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Background Physical inactivity is highly prevalent after stroke, increasing the risk of poor health outcomes including recurrent stroke. Tailoring of exercise programs to individual preferences can improve adherence, but no tools exist for this purpose in stroke. Methods We identified potential questionnaire items for establishing exercise preferences via: (i) our preliminary Exercise Preference Questionnaire in stroke, (ii) similar tools used in other conditions, and (iii) expert panel consultations. The resulting 35-item questionnaire (SEPI-35) was administered to stroke survivors, along with measures of disability, depression, anxiety, fatigue and self-reported physical activity. Exploratory factor analysis was used to identify a factor structure in exercise preferences, providing a framework for item reduction. Associations between exercise preferences and personal characteristics were analysed using multivariable regression. Results A group of 134 community-dwelling stroke survivors (mean age 64.0, SD 13.3) participated. Analysis of the SEPI-35 identified 7 exercise preference factors (Supervision-support, Confidence-challenge, Health-wellbeing, Exercise context, Home-alone, Similar others, Music-TV). Item reduction processes yielded a 13-item version (SEPI-13); in analysis of this version, the original factor structure was maintained. Lower scores on Confidence-challenge were significantly associated with disability (p = 0.002), depression (p = 0.001) and fatigue (p = 0.001). Self-reported barriers to exercise were particularly prevalent in those experiencing fatigue and anxiety. Conclusions The SEPI-13 is a brief instrument that allows assessment of exercise preferences and barriers in the stroke population. This new tool can be employed by health professionals to inform the development of individually tailored exercise interventions.

The analysis of open-minded attitudes towards sexuality in general requires a construct based on attitudinal dimensions. Although several existing studies involve sexual attitudes, they differ substantially and standardized conceptual work is missing. Thus, the authors introduce the latent variable sexual openness to develop a construct based on self-oriented attitudes towards different sexual topics. Available survey data of female German students in a steady relationship allowed providing a first empirical test for the applicability of this construct. Five subdimensions are acknowledged central for sexual openness: sexual practices, masturbation, bisexuality, permissiveness, and pornography consumption. Confirmatory factor analysis and correlations confirmed the idea of an underlying mechanism with an impact on all five variables. Though further validation of the construct of sexual openness is required, the findings strongly support the notion of an overarching latent attitude variable, which influences the individual relation to everything sexual. The results were compared to other studies and potential approaches for future analyses were proposed.

Decisions are often based on imprecise, uncertain or vague information. Likewise, the consequences of an action are often equally unpredictable, thus putting the decision maker into a twofold jeopardy. Assuming that the effects of an action can be modeled by a random variable, then the decision problem boils down to comparing different effects (random variables) by comparing their distribution functions. Although the full space of probability distributions cannot be ordered, a properly restricted subset of distributions can be totally ordered in a practically meaningful way. We call these loss-distributions, since they provide a substitute for the concept of loss-functions in decision theory. This article introduces the theory behind the necessary restrictions and the hereby constructible total ordering on random loss variables, which enables decisions under uncertainty of consequences. Using data obtained from simulations, we demonstrate the practical applicability of our approach., Comment: preprint of a correction to the article with the same name, published with PLOS ONE, and currently under review

BACKGROUND: The characteristics of Emergency Department (ED) attendances due to mental or behavioural health disorders need to be described to enable appropriate development of services. We aimed to describe the epidemiology of mental health-related ED attendances within health care systems free at the point of access, including clinical reason for presentation, previous service use, and patient sociodemographic characteristics. METHOD: Systematic review and meta-analysis of observational studies describing ED attendances by patients with common mental health conditions. FINDINGS: 18 studies from seven countries met eligibility criteria. Patients attending due to mental or behavioural health disorders accounted for 4% of ED attendances; a third were due to self-harm or suicidal ideation. 58.1% of attendees had a history of psychiatric illness and up to 58% were admitted. The majority of studies were single site and of low quality so results must be interpreted cautiously. CONCLUSIONS: Prevalence studies of mental health-related ED attendances are required to enable the development of services to meet specific needs.

Ecological research suggests increased diversity may improve ecosystem services, as well as yield stability; however, such theories are sometimes disproven by agronomic research, particularly at higher diversity levels. We conducted a meta-analysis on 2,753 studies in 48 articles published over the last 53 years to test: if biological N2 fixation (BNF) supplies adequate nitrogen (N) for plant growth relative to synthetic fertilizers; how crop physiological traits affect legume-grass symbiosis; and, how cultural practices affect BNF over a range of soils and climates overtime (in polycultures versus sole grasslands). Globally, net primary productivity (NPP; total aboveground production response of grass and legume in higher-diversity treatments) increased 44% via legume associations relative to sole grass controls (including both with and without N fertilizer). Several moderating variables affected NPP including: (i) plant photosynthetic pathway (mixtures of C3 grasses resulted in a 57% increase in NPP, whereas mixtures of C4 grasses resulted in a 31% increase; similarly cool-season legumes increased NPP 52% compared to a 27% increase for warm-season legumes relative to grasslands without diversity); (ii) legume life cycle [NPP response for perennial legume mixtures was 50% greater than sole grass controls, followed by a 28% increase for biennial, and a 0% increase for annual legumes)]; and, (iii) species richness (one leguminous species in a grassland agroecosystem resulted in 52% increase in NPP, whereas >2 legumes resulted in only 6% increases). Temporal and spatial effect sizes also influenced facilitation, considering facilitation was greatest (114% change) in Mediterranean climates followed by oceanic (84%), and tropical savanna (65%) environments; conversely, semiarid and subarctic systems had lowest Rhizobium-induced changes (5 and 0% change, respectively). Facilitation of grass production by legumes was also affected by soil texture. For example, a 122% NPP increase was observed in silt clay soils compared to 14% for silt loam soils. Niche complementarity effects were greatest prior to 1971 (61% change), compared to recent studies (2011-2016; -7% change), likely owing to reduced global sulfur deposition and increased ambient temperatures overtime. These historical trends suggest potential for legume intercrops to displace inorganic-N fertilizer and sustainably intensify global NPP. Results herein provide a framework for ecologists and agronomists to improve crop diversification systems, refine research goals, and heighten BNF capacities in agro-grasslands.

Background Erectile dysfunction (ED) is common among men on opioid replacement therapy (ORT), but most previous studies exploring its prevalence and determinants yielded contrasting findings. Moreover, the impact of ED on patients’ quality of life (QoL) has been seldom explored. Objective To explore the prevalence and determinants of ED in men on ORT, and the impact on QoL. Methods In a multicentre cross-sectional study, we recruited 797 consecutive male patients on methadone and buprenorphine treatment, collected data on demographic, clinical, and psychopathological factors, and explored their role as predictors of ED and QoL through univariate and multivariate analysis. ED severity was assessed with a self-assessment questionnaire. Results Nearly half of patients in our sample were sexually inactive or reported some degree of ED. Some demographic, clinical and psychopathological variables significantly differed according to the presence or absence of ED. Multivariate regression analysis indicated that age, employment, smoke, psychoactive drugs, opioid maintenance dosage, and severity of psychopathological factors significantly influenced the risk and severity of ED. QoL was worse in patients with ED and significantly correlated with ED severity. Age, education, employment, opioid maintenance dosage, ED score, and severity of psychopathology significantly influenced QoL in the multivariate analysis. Conclusions ED complaints can be explored in male opioid users on ORT through a simple and quick self-assessment tool. ED may have important effects on emotional and social well-being, and may affect outcome.

Human movements are prone to errors that arise from inaccuracies in both our perceptual processing and execution of motor commands. We can reduce such errors by both improving our estimates of the state of the world and through online error correction of the ongoing action. Two prominent frameworks that explain how humans solve these problems are Bayesian estimation and stochastic optimal feedback control. Here we examine the interaction between estimation and control by asking if uncertainty in estimates affects how subjects correct for errors that may arise during the movement. Unbeknownst to participants, we randomly shifted the visual feedback of their finger position as they reached to indicate the center of mass of an object. Even though participants were given ample time to compensate for this perturbation, they only fully corrected for the induced error on trials with low uncertainty about center of mass, with correction only partial in trials involving more uncertainty. The analysis of subjects’ scores revealed that participants corrected for errors just enough to avoid significant decrease in their overall scores, in agreement with the minimal intervention principle of optimal feedback control. We explain this behavior with a term in the loss function that accounts for the additional effort of adjusting one’s response. By suggesting that subjects’ decision uncertainty, as reflected in their posterior distribution, is a major factor in determining how their sensorimotor system responds to error, our findings support theoretical models in which the decision making and control processes are fully integrated.Figures

This study examines the association between childhood socioeconomic position and objective physical capability including new functional measures of potential relevance to a population in late-middle age. The study population covers two Danish birth cohorts followed-up in the Copenhagen Aging and Midlife Biobank (age 48–58 years, 2009–2011, N = 4,204). Results from linear regression models revealed that being born in higher socioeconomic position was associated with higher jump height: Paternal occupational class four = 0.19 cm (95% confidence interval (CI): -0.44, 0.82), three = 0.59 cm (95% CI: -0.02, 1.19), two = 1.29 cm (95% CI: 0.64, 1.94), and one = 1.29 cm (95% CI: 0.45, 2.13) (reference = five); medium parental social class = 0.88 cm (95% CI: 0.03, 1.72) and high = 1.79 cm (95% CI: 0.94, 2.63) (reference = low). Higher childhood socioeconomic position was also associated with better chair rise performance and hand grip strength, while among women it was related to reduced flexibility: Medium parental social class = -1.31 cm (95% CI: -3.05, 0.42) and high = -2.20 cm (95% CI: -3.94, -0.47) (reference = low); unwed mother = 1.75 cm (95% CI: 0.36, 3.14) (reference = married). Overall, the findings suggest that higher childhood socioeconomic position is primarily related to moderately better scores in the most strenuous physical capability measures and hand grip strength among healthy adults in late-middle age.

Recent studies on machine learning technology have reported successful performances in some visual and auditory recognition tasks, while little has been reported in the field of olfaction. In this paper we report computational methods to predict the odor impression of a chemical from its physicochemical properties. Our predictive model utilizes nonlinear dimensionality reduction on mass spectra data and performs the clustering of descriptors by natural language processing. Sensory evaluation is widely used to measure human impressions to smell or taste by using verbal descriptors, such as "spicy" and "sweet". However, as it requires significant amounts of time and human resources, a large-scale sensory evaluation test is difficult to perform. Our model successfully predicts a group of descriptors for a target chemical through a series of computer simulations. Although the training text data used in the language modeling is not specialized for olfaction, the experimental results show that our method is useful for analyzing sensory datasets. This is the first report to combine machine olfaction with natural language processing for odor character prediction.

Neuroscience investigations are most often focused on the prediction of future perception or decisions based on prior brain states or stimulus presentations. However, the brain can also process information retroactively, such that later stimuli impact conscious percepts of the stimuli that have already occurred (called “postdiction”). Postdictive effects have thus far been mostly unimodal (such as apparent motion), and the models for postdiction have accordingly been limited to early sensory regions of one modality. We have discovered two related multimodal illusions in which audition instigates postdictive changes in visual perception. In the first illusion (called the “Illusory Audiovisual Rabbit”), the location of an illusory flash is influenced by an auditory beep-flash pair that follows the perceived illusory flash. In the second illusion (called the “Invisible Audiovisual Rabbit”), a beep-flash pair following a real flash suppresses the perception of the earlier flash. Thus, we showed experimentally that these two effects are influenced significantly by postdiction. The audiovisual rabbit illusions indicate that postdiction can bridge the senses, uncovering a relatively-neglected yet critical type of neural processing underlying perceptual awareness. Furthermore, these two new illusions broaden the Double Flash Illusion, in which a single real flash is doubled by two sounds. Whereas the double flash indicated that audition can create an illusory flash, these rabbit illusions expand audition’s influence on vision to the suppression of a real flash and the relocation of an illusory flash. These new additions to auditory-visual interactions indicate a spatio-temporally fine-tuned coupling of the senses to generate perception.

Background Nursing notes have not been widely used in prediction models for clinical outcomes, despite containing rich information. Advances in natural language processing have made it possible to extract information from large scale unstructured data like nursing notes. This study extracted the sentiment—impressions and attitudes—of nurses, and examined how sentiment relates to 30-day mortality and survival. Methods This study applied a sentiment analysis algorithm to nursing notes extracted from MIMIC-III, a public intensive care unit (ICU) database. A multiple logistic regression model was fitted to the data to correlate measured sentiment with 30-day mortality while controlling for gender, type of ICU, and SAPS-II score. The association between measured sentiment and 30-day mortality was further examined in assessing the predictive performance of sentiment score as a feature in a classifier, and in a survival analysis for different levels of measured sentiment. Results Nursing notes from 27,477 ICU patients, with an overall 30-day mortality of 11.02%, were extracted. In the presence of known predictors of 30-day mortality, mean sentiment polarity was a highly significant predictor in a multiple logistic regression model (Adjusted OR = 0.4626, p < 0.001, 95% CI: [0.4244, 0.5041]) and led to improved predictive accuracy (AUROC = 0.8189 versus 0.8092, 95% BCI of difference: [0.0070, 0.0126]). The Kaplan Meier survival curves showed that mean sentiment polarity quartiles are positively correlated with patient survival (log-rank test: p < 0.001). Conclusions This study showed that quantitative measures of unstructured clinical notes, such as sentiment of clinicians, correlate with 30-day mortality and survival, thus can also serve as a predictor of patient outcomes in the ICU. Therefore, further research is warranted to study and make use of the wealth of data that clinical notes have to offer.

Background: Though many overweight and obese adults attempt to lose weight without formal support, little is known about the strategies used in self-directed weight loss attempts. We set out to assess cognitive and behavioural strategies for weight loss and their associations with weight change. Methods: Prospective, web-based cohort study of overweight UK adults (BMI≥25kg/m2) trying to lose weight through behaviour change. Strategy use was assessed using the OxFAB questionnaire and evaluated (1) at the domain level, (2) through exploratory factor analysis, and (3) in a model of strategies deemed a priori to be “essential” to weight management. Associations with weight change at 3 months were tested using linear regression. Results: 486 participants answered all questions; 194 reported weight at baseline and at 3 months (mean weight change -3.3kg (SD 4.1)). Greater weight loss was significantly associated with the motivational support domain (-2.4kg, 95% CI -4.4 to -0.4), dietary impulse control (from factor analysis) (-0.6kg, 95% CI -1.1 to -0.03), and weight loss planning and monitoring (from factor analysis) (-1.3kg, 95% CI -2.0 to -0.5). Higher scores in the model of essential behavioural strategies were significantly associated with greater weight loss (compared to participants using 6 or fewer of the 9 strategies, using 7 or more of the 9 strategies was associated with a 2.13kg greater weight loss (SE 0.58, p Conclusions: Despite heterogeneity in the strategies employed for weight loss, coherent patterns of behaviours emerged for individual participants, some of which were associated with greater weight loss, including strategies relating to dietary impulse control, weight loss planning and monitoring, motivational support, information seeking and self-monitoring. Trials could test the effect of promoting use of these patterns on weight loss.

For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. We performed expression quantitative trait loci (eQTL) mapping in each population and show genetic correlation of gene expression depends on shared ancestry proportions. Using elastic net modeling with cross validation to optimize genotypic predictors of gene expression in each population, we show the genetic architecture of gene expression for most predictable genes is sparse. We found the best predicted gene in each population, TACSTD2 in AFA and CHURC1 in CAU and HIS, had similar prediction performance across populations with R2 > 0.8 in each population. However, we identified a subset of genes that are well-predicted in one population, but poorly predicted in another. We show these differences in predictive performance are due to allele frequency differences between populations. Using genotype weights trained in MESA to predict gene expression in independent populations showed that a training set with ancestry similar to the test set is better at predicting gene expression in test populations, demonstrating an urgent need for diverse population sampling in genomics. Our predictive models and performance statistics in diverse cohorts are made publicly available for use in transcriptome mapping methods at https://github.com/WheelerLab/DivPop., Author summary Most genome-wide association studies (GWAS) have been conducted in populations of European ancestry leading to a disparity in understanding the genetics of complex traits between populations. For many complex traits, gene regulation is critical, given the consistent enrichment of regulatory variants among trait-associated variants. However, it is still unknown how the effects of these key variants differ across populations. We used data from MESA to study the underlying genetic architecture of gene expression by optimizing gene expression prediction within and across diverse populations. The populations with genotype and gene expression data available are from individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. After calculating the prediction performance, we found that many genes that were well predicted in one population are poorly predicted in another. We further show that a training set with ancestry similar to the test set resulted in better gene expression predictions, demonstrating the need to incorporate diverse populations in genomic studies. Our gene expression prediction models and performance statistics are publicly available to facilitate future transcriptome mapping studies in diverse populations.

Purpose: Measuring accurate thresholds in children can be challenging. A typical psychophysical experiment is usually too long to keep children engaged. However, a reduction in the number of trials decreases the precision of the threshold estimate. We evaluated the efficiency of forced-choice paradigms with 2 or 4 alternatives (2-AFC, 4-AFC) in a disparity detection experiment. 4-AFC paradigms are statistically more efficient, but also more cognitively demanding, which might offset their theoretical advantage in young children. Methods: We ran simulations evaluating bias and precision of threshold estimates of 2-AFC and 4-AFC paradigms. In addition, we measured disparity thresholds in 43 children (aged 6 to 17 years) with a 4-AFC paradigm and in 49 children (aged 4 to 17 years) with a 2-AFC paradigm, both using an adaptive weighted one-up one-down staircase. Results: Simulations indicated a similar bias and precision for a 2-AFC paradigm with double the number of trials as a 4-AFC paradigm. On average, estimated threshold of the simulated data was equal to the model threshold, indicating no bias. The precision was improved with an increasing number of trials. Likewise, our data showed a similar bias and precision for a 2-AFC paradigm with 60 trials as for a 4-AFC paradigm with 30 trials. Trials in the 4-AFC paradigm took slightly longer as participants scanned more alternatives. However, the 4-AFC task still ended up faster for a given precision. Conclusion: Bias and precision were similar in a 4-AFC task compared to a 2-AFC task with double the number of trials. However, a 4-AFC paradigm was more time efficient and is therefore recommended.

Background Deep learning (DL) based solutions have been proposed for interpretation of several imaging modalities including radiography, CT, and MR. For chest radiographs, DL algorithms have found success in the evaluation of abnormalities such as lung nodules, pulmonary tuberculosis, cystic fibrosis, pneumoconiosis, and location of peripherally inserted central catheters. Chest radiography represents the most commonly performed radiological test for a multitude of non-emergent and emergent clinical indications. This study aims to assess accuracy of deep learning (DL) algorithm for detection of abnormalities on routine frontal chest radiographs (CXR), and assessment of stability or change in findings over serial radiographs. Methods and findings We processed 874 de-identified frontal CXR from 724 adult patients (> 18 years) with DL (Qure AI). Scores and prediction statistics from DL were generated and recorded for the presence of pulmonary opacities, pleural effusions, hilar prominence, and enlarged cardiac silhouette. To establish a standard of reference (SOR), two thoracic radiologists assessed all CXR for these abnormalities. Four other radiologists (test radiologists), unaware of SOR and DL findings, independently assessed the presence of radiographic abnormalities. A total 724 radiographs were assessed for detection of findings. A subset of 150 radiographs with follow up examinations was used to asses change over time. Data were analyzed with receiver operating characteristics analyses and post-hoc power analysis. Results About 42% (305/ 724) CXR had no findings according to SOR; single and multiple abnormalities were seen in 23% (168/724) and 35% (251/724) of CXR. There was no statistical difference between DL and SOR for all abnormalities (p = 0.2–0.8). The area under the curve (AUC) for DL and test radiologists ranged between 0.837–0.929 and 0.693–0.923, respectively. DL had lowest AUC (0.758) for assessing changes in pulmonary opacities over follow up CXR. Presence of chest wall implanted devices negatively affected the accuracy of DL algorithm for evaluation of pulmonary and hilar abnormalities. Conclusions DL algorithm can aid in interpretation of CXR findings and their stability over follow up CXR. However, in its present version, it is unlikely to replace radiologists due to its limited specificity for categorizing specific findings.

Street imagery is a promising big data source providing current and historical images in more than 100 countries. Previous studies used this data to audit built environment features. Here we explore a novel application, using Google Street View (GSV) to predict travel patterns at the city level. We sampled 34 cities in Great Britain. In each city, we accessed GSV images from 1000 random locations from years overlapping with the 2011 Census and the 2011-2013 Active People Survey (APS). We manually annotated images into seven categories of road users. We developed regression models with the counts of images of road users as predictors. Outcomes included Census-reported commute shares of four modes (walking plus public transport, cycling, motorcycle, and car), and APS-reported past-month participation in walking and cycling. In bivariate analyses, we found high correlations between GSV counts of cyclists (GSV-cyclists) and cycle commute mode share (r=0.92) and past-month cycling (r=0.90). Likewise, GSV-pedestrians was moderately correlated with past-month walking for transport (r=0.46), GSV-motorcycles was moderately correlated with commute share of motorcycles (r=0.44), and GSV-buses was highly correlated with commute share of walking plus public transport (r=0.81). GSV-car was not correlated with car commute mode share (r=-0.12). However, in multivariable regression models, all mode shares were predicted well. Cross-validation analyses showed good prediction performance for all the outcomes except past-month walking. Street imagery is a promising new big data source to predict urban mobility patterns. Further testing across multiple settings is warranted both for cross-sectional and longitudinal assessments., Comment: Paper submitted for peer review. 7 figures. 3 Tables

Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis., Author Summary Different models of the same process represent distinct hypotheses about reality. These can be decided between within the framework of model selection, where the evidence for each is given by their ability to reproduce a set of experimental data. Even if one of the models is correct, the chances of identifying it can be hindered by the quality of the data, both in terms of its signal to measurement error ratio and the intrinsic discriminatory potential of the experiment undertaken. This potential can be predicted in various ways, and maximising it is one aim of experimental design. In this work we present a computationally efficient method of experimental design for model selection. We exploit the efficiency to consider the implications of the realistic case where all models are more or less incorrect, showing that experiments can be chosen that, considered individually, lead to unequivocal support for opposed hypotheses.

The aim of this experiment was to study the growth-promoting and adverse impact of athlete leaders’ competence–supportive and –thwarting behavior on the motivation and performance of team members. Male soccer players (N = 144; MAge = 14.2) were allocated to ad-hoc teams of five soccer players. These teams participated in two sessions, being randomly exposed to an athlete leader who acted either competence-supportive, competence-thwarting, or neutral during the second session. When the athlete leader was competence-supportive (versus competence-thwarting), his teammates’ intrinsic motivation and performance increased (versus decreased) compared with the control condition. The leader’s impact on intrinsic motivation was fully accounted for by team members’ competence satisfaction. These findings recommend coaches to invest in the competence-supportive power of their athlete leaders to establish an optimally motivating and performance-enhancing team environment. ispartof: PLoS One vol:13 issue:7 pages:e0200480-e0200480 ispartof: location:United States status: published

Background Peak oxygen uptake (VO2peak) in Paralympic sitting sports athletes represents their maximal ability to deliver energy aerobically in an upper-body mode, with values being influenced by sex, disability-related physiological limitations, sport-specific demands, training status and how they are tested. Objectives To identify VO2peak values in Paralympic sitting sports, examine between-sports differences and within-sports variations in VO2peak and determine the influence of sex, age, body-mass, disability and test-mode on VO2peak. Design Systematic literature review and meta-analysis. Data sources PubMed, CINAHL, SPORTDiscusTM and EMBASE were systematically searched in October 2016 using relevant medical subject headings, keywords and a Boolean. Eligibility criteria Studies that assessed VO2peak values in sitting sports athletes with a disability in a laboratory setting were included. Data synthesis Data was extracted and pooled in the different sports disciplines, weighted by the Dersimonian and Laird random effects approach. Quality of the included studies was assessed with a modified version of the Downs and Black checklist by two independent reviewers. Meta-regression and pooled-data multiple regression analyses were performed to assess the influence of sex, age, body-mass, disability, test mode and study quality on VO2peak. Results Of 6542 retrieved articles, 57 studies reporting VO2peak values in 14 different sitting sports were included in this review. VO2peak values from 771 athletes were used in the data analysis, of which 30% participated in wheelchair basketball, 27% in wheelchair racing, 15% in wheelchair rugby and the remaining 28% in the 11 other disciplines. Fifty-six percent of the athletes had a spinal cord injury and 87% were men. Sports-discipline-averaged VO2peak values ranged from 2.9 L∙min-1 and 45.6 mL∙kg-1∙min-1 in Nordic sit skiing to 1.4 L∙min-1 and 17.3 mL∙kg-1∙min-1 in shooting and 1.3 L∙min-1 and 18.9 mL∙kg-1∙min-1 in wheelchair rugby. Large within-sports variation was found in sports with few included studies and corresponding low sample sizes. The meta-regression and pooled-data multiple regression analyses showed that being a man, having an amputation, not being tetraplegic, testing in a wheelchair ergometer and treadmill mode, were found to be favorable for high absolute and body-mass normalized VO2peak values. Furthermore, high body mass was favourable for high absolute VO2peak values and low body mass for high body-mass normalized VO2peak values. Conclusion The highest VO2peak values were found in Nordic sit skiing, an endurance sport with continuously high physical efforts, and the lowest values in shooting, a sport with low levels of displacement, and in wheelchair rugby where mainly athletes with tetraplegia compete. However, VO2peak values need to be interpreted carefully in sports-disciplines with few included studies and large within-sports variation. Future studies should include detailed information on training status, sex, age, test mode, as well as the type and extent of disability in order to more precisely evaluate the effect of these factors on VO2peak.

Background Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets. Methods and Findings We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3–6 months and 1–2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (n = 3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3–6 months (MD 0.74 kg, 95%CI −1.49 to 0.01 kg; I2 = 53%; n = 1745, 14 trials; moderate quality evidence) and 1–2 years (MD 0.48 kg, 95%CI −1.44 kg to 0.49 kg; I2 = 12%; n = 1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3–6 months and 1–2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern. Conclusions Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.

Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.

Aim Since cardiovascular magnetic resonance feature-tracking (CMR-FT) has been demonstrated to be of incremental clinical merit we investigated the interchangeability of global left and right ventricular strain parameters between different CMR-FT software solutions. Material and methods CMR-cine images of 10 patients without significant reduction in LVEF and RVEF and 10 patients with a significantly impaired systolic function were analyzed using two different types of FT-software (TomTec, Germany; QStrain, Netherlands). Global longitudinal strains (LV GLS, RV GLS), global left ventricular circumferential (GCS) and radial strains (GRS) were assessed. Differences in intra- and inter-observer variability within and between software types based on single and up to three repeated and subsequently averaged measurements were evaluated. Results Inter-vendor agreement was highest for GCS followed by LV GLS. GRS and RV GLS showed lower inter-vendor agreement. Variability was consistently higher in healthy volunteers as compared to the patient group. Intra-vendor reproducibility was excellent for GCS, LV GLS and RV GLS, but lower for GRS. The impact of repeated measurements was most pronounced for GRS and RV GLS on an intra-vendor level. Conclusion Cardiac pathology has no influence on CMR-FT reproducibility. LV GLS and GCS qualify as the most robust parameters within and between individual software types. Since both parameters can be interchangeably assessed with different software solutions they may enter the clinical arena for optimized diagnostic and prognostic evaluation of cardiovascular morbidity and mortality in various pathologies.

To cause disease, Clostridioides (Clostridium) difficile must resist killing by innate immune effectors in the intestine, including the host antimicrobial peptide, cathelicidin (LL-37). The mechanisms that enable C. difficile to adapt to the intestine in the presence of antimicrobial peptides are unknown. Expression analyses revealed an operon, CD630_16170-CD630_16190 (clnRAB), which is highly induced by LL-37 and is not expressed in response to other cell-surface active antimicrobials. This operon encodes a predicted transcriptional regulator (ClnR) and an ABC transporter system (ClnAB), all of which are required for function. Analyses of a clnR mutant indicate that ClnR is a pleiotropic regulator that directly binds to LL-37 and controls expression of numerous genes, including many involved in metabolism, cellular transport, signaling, gene regulation, and pathogenesis. The data suggest that ClnRAB is a novel regulatory mechanism that senses LL-37 as a host signal and regulates gene expression to adapt to the host intestinal environment during infection., Author summary C. difficile is a major nosocomial pathogen that causes severe diarrheal disease. Though C. difficile is known to inhabit the human gastrointestinal tract, the mechanisms that allow this pathogen to adapt to the intestine and survive host defenses are not known. In this work, we investigated the response of C. difficile to the host defense peptide, LL-37, to determine the mechanisms underlying host adaptation and survival. Expression analyses revealed a previously unknown locus, which we named clnRAB, that is highly induced by LL-37 and acts as a global regulator of gene expression in C. difficile. Mutant analyses indicate that ClnRAB is a novel regulatory system that senses LL-37 as a host signal to regulate adaptation to the intestinal environment.

BACKGROUND: Parents who lose a child by suicide have elevated risks of depression. No clinical prediction tools exist to identify which suicide-bereaved parents will be particularly vulnerable; we aimed to create a prediction model for long-term depression for this purpose. METHOD: During 2009 and 2010 we collected data using a nationwide study-specific questionnaire among parents in Sweden who had lost a child aged 15-30 by suicide in years 2004-2007. Current depression was assessed with the Patient Health Questionnaire (PHQ-9) and a single question on antidepressant use. We considered 26 potential predictors assumed clinically assessable at the time of loss, including socio-economics, relationship status, history of psychological stress and morbidity, and suicide-related circumstances. We developed a novel prediction model using logistic regression with all subsets selection and stratified cross-validation. The model was assessed for classification performance and calibration, overall and stratified by time since loss. RESULTS: In total 666/915 (73%) participated. The model showed acceptable classification performance (adjusted area under the curve [AUC] = 0.720, 95% confidence interval [CI] 0.673-0.766), but performed classification best for those at shortest time since loss. Agreement between model-predicted and observed risks was fair, but with a tendency for underestimation and overestimation for individuals with shortest and longest time since loss, respectively. The identified predictors include female sex (odds ratio [OR] = 1.84); sick-leave (OR = 2.81) or unemployment (OR = 1.64); psychological premorbidity debuting during the last 10 years, before loss (OR = 3.64), or more than 10 years ago (OR = 4.96); suicide in biological relatives (OR = 1.54); with non-legal guardianship during the child's upbringing (OR = 0.48); and non-biological parenthood (OR = 0.22) found as protective. CONCLUSIONS: Our prediction model shows promising internal validity, but should be externally validated before application. Psychological premorbidity seems to be a prominent predictor of long-term depression among suicide-bereaved parents, and thus important for healthcare providers to assess.

Traffic surveillance systems are interesting to many researchers to improve the traffic control and reduce the risk caused by accidents. In this area, many published works are only concerned about vehicle detection in normal conditions. The camera may vibrate due to wind or bridge movement. Detection and tracking of vehicles is a very difficult task when we have bad weather conditions in winter (snowy, rainy, windy, etc.), dusty weather in arid and semi-arid regions, at night, etc. Also, it is very important to consider speed of vehicles in the complicated weather condition. In this paper, we improved our method to track and count vehicles in dusty weather with vibrating camera. For this purpose, we used a background subtraction based strategy mixed with an extra processing to segment vehicles. In this paper, the extra processing included the analysis of the headlight size, location, and area. In our work, tracking was done between consecutive frames via a generalized particle filter to detect the vehicle and pair the headlights using the connected component analysis. So, vehicle counting was performed based on the pairing result, with Centroid of each blob we calculated distance between two frames by simple formula and hence dividing it by the time between two frames obtained from the video. Our proposed method was tested on several video surveillance records in different conditions such as dusty or foggy weather, vibrating camera, and in roads with medium-level traffic volumes. The results showed that the new proposed method performed better than our previously published method and other methods, including the Kalman filter or Gaussian model, in different traffic conditions.

Objective This study aimed to assess predictive ability of heart rate variability (HRV) for pregnancy outcomes with in vitro fertilization (IVF) treatment. Research design and method A total of 180 women with 261 cycles of IVF and 211 embryo transfers (ETs) were analyzed. HRV was measured at four times during IVF treatment: the first date of menstruation, r-HCG (Ovidrel) administration, and before and after ET. Pregnancy indicators included chemical pregnancy, ongoing pregnancy (> 10 weeks), and live birth (pregnancy > 24 weeks). Mixed effect models were applied to identify predictors for IVF pregnancy. The area under the receiver operating characteristic curve (AUC) was used to assess prediction models for pregnancy. Results The HRV values increased during IVF treatment and then decreased after ET. The trend of changes in HRV values during IVF treatment was significant among patients with chemical pregnancy (p < 0.01) and those with live birth (p = 0.02). Women without pregnancy had lower HRV compared to those with IVF pregnancy (p < 0.05). With a one unit increase in HRV difference before and after ET, the odds of chemical pregnancy decreased by 18% (odds ratio; OR: 0.82, 95% CI: 0.70–0.97, p < 0.02). With a one year increase in maternal age, the odds decreased by 16% (OR: 0.84, 95% CI: 0.76–0.93, p < 0.01), 25% (OR: 0.75, 95% CI: 0.58–0.93, p = 0.02), and 28% (OR: 0.72, 95% CI: 0.54–0.91, p = 0.01) for chemical pregnancy, ongoing pregnancy, and live birth, respectively. The AUCs were 0.77 (95% CI: 0.70, 0.84), 0.89 (0.79, 0.98), and 0.91(0.83, 0.99) for the prediction models for chemical pregnancy, ongoing pregnancy, and live birth, respectively. Conclusions Reduced HRV may be an indicator for low chance of IVF pregnancy. The changes in HRV before and after ET and maternal age might be prognostic predictors of IVF pregnancy.

Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set.

The Journal of Physiology and British Journal of Pharmacology jointly published an editorial series in 2011 to improve standards in statistical reporting and data analysis. It is not known whether reporting practices changed in response to the editorial advice. We conducted a cross-sectional analysis of reporting practices in a random sample of research papers published in these journals before (n = 202) and after (n = 199) publication of the editorial advice. Descriptive data are presented. There was no evidence that reporting practices improved following publication of the editorial advice. Overall, 76-84% of papers with written measures that summarized data variability used standard errors of the mean, and 90-96% of papers did not report exact p-values for primary analyses and post-hoc tests. 76-84% of papers that plotted measures to summarize data variability used standard errors of the mean, and only 2-4% of papers plotted raw data used to calculate variability. Of papers that reported p-values between 0.05 and 0.1, 56-63% interpreted these as trends or statistically significant. Implied or gross spin was noted incidentally in papers before (n = 10) and after (n = 9) the editorial advice was published. Overall, poor statistical reporting, inadequate data presentation and spin were present before and after the editorial advice was published. While the scientific community continues to implement strategies for improving reporting practices, our results indicate stronger incentives or enforcements are needed.

The melting temperature (Tm) of a protein is the temperature at which half of the protein population is in a folded state. Therefore, Tm is a measure of the thermostability of a protein. Increasing the Tm of a protein is a critical goal in biotechnology and biomedicine. However, predicting the change in melting temperature (dTm) due to mutations at a single residue is difficult because it depends on an intricate balance of forces. Existing methods for predicting dTm have had similar levels of success using generally complex models. We find that training a machine learning model with a simple set of easy to calculate physicochemical descriptors describing the local environment of the mutation performed as well as more complicated machine learning models and is 2-6 orders of magnitude faster. Importantly, unlike in most previous publications, we perform a blind prospective test on our simple model by designing 96 variants of a protein not in the training set. Results from retrospective and prospective predictions reveal the limited applicability domain of each model. This study highlights the current deficiencies in the available dTm dataset and is a call to the community to systematically design a larger and more diverse experimental dataset of mutants to prospectively predict dTm with greater certainty.

Biomarkers are widely used to confirm the presence of infection. However, it would be of the greatest importance to predict in advance the occurrence or worsening of organ dysfunction in infected patients allowing timely antibiotic escalation. This study investigates the ability of procalcitonin (PCT) and MR-proADM to predict the transition to sepsis in infected patients. The study was conducted in a neurointensive care unit over a three-month period. We included both patients with and without infection to investigate the specificity of organ dysfunction prediction in infected patients. Daily measurement of PCT and MR-proADM, SOFA, Pitt, and CPIS were performed. To measure the correlation between each biomarker and each severity score, linear mixed-effects models were developed. For each biomarker-score combination we tested the correlation of the score with the biomarker measured one and two days before, the same day, and the day after. Sixty-four critically ill patients, 31 with infection, were enrolled. The statistically significant biomarker-score combinations were PCT-SOFA, MR-proADM-SOFA, MR-proADM-Pitt, and MR-proADM-CPIS. The MR-proADM models predicting Pitt and CPIS variations with 24-hour anticipation showed the best fit. The scores increased by 0.6 ± 0.3 and 0.4 ± 0.2 for each unitary biomarker increase, respectively. The MR-proADM-SOFA combinations were equivalent when the biomarker was measured the day before or the same day (score increases were 1.5 ± 0.4 and 1.9 ± 0.4, respectively). The PCT-SOFA model had the best fit when PCT was measured the same day of the score. There was no difference in the predictive ability of the biomarker in infected and non-infected patients. This was a pivotal study conducted in a single neurointensive centre on a limited number of patients, and as such it does not provide definitive conclusions. PR-proADM predicted occurrence and worsening of organ failure in critically ill patients with and without infection. The combination with infection diagnostic biomarkers such as PCT would allow predicting evolution to sepsis in infected patients.

Purpose The aim of this study was to evaluate the diagnostic performance of choline positron emission tomography/computed tomography (PET/CT) for the detection of bone metastasis in patients with prostate cancer. Methods MEDLINE, EMBASE and the Cochrane Library were searched up to 20 February 2018 for studies that used 11C-choline or 18F-choline PET/CT for the detection of bone metastasis in patients with prostate cancer and “histopathology and/or clinical follow-up” as the reference standard. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled diagnostic accuracy with the 95% confidence interval (CI) was calculated using a bivariate random effects model. We also constructed hierarchical summary receiver operating characteristic curves and performed meta-regression analyses. Results Fourteen studies with reasonable methodological quality were included in the analysis. On a per-patient basis, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.89 (95% CI 0.80–0.94), 0.98 (95% CI 0.95–0.99), 40.4 (95% CI 19.7–82.6), 0.12 (95% CI 0.07–0.20), and 344 (95% CI 148–803), respectively. On a per-lesion basis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.91 (95% CI 0.85–0.94), 0.97 (95% CI 0.95–0.98), 34.1 (95% CI 20.0–58.1), 0.10 (95% CI 0.06–0.16), and 358 (95% CI 165–778), respectively. In the meta-regression analysis, the clinical setting (staging vs. restaging) was the only source of study heterogeneity on a per-patient basis. Conclusions Choline PET/CT shows excellent diagnostic performance for the detection of bone metastasis. However, a negative choline PET/CT result cannot ensure the lack of bone metastasis.

This paper considers the DCSK system under jamming environment. We consider both fast and slow switching pulse jamming (PJ). We derive approximations of the system bit error rates (BERs) in analytic expressions containing only well-known special functions, from which we show that for both jamming cases increasing the spreading factor can enhance the BER. In addition, we reveal that under the fast switching PJ, the BER does not depend on the jamming duty cycle ρ when ρ ≤ 0.5, however when ρ > 0.5, increasing its value degrades the BER. Moreover, we find out that under the slow switching PJ, increasing ρ may either enhance or degrade the BER.

Previous work suggests that to restore postural stability for individuals with lower-limb amputation, ankle-foot prostheses should be designed with a flat effective rocker shape for standing. However, most commercially available ankle-foot prostheses are designed with a curved effective rocker shape for walking. To address the demands of both standing and walking, we designed a novel bimodal ankle-foot prosthesis that can accommodate both functional modes using a rigid foot plate and an ankle that can lock and unlock. The primary objective of this study was to determine if the bimodal ankle-foot system could improve various aspects of standing balance (static, dynamic, and functional) and mobility in a group of Veterans with lower-limb amputation (n = 18). Standing balance was assessed while subjects completed a series of tests on a NeuroCom Clinical Research System (NeuroCom, a Division of Natus, Clackamas, OR), including a Sensory Organization Test, a Limits of Stability Test, and a modified Motor Control Test. Few statistically significant differences were observed between the locked and unlocked ankle conditions while subjects completed these tests. However, in the absence of visual feedback, the locked bimodal ankle appeared to improve static balance in a group of experienced lower-limb prosthesis users whose PLUS-M mobility rating was higher than approximately 73% of the sample population used to develop the PLUS-M survey. Given the statistically significant increase in mean equilibrium scores between the unlocked and locked conditions (p = 0.004), future testing of this system should focus on new amputees and lower mobility users (e.g., Medicare Functional Classification Level K1 and K2 prosthesis users). Furthermore, commercial implementation of the bimodal ankle-foot system should include a robust control system that can automatically switch between modes based on the user’s activity.

Background There are many epidemiological pieces of evidence that show IPF patients have the highest risk of lung cancer. We conducted a systematic review of all published data to define the characteristics of lung cancer that develops in IPF by performing a meta-analysis. Method This study was performed based on the PRISMA guideline. Documents gathered by searching through the Web of Sciences, Scopus, PubMed/Medline, OVID, and COCHRANE databases which published before 03/25/2018 that related to lung cancer in IPFs’ patients. Articles were searched using standard keywords as well as Mesh and Mesh Entry and all probabilistic combinations of words using Boolean operators. Data searching, extracting and quality appraising were done by two researchers, independently. At last, Random-effects size based on Cochrane test and I2 were used. The review protocol has been registered in PROSPERO with ID: CRD42018094037. Results Based on the meta-analysis conducted in 35 (0.18%) included studies, the total sample size of patients with IPF was estimated 131947 among whom 6384 had LC. The total rate of LC prevalence in IPF patients was estimated to be 13.54% (95% CI: 10.43–17.4) that was significantly 9 times higher in men vs. Women and smoker vs. non-smoker. Highest to lowest prevalence of cellular (histological) subtypes of lung cancer in IPF were SQCC (37.82%), ADC (30.79%), SmCC (20.48%), LCC (5.21%), and ADQC (4.81%), respectively. The highest and lowest stage of lung cancer in IPF patients was estimated at III and II, respectively. The highest involvement location of lung cancer in IPF patients was in the Peripheral. Also, the prevalence of the tumor region involved from the highest to the lowest was estimated to be in the RLL, LLL, RUL and LUL regions. Conclusions Lung cancer in IPF, most commonly SQCC, presents in elderly heavy smokers with a male, locating in peripheral regions and the lower part of lung predominance.

Here, we investigated whether explicit feedback on the result of the action (success or failure) modified sense of agency (SoA) in a continuous action task. Participants carried a white dot with a delay to a target square while avoiding obstacle squares. The color of the target changed unpredictably between white and blue. A trial was considered as successful or failed if the dot reached the target while it was white or blue. Thus, actions during the task resulted in almost identical experiences of successful and failed trials. After each trial, the participants reported to what extent they felt that they had been in control of the dot. The results showed that SoA was higher with shorter delay (i.e., easier control) and in the successful trials. These findings indicate that the sense of online control and the evaluation of continuous action based on feedback independently influence SoA. Particularly, the evaluation retrospectively modulated SoA.

Background Schistosomiasis is a snail-borne parasitic disease and is endemic in many tropical and subtropical countries. Biomphalaria straminea, an intermediate host for Schistosoma mansoni, is native to the southeastern part of South America and has established in other regions of South America, Central America and southern China during the last decades. S. mansoni is endemic in Africa, the Middle East, South America and the Caribbean. Knowledge of the potential global distribution of this snail is essential for risk assessment, monitoring, disease prevention and control. Methods and findings A comprehensive database of cross-continental occurrence for B. straminea was compiled to construct ecological models. We used several approaches to investigate the distribution of B. straminea, including direct comparison of climatic conditions, principal component analysis and niche overlap analyses to detect niche shifts. We also investigated the impacts of bioclimatic and human factors, and then used the bioclimatic and footprint layers to predict the potential distribution of B. straminea at global scale. We detected niche shifts accompanying the invasions of B. straminea in the Americas and China. The introduced populations had enlarged its habitats to subtropical regions where annual mean temperature is relatively low. Annual mean temperature, isothermality and temperature seasonality were identified as most important climatic features for the occurrence of B. straminea. Additionally, human factors improved the model prediction (P, Author summary Biomphalaria straminea is an intermediate host of Schistosoma mansoni. This snail has not only established in peripheral countries but also survived in different water habitats in Hong Kong and adjacent cities of mainland China. Ecological niche models were used to predict the potential global distribution of B. straminea. Our results showed that there were niche shifts in the process of invasion for B. straminea in the Americas and China. This snail has expanded its habitats to subtropical regions with lower annual mean temperature. Annual mean temperature, isothermality, temperature seasonality and human influence were identified as most important climatic features for the occurrence of B. straminea. Under current climate conditions the distribution of this snail should be mostly confined to the tropic and subtropic regions, including South America, Central America, Sub-Saharan Africa and Southeast Asia. With the rapid globalization and the continued burden of imported cases of S. mansoni to non-endemic countries, predicting the potential distribution of the intermediate host and its drivers is increasing in importance for designing control strategies and optimizing use of limited public health resources. Prioritizing surveillance and control efforts to high-traffic regions with high habitat suitability may be the most effective approach.

We surveyed 807 researchers (494 ecologists and 313 evolutionary biologists) about their use of Questionable Research Practices (QRPs), including cherry picking statistically significant results, p hacking, and hypothesising after the results are known (HARKing). We also asked them to estimate the proportion of their colleagues that use each of these QRPs. Several of the QRPs were prevalent within the ecology and evolution research community. Across the two groups, we found 64% of surveyed researchers reported they had at least once failed to report results because they were not statistically significant (cherry picking); 42% had collected more data after inspecting whether results were statistically significant (a form of p hacking) and 51% had reported an unexpected finding as though it had been hypothesised from the start (HARKing). Such practices have been directly implicated in the low rates of reproducible results uncovered by recent large scale replication studies in psychology and other disciplines. The rates of QRPs found in this study are comparable with the rates seen in psychology, indicating that the reproducibility problems discovered in psychology are also likely to be present in ecology and evolution.

Background Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve pharmacodynamics target when comparing with intermittent bolus (IB). However, the clinical outcomes between two groups remain inconclusive. Objective To evaluate current published literatures by meta-analysis to ascertain whether PI of meropenem can improve clinical outcomes. Methods Medline, Cochrane database and EMBASE were searched. Randomized control trails (RCT) and observational studies which compared the clinical outcomes of PI and IB groups were included and evaluated for quality. The data of studies were extracted and meta-analysis was performed using Revman 5.3 software. Results Six RCTs and 4 observation studies with relatively high quality were included in this analysis. Compared to IB group, PI group had a higher clinical success rate (odd ratio 2.10, 95% confidence interval 1.31–3.38) and a lower mortality (risk ratio 0.66, 95% confidence interval 0.50–0.88). The sensitivity analysis showed the results were stable. Conclusion PI of meropenem was associated with a higher clinical improvement rate and a lower mortality. It is recommended for patients with severe infection or infected by less sensitive microbial.

Railway seat inventory control aims to maximize ticket sale profits by determining a selling policy on the reservation horizon. This paper introduces a dynamic bid price approach in railway seat inventory control problem. Multi-dimensional demand is taken into consideration in modeling the problem, in which passenger transfer is our main focus. A new approximate approach is designed to this problem. Numerical examples are presented to evaluate the efficiency of this approach. Simulation experiments are conducted to verify the impact of transfer under different scenarios.

Nonlinear vibration systems with adjustable stiffness property have attracted considerable attentions for their prominent broadband performances. In the present manuscript, we consider the stochastic dynamical systems with adjustable stiffness and proposed a numerical method for the random responses analysis of the Gaussian white noise excited systems. A multi-dimensional Fokker-Plank-Kolmogorov equation governing the joint probability density of the mechanical states is derived according to the theory of diffusion processes. We solve the multi-dimensional equation using a splitting method and obtained the stationary probability densities and the mean-square responses directly. Two classical nonlinear vibration systems with adjustable stiffness, including the energy harvesting system and the Duffing system with Dahl friction, are presented as examples. Their comparisons with the results from Monte-Carlo simulations illustrate the effectiveness of the proposed procedure for both monostable and bistable cases, even for cases with strong excitation. In addition, the splitting method is efficient for higher-dimensional problem and has advantages of simple implementation, less storage of intermediate values and so on. Hence, in terms of the application scope, the proposed procedure is superior to the current mainstream methods for the random response evaluation of nonlinear vibration systems with adjustable stiffness.

Angiopoietin-like 4 (ANGPTL4) is a potential anti-apoptotic agent for various cells. We examined the protective effect of ANGPTL4 on hypoxia/serum deprivation (SD)-induced apoptosis of MSCs, as well as the possible mechanisms. MSCs were obtained from rat bone marrow and cultured in vitro. Apoptosis was induced by hypoxia/SD for up to 24 hr, and assessed by flow cytometry and TUNEL assay. Expression levels of Akt, ERK1/2, focal adhesion kinase (FAK), Src, Bcl-2, Bax, cytochrome C and cleaved caspase-3 were detected by Western blotting. Integrin β1 mRNA was detected by qRT-PCR. Mitochondrial membrane potential was assayed using a membrane-permeable dye. Hypoxia/SD-induced apoptosis was significantly attenuated by recombinant rat ANGPTL4 in a concentration dependent manner. Moreover, ANGPTL4 decreased the hypoxia/SD-induced caspase-3 cleavage and the cytochrome C release, but increased the Bcl-2/Bax ratio and the mitochondrial membrane potential. Decreased expression of integrin β1, the ANGPTL4 receptor was observed during hypoxia/SD conditions, however, such decrease was reversed by ANGPTL4. In addition, ANGPTL4 induced integrin β1-associated FAK and Src phosphorylation, which was blocked by anti-integrin β1 antibody. ANGPTL4 also reversed the hypoxia/SD-induced decrease of Akt and ERK 1/2 phosphorylation, and the effect of ANGPTL4 was abolished by inhibitors of either integrins, ERK1/2, or phosphatidylinositol 3-kinase (PI3K). Blocking integrinβ1, Akt or ERK largely attenuated anti-apoptotic effect of ANGPTL4. ANGPTL4 protects MSCs from hypoxia/SD-induced apoptosis by interacting with integrins to stimulate FAK complex, leading to downstream ERK1/2 and PI3K/Akt signaling pathways and mimicking the pathway in which MSCs contact with the extracellular matrix.

In plant breeding, one of the main purpose of multi-environment trial (MET) is to assess the intensity of genotype-by-environment (G×E) interactions in order to select high-performing lines of each environment. Most models to analyze such MET data consider only the additive genetic effects and the part of the non-additive genetic effects are confounded with the residual terms and this may lead to the non-negligible residual covariances between the same trait measured at multiple environments. In breeding programs it is also common to have the phenotype information from some environments available and values are missing in some other environments. In this study we focused on two problems: (1) to study the impact of different residual covariance structures on genomic prediction ability using different models to analyze MET data; (2) to compare the ability of different MET analysis models to predict the missing values in a single environment. Our results suggests that, it is important to consider the heterogeneous residual covariance structure for the MET analysis and multivariate mixed model seems to be especially suitable to predict the missing values in a single environment. We also present the prediction abilities based on Bayesian and frequentist approaches with different models using field data sets (maize and rice) having different levels of G×E interactions.

Arterial stiffness, typically assessed as the aortic pulse wave velocity (PWV), and central blood pressure levels may be indicators of cardiovascular disease (CVD) risk. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) obtained baseline assessments (at randomization) of PWV and central systolic blood pressure (C-SBP) to: 1) characterize these vascular measurements in the SPRINT cohort, and 2) test the hypotheses that PWV and C-SBP are associated with glucose homeostasis and markers of chronic kidney disease (CKD). The SphygmoCor® CPV device was used to assess carotid-femoral PWV and its pulse wave analysis study protocol was used to obtain C-SBP. Valid results were obtained from 652 participants. Mean (±SD) PWV and C-SBP for the SPRINT cohort were 10.7 ± 2.7 m/s and 132.0 ± 17.9 mm Hg respectively. Linear regression analyses for PWV and C-SBP results adjusted for age, sex, and race/ethnicity in relation to several markers of glucose homeostasis and CKD did not identify any significant associations with the exception of a marginally statistically significant and modest association between PWV and urine albumin-to-creatinine ratio (linear regression estimate ± SE, 0.001 ± 0.0006; P-value 0.046). In a subset of SPRINT participants, PWV was significantly higher than in prior studies of normotensive persons, as expected. For older age groups in the SPRINT cohort (age > 60 years), PWV was compared with a reference population of hypertensive individuals. There were no compelling associations noted between PWV or C-SBP and markers of glucose homeostasis or CKD.Clinical trial registrationNCT01206062.

The ability of winter wheat (Triticum aestivum L.) plants to develop freezing tolerance through cold acclimation is a complex rait that responds to many environmental cues including day length and temperature. A large part of the freezing tolerance is conditioned by the C-repeat binding factor (CBF) gene regulon. We investigated whether the level of freezing tolerance of 12 winter wheat lines varied throughout the day and night in plants grown under a constant low temperature and a 12-hour photoperiod. Freezing tolerance was significantly greater (P

Background Vascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs. Results We demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure. Conclusions Together, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.

Demands on visuospatial working memory are a ubiquitous part of everyday life. As such, significant efforts have been made to understand how the brain responds to these demands in real-world environments. Multiple brain imaging studies have highlighted a fronto-parietal cortical network that underlies visuospatial working memory, is modulated by cognitive load, and that appears to respond uniquely to encoding versus retrieval components. Furthermore, multiple studies have identified functional connectivity in regions of the fronto-parietal network during working memory tasks. Together, these findings have helped outline important aspects of the neural architecture that underlies visuospatial working memory. Here, we provide results from the first fNIRS-based investigation of fronto-parietal signatures of cortical activation and functional connectivity during a computer-based visuospatial working memory task. Our results indicate that the local maxima of cortical activation and functional coherence do not necessarily overlap spatially, and that cortical activation is significantly more susceptible to task-specific demands compared to functional connectivity. These results highlight important and novel information regarding neurotypical signatures of cortical activation and functional connectivity during visuospatial working memory. Our findings also demonstrate the utility of fNIRS for interrogating these cognitive processes.

Background Small randomized controlled studies and meta-analyses have shown that thrombolysis, especially catheter-directed thrombolysis, can reduce the incidence of post-thrombotic syndrome (PTS). However, the recent ATTRACT trial did not demonstrate the same effects. Given this confusing situation, we performed an updated meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of thrombolysis, especially catheter-directed thrombolysis, on the outcomes of deep venous thrombosis (DVT). Methods We searched PubMed, Embase, and the Cochrane Library for relevant studies comparing thrombolysis in combination with anticoagulation and with anticoagulation alone. The primary endpoint was PTS during the longest follow-up period. The safety endpoint was the incidence of major bleeding events. We also evaluated the outcomes of catheter-directed thrombolysis as a subgroup analysis. Results Six RCTs, including 1418 patients with DVT, were included in our meta-analysis. Thrombolysis in combination with anticoagulation did not reduce PTS (RR: 0.90, [0.80–1.01], P = 0.19) and increased major bleeding (RR: 2.07, [1.12–3.81], P = 0.02). However, trial sequential analysis (TSA) showed that more patients are needed to support the conclusion that thrombolysis in combination with anticoagulation increased major bleeding. Catheter-directed thrombolysis did not reduce the incidence of PTS (RR: 0.88, [0.68–1.13], P = 0.31) and did increase the incidence of major bleeding events (RR: 1.89, [1.00–3.59], P = 0.05). Conclusion Thrombolysis, including catheter-directed thrombolysis, did not reduce the incidence of PTS and increased the incidence of major bleeding. However, the results were not supported by TSA and sensitivity analysis, so more relevant studies are needed.

The goal of this study was to assess the adherence of primary open-angle glaucoma (POAG) patients to medication, and to determine co-factors influencing adherence, using a representative sample of members of the largest German public health insurer. The observational cohort study was based on a longitudinal data set from 2010–2013 and included 250,000 insured persons aged 50 and older with 10,120 diagnosed POAG patients. Uni- and multivariate analysis was performed to investigate several aspects of glaucoma, such as prevalence, adherence, and co-factors influencing adherence. The main outcome measured adherence with prescriptions filled within a year. Multivariate panel regression analysis was used to determine the co-factors influencing this adherence. Prevalence of POAG was 3.36% [CI: 3.28–3.43%], with 2.91% [CI: 2.81–3.01%] for males and 3.71% [CI: 3.61–3.81%] for females, increasing with age. The mean level of adherence in terms of prescriptions filled was 66.5% [CI: 65.50–67.60%]. The results of this analysis revealed a significant influence of age, duration of the disease, care need, distance to death, and multimorbidity as co-factors of non-adherence, whereas gender had no influence. The analysis provided detailed information about POAG health care aspects concerning prevalence and adherence. The most endangered risk groups for non-adherence were patients aged 50–59, patients older than 80 years, patients with a longer duration of POAG, patients with care needs, and patients with three or more severe diseases in addition to glaucoma. To know the predictors responsible for an increased risk to develop POAG is of importance for all persons involved in health care management. Therefore effective strategies to increase awareness of patients and medical care personnel about non-adherence and the importance of a regular and continuous medication to avoid further nerve fiber damage and possible blindness have to be developed.

Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits—hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)—in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk.

Introduction This study aimed to determine the diagnostic accuracy of adding copeptin to cardiac troponin (cTn) on admission to the emergency department (ED) for non-ST elevation myocardial infarction (NSTEMI) compared to cTn alone. Materials and methods A literature search of MEDLINE, EMBASE, and the Cochrane Library was performed (search date: April 13, 2018). Primary studies were included if they accurately reported on patients with symptoms suggestive of acute myocardial infarction and measured both cTn alone and cTn with copeptin upon admission to the ED. The patients with evidence of ST elevation myocardial infarction were excluded. To assess the risk of bias for the included studies, the QUADAS-2 tool was used. Results The study participants included a total of 7,998 patients from 14 observational studies. The addition of copeptin to cTn significantly improved the sensitivity (0.81 [0.74 to 0.87] vs. 0.92 [0.89 to 0.95], respectively, p