes is trained to improve estimation accuracy and tolerance of occlusions and illumination. Specifically, a number of features including Multi-scale Block Local Block Pattern (MB-LBP) are extracted from an image, and random features such as the MB-LBP scale parameters, a block coordinate, and a layer of an image pyramid in the feature pool are used for training the tree. The randomized tree aims to maximize the information gain at each node while random samples traverse the nodes in the tree. To this aim, a split function considering the uniform property of the LBP feature is developed to move sample blocks to the left or the right children nodes. The trees are independently trained with random inputs, yet they are grouped to form a random forest so that the results collected from the trees are used for make the final decision. Precisely, we use a Maximum-A-Posteriori criterion in the decision. It is demonstrated with experimental results that the proposed technique provides significantly enhanced classification performance in the head pose estimation in various conditions of illumination, poses, expressions, and facial occlusions. [ABSTRACT FROM AUTHOR]

The estimation of the correct number of dimensions is a long-standing problem in psychometrics. Several methods have been proposed, such as parallel analysis (PA), Kaiser-Guttman’s eigenvalue-greater-than-one rule, multiple average partial procedure (MAP), the maximum-likelihood approaches that use fit indexes as BIC and EBIC and the less used and studied approach called very simple structure (VSS). In the present paper a new approach to estimate the number of dimensions will be introduced and compared via simulation to the traditional techniques pointed above. The approach proposed in the current paper is called exploratory graph analysis (EGA), since it is based on the graphical lasso with the regularization parameter specified using EBIC. The number of dimensions is verified using the walktrap, a random walk algorithm used to identify communities in networks. In total, 32,000 data sets were simulated to fit known factor structures, with the data sets varying across different criteria: number of factors (2 and 4), number of items (5 and 10), sample size (100, 500, 1000 and 5000) and correlation between factors (orthogonal, .20, .50 and .70), resulting in 64 different conditions. For each condition, 500 data sets were simulated using lavaan. The result shows that the EGA performs comparable to parallel analysis, EBIC, eBIC and to Kaiser-Guttman rule in a number of situations, especially when the number of factors was two. However, EGA was the only technique able to correctly estimate the number of dimensions in the four-factor structure when the correlation between factors were .7, showing an accuracy of 100% for a sample size of 5,000 observations. Finally, the EGA was used to estimate the number of factors in a real dataset, in order to compare its performance with the other six techniques tested in the simulation study. [ABSTRACT FROM AUTHOR]

In epidemiological studies, exposures of interest are often measured with uncertainties, which may be independent or correlated. Independent errors can often be characterized relatively easily while correlated measurement errors have shared and hierarchical components that complicate the description of their structure. For some important studies, Monte Carlo dosimetry systems that provide multiple realizations of exposure estimates have been used to represent such complex error structures. While the effects of independent measurement errors on parameter estimation and methods to correct these effects have been studied comprehensively in the epidemiological literature, the literature on the effects of correlated errors, and associated correction methods is much more sparse. In this paper, we implement a novel method that calculates corrected confidence intervals based on the approximate asymptotic distribution of parameter estimates in linear excess relative risk (ERR) models. These models are widely used in survival analysis, particularly in radiation epidemiology. Specifically, for the dose effect estimate of interest (increase in relative risk per unit dose), a mixture distribution consisting of a normal and a lognormal component is applied. This choice of asymptotic approximation guarantees that corrected confidence intervals will always be bounded, a result which does not hold under a normal approximation. A simulation study was conducted to evaluate the proposed method in survival analysis using a realistic ERR model. We used both simulated Monte Carlo dosimetry systems (MCDS) and actual dose histories from the Mayak Worker Dosimetry System 2013, a MCDS for plutonium exposures in the Mayak Worker Cohort. Results show our proposed methods provide much improved coverage probabilities for the dose effect parameter, and noticeable improvements for other model parameters. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) protocol are well established in many surgical disciplines, leading to decrease in morbidity and length of hospital stay. These multi-modal protocols have been also introduced to oesophageal cancer surgery. This review aimed to evaluate current literature on ERAS in oesophageal cancer surgery and conduct a meta-analysis on primary and secondary outcomes. Methods: MEDLINE, Embase, Scopus and Cochrane Library were searched for eligible studies. We analyzed data up to May 2016. Eligible studies had to contain four described ERAS protocol elements. The primary outcome was overall morbidity. Secondary outcomes included length of hospital stay, specific complications, mortality and readmissions. Random effect meta-analyses were undertaken. Results: Initial search yielded 1,064 articles. Thorough evaluation resulted in 13 eligible articles which were analyzed. A total of 2,042 patients were included in the analysis (1,058 ERAS group and 984 treated with traditional protocols). Analysis of overall morbidity as well as complication rate did not show any significant reduction. Non-surgical complications and pulmonary complications were significantly lower in the ERAS group, RR = 0.71 95% CI 0.62–0.80, p < 0.00001 and RR = 0.75, 95% CI 0.60–0.94, p = 0.01, respectively. Meta-analysis on length of stay presented significant reduction Mean difference = -3.55, 95% CI -4.41 to -2.69, p for effect<0.00001. Conclusions: This systematic review with a meta-analysis on ERAS in oesophageal surgery indicates a reduction of non-surgical complications and no negative influence on overall morbidity. Moreover, a reduction in the length of hospital stay was presented. [ABSTRACT FROM AUTHOR]

Background: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. Methodology/Principal findings: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. Conclusions/Significance: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood. [ABSTRACT FROM AUTHOR]

Historically, admissions committees for biomedical Ph.D. programs have heavily weighed GRE scores when considering applications for admission. The predictive validity of GRE scores on graduate student success is unclear, and there have been no recent investigations specifically on the relationship between general GRE scores and graduate student success in biomedical research. Data from Vanderbilt University Medical School’s biomedical umbrella program were used to test to what extent GRE scores can predict outcomes in graduate school training when controlling for other admissions information. Overall, the GRE did not prove useful in predicating who will graduate with a Ph.D., pass the qualifying exam, have a shorter time to defense, deliver more conference presentations, publish more first author papers, or obtain an individual grant or fellowship. GRE scores were found to be moderate predictors of first semester grades, and weak to moderate predictors of graduate GPA and some elements of a faculty evaluation. These findings suggest admissions committees of biomedical doctoral programs should consider minimizing their reliance on GRE scores to predict the important measures of progress in the program and student productivity. [ABSTRACT FROM AUTHOR]

Background: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions.Methods and Findings: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014-2015), one WHO dataset (2015), and three RNTCP reports (2014-2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000-2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB-including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000-3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775-1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival. The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India.Conclusions: Increasing case detection is critical to improving outcomes in India's TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India. [ABSTRACT FROM AUTHOR]

A challenge when interpreting replications is determining whether the results of a replication “successfully” replicate the original study. Looking for consistency between two studies is challenging because individual studies are susceptible to many sources of error that can cause study results to deviate from each other and the population effect in unpredictable directions and magnitudes. In the current paper, we derive methods to compute a prediction interval, a range of results that can be expected in a replication due to chance (i.e., sampling error), for means and commonly used indexes of effect size: correlations and d-values. The prediction interval is calculable based on objective study characteristics (i.e., effect size of the original study and sample sizes of the original study and planned replication) even when sample sizes across studies are unequal. The prediction interval provides an a priori method for assessing if the difference between an original and replication result is consistent with what can be expected due to sample error alone. We provide open-source software tools that allow researchers, reviewers, replicators, and editors to easily calculate prediction intervals. [ABSTRACT FROM AUTHOR]

The remaining useful life (RUL) prediction of Lithium-ion batteries is closely related to the capacity degeneration trajectories. Due to the self-charging and the capacity regeneration, the trajectories have the property of multimodality. Traditional prediction models such as the support vector machines (SVM) or the Gaussian Process regression (GPR) cannot accurately characterize this multimodality. This paper proposes a novel RUL prediction method based on the Gaussian Process Mixture (GPM). It can process multimodality by fitting different segments of trajectories with different GPR models separately, such that the tiny differences among these segments can be revealed. The method is demonstrated to be effective for prediction by the excellent predictive result of the experiments on the two commercial and chargeable Type 1850 Lithium-ion batteries, provided by NASA. The performance comparison among the models illustrates that the GPM is more accurate than the SVM and the GPR. In addition, GPM can yield the predictive confidence interval, which makes the prediction more reliable than that of traditional models. [ABSTRACT FROM AUTHOR]

Background: Role substitution is a strategy employed to assist health services manage the growing demand for musculoskeletal care. Corticosteroid injection is a common treatment in this population but the efficacy of its prescription and delivery by physiotherapists has not been established against orthopaedic standards. This paper investigates whether corticosteroid injection given by a physiotherapist for shoulder pain is as clinically and cost effective as that from an orthopaedic surgeon. Methods: A double blind non-inferiority randomized controlled trial was conducted in an Australian public hospital orthopaedic outpatient service, from January 2013 to June 2014. Adults with a General Practitioner referral to Orthopaedics for shoulder pain received subacromial corticosteroid and local anaesthetic injection prescribed and delivered independently by a physiotherapist or a consultant orthopaedic surgeon. The main outcome measure was total Shoulder Pain and Disability Index (SPADI) score at baseline, six and 12 weeks, applying a non-inferiority margin of 15 points. Secondary outcomes tested for superiority included pain, shoulder movement, perceived improvement, adverse events, satisfaction, quality of life and costs. Results: 278 participants were independently assessed by the physiotherapist and the orthopaedic surgeon, with 64 randomised (physiotherapist 33, orthopaedic surgeon 31). There were no significant differences in baseline characteristics between groups. Non-inferiority of injection by the physiotherapist was declared from total SPADI scores at 6 and 12 weeks (upper limit of the 95% one-sided confidence interval 13.34 and 7.17 at 6 and 12 weeks, respectively). There were no statistically significant differences between groups on any outcome measures at 6 or 12 weeks. From the perspective of the health funder, the physiotherapist was less expensive. Conclusions: Corticosteroid injection for shoulder pain, provided by a suitably qualified physiotherapist is at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care. Trial Registration: Australia and New Zealand Clinical Trials Registry [ABSTRACT FROM AUTHOR]

Kinks are a structural feature of alpha-helices and many are known to have functional roles. Kinks have previously tended to be defined in a binary fashion. In this paper we have deliberately moved towards defining them on a continuum, which given the unimodal distribution of kink angles is a better description. From this perspective, we examine the conservation of kinks in proteins. We find that kink angles are not generally a conserved property of homologs, pointing either to their not being functionally critical or to their function being related to conformational flexibility. In the latter case, the different structures of homologs are providing snapshots of different conformations. Sequence identity between homologous helices is informative in terms of kink conservation, but almost equally so is the sequence identity of residues in spatial proximity to the kink. In the specific case of proline, which is known to be prevalent in kinked helices, loss of a proline from a kinked helix often also results in the loss of a kink or reduction in its kink angle. We carried out a study of the seven transmembrane helices in the GPCR family and found that changes in kinks could be related both to subfamilies of GPCRs and also, in a particular subfamily, to the binding of agonists or antagonists. These results suggest conformational change upon receptor activation within the GPCR family. We also found correlation between kink angles in different helices, and the possibility of concerted motion could be investigated further by applying our method to molecular dynamics simulations. These observations reinforce the belief that helix kinks are key, functional, flexible points in structures. [ABSTRACT FROM AUTHOR]

Rainy weather conditions could result in significantly negative impacts on driving on freeways. However, due to lack of enough historical data and monitoring facilities, many regions are not able to establish reliable risk assessment models to identify such impacts. Given the situation, this paper provides an alternative solution where the procedure of risk assessment is developed based on drivers’ subjective questionnaire and its performance is validated by using actual crash data. First, an ordered logit model was developed, based on questionnaire data collected from Freeway G15 in China, to estimate the relationship between drivers’ perceived risk and factors, including vehicle type, rain intensity, traffic volume, and location. Then, weighted driving risk for different conditions was obtained by the model, and further divided into four levels of early warning (specified by colors) using a rank order cluster analysis. After that, a risk matrix was established to determine which warning color should be disseminated to drivers, given a specific condition. Finally, to validate the proposed procedure, actual crash data from Freeway G15 were compared with the safety prediction based on the risk matrix. The results show that the risk matrix obtained in the study is able to predict driving risk consistent with actual safety implications, under rainy weather conditions. [ABSTRACT FROM AUTHOR]

Distribution function estimation of the random variable of river flow is an important problem in hydrology. This issue is directly related to quantile estimation, and consequently to return level prediction. The estimation process can be complemented with the construction of confidence intervals (CIs) to perform a probabilistic assessment of the different variables and/or estimated functions. In this work, several methods for constructing CIs using bootstrap techniques, and parametric and nonparametric procedures in the estimation process are studied and compared. In the case that the target is the joint estimation of a vector of values, some new corrections to obtain joint coverage probabilities closer to the corresponding nominal values are also presented. A comprehensive simulation study compares the different approaches, and the application of the different procedures to real data sets from four rivers in the United States and one in Spain complete the paper. [ABSTRACT FROM AUTHOR]

In this paper we propose an instrument for collecting sensitive data that allows for each participant to customize the amount of information that she is comfortable revealing. Current methods adopt a uniform approach where all subjects are afforded the same privacy guarantees; however, privacy is a highly subjective property with intermediate points between total disclosure and non-disclosure: each respondent has a different criterion regarding the sensitivity of a particular topic. The method we propose empowers respondents in this respect while still allowing for the discovery of interesting findings through the application of well-known inferential procedures. [ABSTRACT FROM AUTHOR]

Objectives: To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). Methods: We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Results: Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83–4.09, P = 0.006; WMD 13.10, 95% CI 9.53–16.67, P < 0.001; WMD 14.34, 95% CI 10.26–18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06–3.18, P = 0.027; WMD 5.63, 95% CI 2.74–8.52, P < 0.001; WMD 3.30, 95% CI 2.10–4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). Conclusions: IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF. [ABSTRACT FROM AUTHOR]

Background: In a recent individual patient data meta-analysis, acupuncture was found to be superior to both sham and non-sham controls in patients with chronic pain. In this paper we identify variations in types of sham and non-sham controls used and analyze their impact on the effect size of acupuncture. Methods: Based on literature searches of acupuncture trials involving patients with headache and migraine, osteoarthritis, and back, neck and shoulder pain, 29 trials met inclusion criteria, 20 involving sham controls (n = 5,230) and 18 non-sham controls (n = 14,597). For sham controls, we analysed non-needle sham, penetrating sham needles and non-penetrating sham needles. For non-sham controls, we analysed non-specified routine care and protocol-guided care. Using meta-regression we explored impact of choice of control on effect of acupuncture. Findings: Acupuncture was significantly superior to all categories of control group. For trials that used penetrating needles for sham control, acupuncture had smaller effect sizes than for trials with non-penetrating sham or sham control without needles. The difference in effect size was −0.45 (95% C.I. −0.78, −0.12; p = 0.007), or −0.19 (95% C.I. −0.39, 0.01; p = 0.058) after exclusion of outlying studies showing very large effects of acupuncture. In trials with non-sham controls, larger effect sizes associated with acupuncture vs. non-specified routine care than vs. protocol-guided care. Although the difference in effect size was large (0.26), it was not significant with a wide confidence interval (95% C.I. −0.05, 0.57, p = 0.1). Conclusion: Acupuncture is significantly superior to control irrespective of the subtype of control. While the choice of control should be driven by the study question, our findings can help inform study design in acupuncture, particularly with respect to sample size. Penetrating needles appear to have important physiologic activity. We recommend that this type of sham be avoided. [ABSTRACT FROM AUTHOR]

P values represent a widely used, but pervasively misunderstood and fiercely contested method of scientific inference. Display items, such as figures and tables, often containing the main results, are an important source of P values. We conducted a survey comparing the overall use of P values and the occurrence of significant P values in display items of a sample of articles in the three top multidisciplinary journals (Nature, Science, PNAS) in 2017 and, respectively, in 1997. We also examined the reporting of multiplicity corrections and its potential influence on the proportion of statistically significant P values. Our findings demonstrated substantial and growing reliance on P values in display items, with increases of 2.5 to 14.5 times in 2017 compared to 1997. The overwhelming majority of P values (94%, 95% confidence interval [CI] 92% to 96%) were statistically significant. Methods to adjust for multiplicity were almost non-existent in 1997, but reported in many articles relying on P values in 2017 (Nature 68%, Science 48%, PNAS 38%). In their absence, almost all reported P values were statistically significant (98%, 95% CI 96% to 99%). Conversely, when any multiplicity corrections were described, 88% (95% CI 82% to 93%) of reported P values were statistically significant. Use of Bayesian methods was scant (2.5%) and rarely (0.7%) articles relied exclusively on Bayesian statistics. Overall, wider appreciation of the need for multiplicity corrections is a welcome evolution, but the rapid growth of reliance on P values and implausibly high rates of reported statistical significance are worrisome. [ABSTRACT FROM AUTHOR]

Appropriate large-scale citizen-science data present important new opportunities for biodiversity modelling, due in part to the wide spatial coverage of information. Recently proposed occupancy modelling approaches naturally incorporate random effects in order to account for annual variation in the composition of sites surveyed. In turn this leads to Bayesian analysis and model fitting, which are typically extremely time consuming. Motivated by presence-only records of occurrence from the UK Butterflies for the New Millennium data base, we present an alternative approach, in which site variation is described in a standard way through logistic regression on relevant environmental covariates. This allows efficient occupancy model-fitting using classical inference, which is easily achieved using standard computers. This is especially important when models need to be fitted each year, typically for many different species, as with British butterflies for example. Using both real and simulated data we demonstrate that the two approaches, with and without random effects, can result in similar conclusions regarding trends. There are many advantages to classical model-fitting, including the ability to compare a range of alternative models, identify appropriate covariates and assess model fit, using standard tools of maximum likelihood. In addition, modelling in terms of covariates provides opportunities for understanding the ecological processes that are in operation. We show that there is even greater potential; the classical approach allows us to construct regional indices simply, which indicate how changes in occupancy typically vary over a species’ range. In addition we are also able to construct dynamic occupancy maps, which provide a novel, modern tool for examining temporal changes in species distribution. These new developments may be applied to a wide range of taxa, and are valuable at a time of climate change. They also have the potential to motivate citizen scientists. [ABSTRACT FROM AUTHOR]

With a more Internet-savvy and sophisticated user base, there are more demands for interactive applications and services. However, it is a challenge for existing radio access networks (e.g. 3G and 4G) to cope with the increasingly demanding requirements such as higher data rates and wider coverage area. One potential solution is the inter-collaborative deployment of multiple radio devices in a 5G setting designed to meet exacting user demands, and facilitate the high data rate requirements in the underlying networks. These heterogeneous 5G networks can readily resolve the data rate and coverage challenges. Networks established using the hybridization of existing networks have diverse military and civilian applications. However, there are inherent limitations in such networks such as irregular breakdown, node failures, and halts during speed transmissions. In recent years, there have been attempts to integrate heterogeneous 5G networks with existing ad hoc networks to provide a robust solution for delay-tolerant transmissions in the form of packet switched networks. However, continuous connectivity is still required in these networks, in order to efficiently regulate the flow to allow the formation of a robust network. Therefore, in this paper, we present a novel network formation consisting of nodes from different network maneuvered by Unmanned Aircraft (UA). The proposed model utilizes the features of a biological aspect of genomes and forms a delay tolerant network with existing network models. This allows us to provide continuous and robust connectivity. We then demonstrate that the proposed network model has an efficient data delivery, lower overheads and lesser delays with high convergence rate in comparison to existing approaches, based on evaluations in both real-time testbed and simulation environment. [ABSTRACT FROM AUTHOR]

Background: We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events.Methods and Findings: Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published.Conclusions: There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events. [ABSTRACT FROM AUTHOR]

Inhibin B has been identified as a potential marker of Sertoli cell function in males. The aim of this study is to produce a normative model of serum inhibin B in males from birth to seventeen years. We used a well-defined search strategy to identify studies containing data that can contribute to a larger approximation of the healthy population. We combined data from four published studies (n = 709) and derived an internally validated model with high goodness-of-fit and normally distributed residuals. Our results show that inhibin B increases following birth to a post-natal peak of 270 pg/mL (IQR 210–335 pg/mL) and then decreases during childhood followed by a rise at around 8 years, peaking at a mean 305 pg/mL (IQR 240–445 pg/mL) at around age 17. Following this peak there is a slow decline to the standard mature adult normal range of 170 pg/mL (IQR 125–215 pg/mL). This normative model suggests that 35% of the variation in Inhibin B levels in young males is due to age alone, provides an age-specific reference range for inhibin B in the young healthy male population, and will be a powerful tool in evaluating the potential of inhibin B as a marker of Sertoli cell function in pre-pubertal boys. [ABSTRACT FROM AUTHOR]

Optical Music Recognition (OMR) has received increasing attention in recent years. In this paper, we propose a classifier based on a new method named Directed Acyclic Graph-Large margin Distribution Machine (DAG-LDM). The DAG-LDM is an improvement of the Large margin Distribution Machine (LDM), which is a binary classifier that optimizes the margin distribution by maximizing the margin mean and minimizing the margin variance simultaneously. We modify the LDM to the DAG-LDM to solve the multi-class music symbol classification problem. Tests are conducted on more than 10000 music symbol images, obtained from handwritten and printed images of music scores. The proposed method provides superior classification capability and achieves much higher classification accuracy than the state-of-the-art algorithms such as Support Vector Machines (SVMs) and Neural Networks (NNs). [ABSTRACT FROM AUTHOR]

Health disparities are commonplace and of broad interest to policy makers, but are also challenging to measure and communicate. The Health Disparity Calculator software (HD*Calc, v1.2.4) offers Monte Carlo simulation (MCS)-based confidence interval (CI) estimation of eleven disparity measures. The MCS approach provides accurate CI estimation, except when data are scarce (e.g., rare cancers). To address sparse data challenges to CI estimation, we propose two solutions: 1) employing the gamma distribution in the MCS and 2) utilizing a zero-inflated Poisson estimate for Poisson sampling in simulation experiments. We evaluate each solution through simulation studies using female breast, female brain, lung, and cervical cancer data from the Surveillance, Epidemiology, and End Results (SEER) program. We compare the coverage probabilities (CPs) of eleven health disparity measures based on simulated datasets. The truncated normal distribution implemented in the MCS with the standard Poisson samples (the default setting of HD*Calc) leads to less-than-optimal coverage probabilities (<95%). When both the gamma distribution and the estimated mean from the zero-inflated Poisson are used for the MCS, the coverage probabilities are close to the nominal level of 95%. Simulation studies also demonstrate that collapsing age categories for better CI estimation is not a pragmatic solution. [ABSTRACT FROM AUTHOR]

Background: Changes in head and neck position may significantly affect the performance of supraglottic airway devices (SADs) by altering the pharyngeal structure. Purpose: This systematic review and meta-analysis aimed to elucidate the effect of changes in head and neck position on performance of SADs. Data source: Bibliographic databases, including PubMed, EMBASE, the Cochrane library, and the Web of Science. Study eligibility criteria: Prospective studies investigating the effects of head and neck positions on the performance of SADs. Methods: A random effect model was applied in the all analyses. Subgroup analysis was performed according to the type of device and the age of patient. The oropharyngeal leak pressure was the primary outcome measure. Secondary outcome measures included peak inspiratory pressure, fibreoptic view, and ventilation score (PROSPERO, CRD42017076971). Results: Seventeen studies met the eligibility criteria. Overall, the oropharyngeal leak pressure significantly increased (mean difference 4.07 cmH2O; 95% confidence interval 3.30 to 4.84) during neck flexion with adverse effects on ventilation and fibreoptic view. Conversely, the oropharyngeal leak pressure decreased (mean difference −4.05; 95% confidence interval −4.90 to −3.20) during neck extension with no significant effect on ventilation or fibreoptic view. Rotation of the head and neck did not significantly affect SAD performance. Conclusions: The reduced oropharyngeal leak pressure in the extended neck position was not associated with impaired ventilation except with the air-Q self-pressurizing airway. The flexed neck position significantly worsens ventilation and the alignment between the SAD and glottis despite improving the seal except with the air-Q self-pressurizing airway and LMA Proseal. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the relationship between pet ownership and cardiovascular (CV) outcomes. Methods: We searched the PubMed, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases up to August 2018. Eligible publications examining the association between pet ownership and all-cause and CV mortality (primary outcomes) and risks of cardiovascular disease (CVD), myocardial infarction (MI), and stroke (secondary outcomes) were included. We used the Newcastle–Ottawa Scale to assess the quality of the articles. Results: We included 12 studies, involving 488,986 participants (52.3% female, mean age 56.1 years), in our systematic review. The mean follow-up duration was 8.7 ± 6.3 years. Pet ownership had no association with adjusted all-cause mortality (odds ratio, OR = 1.01, 95% confidence interval, CI [0.94, 1.08], I2 = 76%), adjusted CV mortality (OR = 0.87, 95% CI [0.75, 1.00], I2 = 72%), or risk of cardiovascular disease (CVD) (OR = 0.87, 95% CI [0.72, 1.05], I2 = 73%), myocardial infarction (MI) (OR = 0.99, 95% CI [0.97, 1.01], I2 = 0%), or stroke (OR = 0.99, 95% CI [0.98, 1.01], I2 = 0%). However, subgroup analysis showed that pet ownership was associated with a lower adjusted CV mortality in the general population (OR = 0.93, 95% CI [0.86, 0.99], I2 = 27%) than in CVD patients. In patients with established CVD, pet ownership was associated with a lower adjusted CVD risk (OR = 0.71, 95% CI [0.60, 0.84], I2 = 0%). Conclusion: Pet ownership is not associated with adjusted all-cause or CV mortality, or risk of CVD, MI, or stroke, but it is associated with a lower adjusted CV mortality in the general population and a lower CVD risk in patients with established CVD. [ABSTRACT FROM AUTHOR]

The movement towards open science is a consequence of seemingly pervasive failures to replicate previous research. This transition comes with great benefits but also significant challenges that are likely to affect those who carry out the research, usually early career researchers (ECRs). Here, we describe key benefits, including reputational gains, increased chances of publication, and a broader increase in the reliability of research. The increased chances of publication are supported by exploratory analyses indicating null findings are substantially more likely to be published via open registered reports in comparison to more conventional methods. These benefits are balanced by challenges that we have encountered and that involve increased costs in terms of flexibility, time, and issues with the current incentive structure, all of which seem to affect ECRs acutely. Although there are major obstacles to the early adoption of open science, overall open science practices should benefit both the ECR and improve the quality of research. We review 3 benefits and 3 challenges and provide suggestions from the perspective of ECRs for moving towards open science practices, which we believe scientists and institutions at all levels would do well to consider. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the agreement in percent body fat estimates among 7 laboratory and field assessments against dual-emission x-ray absorptiometry using equivalence testing. Participants were 437 college students (mean age = 19.2±0.6 years). Dual-emission x-ray absorptiometry was used as the criterion with hydrostatic weighing, skinfold thickness, air displacement plethysmography, near infrared reactance, and three methods of bioelectrical impedance analysis examined as surrogate assessments. Relative agreement was examined using intraclass correlation coefficients. Group level agreement was examined using equivalence testing. Individual-level agreement was assessed using Mean Absolute Percent Error and Bland-Altman Plots. Single measure intraclass correlation coefficient scores ranged from 0.71–0.80. Hydrostatic weighing, skinfold thickness, air displacement plethysmography, and 4-electrode bioelectrical impedance analysis showed statistical equivalence with the criterion using a 10% Equivalence Interval with absolute mean differences ranging from 1.0%-4.9% body fat. Mean Absolute Percent Error ranged from 11.7% using skinfold thickness to 21.9% using Omron (hand-held) bioelectrical impedance analysis. Limits of Agreement were heteroscedastic across the range of mean scores compared to dual-emission x-ray absorptiometry, with greater mean differences observed at higher levels of percent body fat. Hydrostatic weighing, skinfold thickness, air displacement plethysmography, and 4-electrode bioelectrical impedance analysis showed strong evidence for statistical equivalence with dual-emission x-ray absorptiometry in a sample of college students. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of thoracic spine manipulation (TSM) on pain and disability in the management of mechanical neck pain (MNP). Data sources: Electronic databases PubMed, CINAHL, Pedro, Embase, AMED, the Cochrane Library, and clinicaltrials.gov were searched in January 2018. Study selection: Eligible studies were completed RCTs, written in English, had at least 2 groups with one group receiving TSM, had at least one measure of pain or disability, and included patients with MNP of any duration. The search identified 1717 potential articles, with 14 studies meeting inclusion criteria. Study appraisal and synthesis methods: Methodological quality was evaluated independently by two authors using the guidelines published by the Cochrane Collaboration. Pooled analyses were analyzed using a random-effects model with inverse variance methods to calculate mean differences (MD) and 95% confidence intervals for pain (VAS 0-100mm, NPRS 0-10pts; 0 = no pain) and disability (NDI and NPQ 0–100%; 0 = no disability). Results: Across the included studies, there was increased risk of bias for inadequate provider and participant blinding. The GRADE approach demonstrated an overall level of evidence ranging from very low to moderate. Meta-analysis that compared TSM to thoracic or cervical mobilization revealed a significant effect favoring the TSM group for pain (MD -13.63; 95% CI: -21.79, -5.46) and disability (MD -9.93; 95% CI: -14.38, -5.48). Meta-analysis that compared TSM to standard care revealed a significant effect favoring the TSM group for pain (MD -13.21; 95% CI: -21.87, -4.55) and disability (MD -11.36; 95% CI: -18.93, -3.78) at short-term follow-up, and a significant effect for disability (MD -4.75; 95% CI: -6.54, -2.95) at long-term follow-up. Meta-analysis that compared TSM to cervical spine manipulation revealed a non-significant effect (MD 3.43; 95% CI: -7.26, 14.11) for pain without a distinction between immediate and short-term follow-up. Limitations: The greatest limitation in this systematic review was the heterogeneity among the studies making it difficult to assess the true clinical benefit, as well as the overall level of quality of evidence. Conclusions: TSM has been shown to be more beneficial than thoracic mobilization, cervical mobilization, and standard care in the short-term, but no better than cervical manipulation or placebo thoracic spine manipulation to improve pain and disability. Trial registration: PROSPERO [ABSTRACT FROM AUTHOR]

Our objective was to examine how exercises with the second generation of the Microsoft Kinect sensor may aid in the process of motor learning in young judo practitioners. We addressed improvements in spatio-temporal accuracy during execution of three standing techniques in judo, in a simple paradigm designed to study short-term practice effects. Two groups of judokas, 12 athletes each—one aided with Kinect and our dedicated software vs a group of controls—were asked to mimic previously recorded master-level performances of the three techniques, established as benchmarks by a two times world champion in judo. In five training sessions, athletes of the aided group used a virtual-reality setup in which they trained with a virtual representation of the master displayed on a large screen with a simultaneous real-time visualisation of their own movements in the form of an avatar based on body joint localisation, as determined by Kinect, which also measured their performance. The control group used Kinect in the 1st and 5th session, which was necessary for the measurements that constituted the basis for subsequent statistical comparisons, whereas the 2nd, 3rd, and 4th session in this group was guided by a coach, without the use of the Kinect setup. In addition, athletes of the two groups had unrestricted access to a video recording of the master performing the three throws. We found statistically significant improvements (p < 0.05) in the accuracy of executing the three techniques between the 1st and the 5th training session for the aided group but not for the control group. We conclude that incorporating Kinect based exercises into a judo training programme may be a useful means to supporting motor learning, therefore enhancing training efficiency, and thus improving performance. [ABSTRACT FROM AUTHOR]

This study was inspired by the need to estimate pointwise confidence intervals (CIs) for a nonlinear dose-response model from a dose-finding clinical trial. Profile likelihood based CI for a nonlinear dose response model is often recommended. However, it is still not commonly used in dose-finding studies because it cannot generally be calculated explicitly. Most previous research has mainly focused on the performance of the profile likelihood based CI method compared with other common approaches. However, there are still no reports on computing profile likelihood based pointwise CIs for an entire dose-response curve. Based on a previous dose-finding trial with binary-response data, this present study proposed to calculate profile likelihood based pointwise CIs by using the bisection method with proper calculation order for doses in the curve plus crude search when the expected response is close to a boundary. The convergence could be improved by applying appropriate starting values for the optimization procedure with straightforward programming techniques. The algorithm worked well in most cases based on the simulation study and it can be applied more generally to other dose-response models, and other type of data like normally distributed response. It would indeed be great to be able to use profile likelihood approaches more routinely when constructing pointwise CIs for nonlinear dose-response models. [ABSTRACT FROM AUTHOR]

Background: Genetics plays a role in determining potential for athletic ability (AA) and sports performance (SP). In this study, AA involves comparing sedentary controls with competitive athletes in power and endurance activities as well as a mix between the two (SP). However, variable results from genetic association studies warrant a meta-analysis to obtain more precise estimates of the association between PPARGC1A Gly482Ser polymorphism and AA/SP. Methods: Multi-database literature search yielded 14 articles (16 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate associations. Summary effects were modified based on statistical power. Subgroup analysis was based on SP (power, endurance and mixed) and race (Caucasians and Asians). Heterogeneity was assessed with the I2 metric and its sources examined with outlier analysis which dichotomized our findings into pre- (PRO) and post-outlier (PSO). Results: Gly allele effects significantly favoring AA/SP (OR > 1.0, P < 0.05) form the core of our findings in: (i) homogeneous overall effect at the post-modified, PSO level (OR 1.13, 95% CI 1.03–1.25, P = 0.01, I2 = 0%); (ii) initially homogeneous power SP (ORs 1.22–1.25, 95% CI 1.05–1.44, P = 0.003–0.008, I2 = 0%) which precluded outlier treatment; (iii) PRO Caucasian outcomes (ORs 1.29–1.32, 95% CI 1.12–1.54, P = 0.0005) over that of Asians with a pooled null effect (OR 0.99, 95% CI 0.72–1.99, P = 0.53–0.92) and (iv) homogeneous all > 80% (ORs 1.19–1.38, 95% CI 1.05–1.66, P = 0.0007–0.007, I2 = 0%) on account of high statistical power (both study-specific and combined). In contrast, none of the Ser allele effects significantly favored AA/SP and no Ser-Gly genotype outcome favored AA/SP. The core significant outcomes were robust and showed no evidence of publication bias. Conclusion: Meta-analytical applications in this study generated evidence that show association between the Gly allele and AA/SP. These were observed in the overall, Caucasians and statistically powered comparisons which exhibited consistent significance, stability, robustness, precision and lack of bias. Our central findings rest on association of the Gly allele with endurance and power, differentially favoring the latter over the former. [ABSTRACT FROM AUTHOR]