The 100 most-cited articles in PLoS ONE, 2016

Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7-15·1%), and stages 3-5 was 10·6%(9·2-12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8-4·2%); Stage-2 (eGFR 60-89+ACR>30):…

FASTA and FASTQ are basic and ubiquitous formats for storing nucleotide and protein sequences. Common manipulations of FASTA/Q file include converting, searching, filtering, deduplication, splitting, shuffling, and sampling. Existing tools only implement some of these manipulations, and not particularly efficiently, and some are only available for certain operating systems. Furthermore, the complicated installation process of required packages and running environments can render these programs less user friendly. This paper describes a cross-platform ultrafast comprehensive toolkit for FASTA/Q processing. SeqKit provides executable binary files for all major operating systems, including Windows, Linux, and Mac OSX, and can be directly used without any dependencies or pre-configurations. SeqKit demonstrates competitive performance in execution time and memory usage compared to similar tools. The efficiency and usability of SeqKit enable researchers to rapidly accomplish common FASTA/Q file manipulations. SeqKit is open source and available on Github at…

Blockchain is a decentralized transaction and data management technology developed first for Bitcoin cryptocurrency. The interest in Blockchain technology has been increasing since the idea was coined in 2008. The reason for the interest in Blockchain is its central attributes that provide security, anonymity and data integrity without any third party organization in control of the transactions, and therefore it creates interesting research areas, especially from the perspective of technical challenges and limitations. In this research, we have conducted a systematic mapping study with the goal of collecting all relevant research on Blockchain technology. Our objective is to understand the current research topics, challenges and future directions regarding Blockchain technology from the technical perspective. We have extracted 41 primary papers from scientific databases. The results show that focus in over 80% of the papers is on Bitcoin system and less than 20% deals with other Blockchain applications including e.g. smart contracts and licensing. The majority of research is…

BACKGROUND: Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. We present the latest CS rates and trends over the last 24 years. METHODS: We collected nationally-representative data on CS rates between 1990 to 2014 and calculated regional and subregional weighted averages. We conducted a longitudinal analysis calculating differences in CS rates as absolute change and as the average annual rate of increase (AARI). RESULTS: According to the latest data from 150 countries, currently 18.6% of all births occur by CS, ranging from 6% to 27.2% in the least and most developed regions, respectively. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%). Based on the data from 121 countries, the trend analysis showed that between 1990 and 2014, the global average CS rate increased 12.4% (from 6.7% to 19.1%) with an…

The fall armyworm Spodoptera frugiperda is a prime noctuid pest of maize on the American continents where it has remained confined despite occasional interceptions by European quarantine services in recent years. The pest has currently become a new invasive species in West and Central Africa where outbreaks were recorded for the first time in early 2016. The presence of at least two distinct haplotypes within samples collected on maize in Nigeria and São Tomé suggests multiple introductions into the African continent. Implications of this new threat to the maize crop in tropical Africa are briefly discussed.

OBJECTIVE: To determine whether there is an association between healthcare professionals' wellbeing and burnout, with patient safety. DESIGN: Systematic research review. DATA SOURCES: PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. RESULTS: Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an…

The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I…

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot…

Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore,…

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to…

BACKGROUND: Several R packages exist for the detection of differentially expressed genes from RNA-Seq data. The analysis process includes three main steps, namely normalization, dispersion estimation and test for differential expression. Quality control steps along this process are recommended but not mandatory, and failing to check the characteristics of the dataset may lead to spurious results. In addition, normalization methods and statistical models are not exchangeable across the packages without adequate transformations the users are often not aware of. Thus, dedicated analysis pipelines are needed to include systematic quality control steps and prevent errors from misusing the proposed methods. RESULTS: SARTools is an R pipeline for differential analysis of RNA-Seq count data. It can handle designs involving two or more conditions of a single biological factor with or without a blocking factor (such as a batch effect or a sample pairing). It is based on DESeq2 and edgeR and is composed of an R package and two R script templates (for DESeq2 and edgeR respectively). Tuning a…

Large volumes of gridded climate data have become available in recent years including interpolated historical data from weather stations and future predictions from general circulation models. These datasets, however, are at various spatial resolutions that need to be converted to scales meaningful for applications such as climate change risk and impact assessments or sample-based ecological research. Extracting climate data for specific locations from large datasets is not a trivial task and typically requires advanced GIS and data management skills. In this study, we developed a software package, ClimateNA, that facilitates this task and provides a user-friendly interface suitable for resource managers and decision makers as well as scientists. The software locally downscales historical and future monthly climate data layers into scale-free point estimates of climate values for the entire North American continent. The software also calculates a large number of biologically relevant climate variables that are usually derived from daily weather data. ClimateNA covers 1) 104 years of…

Food production is a major driver of greenhouse gas (GHG) emissions, water and land use, and dietary risk factors are contributors to non-communicable diseases. Shifts in dietary patterns can therefore potentially provide benefits for both the environment and health. However, there is uncertainty about the magnitude of these impacts, and the dietary changes necessary to achieve them. We systematically review the evidence on changes in GHG emissions, land use, and water use, from shifting current dietary intakes to environmentally sustainable dietary patterns. We find 14 common sustainable dietary patterns across reviewed studies, with reductions as high as 70-80% of GHG emissions and land use, and 50% of water use (with medians of about 20-30% for these indicators across all studies) possible by adopting sustainable dietary patterns. Reductions in environmental footprints were generally proportional to the magnitude of animal-based food restriction. Dietary shifts also yielded modest benefits in all-cause mortality risk. Our review reveals that environmental and health benefits are…

Anomaly detection is the process of identifying unexpected items or events in datasets, which differ from the norm. In contrast to standard classification tasks, anomaly detection is often applied on unlabeled data, taking only the internal structure of the dataset into account. This challenge is known as unsupervised anomaly detection and is addressed in many practical applications, for example in network intrusion detection, fraud detection as well as in the life science and medical domain. Dozens of algorithms have been proposed in this area, but unfortunately the research community still lacks a comparative universal evaluation as well as common publicly available datasets. These shortcomings are addressed in this study, where 19 different unsupervised anomaly detection algorithms are evaluated on 10 different datasets from multiple application domains. By publishing the source code and the datasets, this paper aims to be a new well-funded basis for unsupervised anomaly detection research. Additionally, this evaluation reveals the strengths and weaknesses of the different…

Drought has been a major cause of agricultural disaster, yet how it affects the vulnerability of maize and wheat production in combination with several co-varying factors (i.e., phenological phases, agro-climatic regions, soil texture) remains unclear. Using a data synthesis approach, this study aims to better characterize the effects of those co-varying factors with drought and to provide critical information on minimizing yield loss. We collected data from peer-reviewed publications between 1980 and 2015 which examined maize and wheat yield responses to drought using field experiments. We performed unweighted analysis using the log response ratio to calculate the bootstrapped confidence limits of yield responses and calculated drought sensitivities with regards to those co-varying factors. Our results showed that yield reduction varied with species, with wheat having lower yield reduction (20.6%) compared to maize (39.3%) at approximately 40% water reduction. Maize was also more sensitive to drought than wheat, particularly during reproductive phase and equally sensitive in the…

The U.S. health care sector is highly interconnected with industrial activities that emit much of the nation's pollution to air, water, and soils. We estimate emissions directly and indirectly attributable to the health care sector, and potential harmful effects on public health. Negative environmental and public health outcomes were estimated through economic input-output life cycle assessment (EIOLCA) modeling using National Health Expenditures (NHE) for the decade 2003-2013 and compared to national totals. In 2013, the health care sector was also responsible for significant fractions of national air pollution emissions and impacts, including acid rain (12%), greenhouse gas emissions (10%), smog formation (10%) criteria air pollutants (9%), stratospheric ozone depletion (1%), and carcinogenic and non-carcinogenic air toxics (1-2%). The largest contributors to impacts are discussed from both the supply side (EIOLCA economic sectors) and demand side (NHE categories), as are trends over the study period. Health damages from these pollutants are estimated at 470,000 DALYs lost from…

OBJECTIVE: We aimed to collect and meta-analyse the existing evidence regarding the performance of the Center for Epidemiologic Studies Depression (CES-D) for detecting depression in general population and primary care settings. METHOD: Systematic literature search in PubMed and PsychINFO. Eligible studies were: a) validation studies of screening questionnaires with information on the accuracy of the CES-D; b) samples from general populations or primary care settings; c) standardized diagnostic interviews following standard classification systems used as gold standard; and d) English or Spanish language of publication. Pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratio were estimated for several cut-off points using bivariate mixed effects models for each threshold. The summary receiver operating characteristic curve was estimated with Rutter and Gatsonis mixed effects models; area under the curve was calculated. Quality of the studies was assessed with the QUADAS tool. Causes of heterogeneity were evaluated with the Rutter and Gatsonis mixed effects model…

Accurate predictions of crop yield are critical for developing effective agricultural and food policies at the regional and global scales. We evaluated a machine-learning method, Random Forests (RF), for its ability to predict crop yield responses to climate and biophysical variables at global and regional scales in wheat, maize, and potato in comparison with multiple linear regressions (MLR) serving as a benchmark. We used crop yield data from various sources and regions for model training and testing: 1) gridded global wheat grain yield, 2) maize grain yield from US counties over thirty years, and 3) potato tuber and maize silage yield from the northeastern seaboard region. RF was found highly capable of predicting crop yields and outperformed MLR benchmarks in all performance statistics that were compared. For example, the root mean square errors (RMSE) ranged between 6 and 14% of the average observed yield with RF models in all test cases whereas these values ranged from 14% to 49% for MLR models. Our results show that RF is an effective and versatile machine-learning method for…

Delayed or impaired language development is a common developmental concern, yet there is little agreement about the criteria used to identify and classify language impairments in children. Children's language difficulties are at the interface between education, medicine and the allied professions, who may all adopt different approaches to conceptualising them. Our goal in this study was to use an online Delphi technique to see whether it was possible to achieve consensus among professionals on appropriate criteria for identifying children who might benefit from specialist services. We recruited a panel of 59 experts representing ten disciplines (including education, psychology, speech-language therapy/pathology, paediatrics and child psychiatry) from English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom and USA). The starting point for round 1 was a set of 46 statements based on articles and commentaries in a special issue of a journal focusing on this topic. Panel members rated each statement for both relevance and validity on a seven-point scale, and…

Rice blast is one of the most destructive diseases affecting rice worldwide. The adoption of host resistance has proven to be the most economical and effective approach to control rice blast. In recent years, sequence-specific nucleases (SSNs) have been demonstrated to be powerful tools for the improvement of crops via gene-specific genome editing, and CRISPR/Cas9 is thought to be the most effective SSN. Here, we report the improvement of rice blast resistance by engineering a CRISPR/Cas9 SSN (C-ERF922) targeting the OsERF922 gene in rice. Twenty-one C-ERF922-induced mutant plants (42.0%) were identified from 50 T0 transgenic plants. Sanger sequencing revealed that these plants harbored various insertion or deletion (InDel) mutations at the target site. We showed that all of the C-ERF922-induced allele mutations were transmitted to subsequent generations. Mutant plants harboring the desired gene modification but not containing the transferred DNA were obtained by segregation in the T1 and T2 generations. Six T2 homozygous mutant lines were further examined for a blast resistance…

There is great interest in the restoration and conservation of coastal habitats for protection from flooding and erosion. This is evidenced by the growing number of analyses and reviews of the effectiveness of habitats as natural defences and increasing funding world-wide for nature-based defences-i.e. restoration projects aimed at coastal protection; yet, there is no synthetic information on what kinds of projects are effective and cost effective for this purpose. This paper addresses two issues critical for designing restoration projects for coastal protection: (i) a synthesis of the costs and benefits of projects designed for coastal protection (nature-based defences) and (ii) analyses of the effectiveness of coastal habitats (natural defences) in reducing wave heights and the biophysical parameters that influence this effectiveness. We (i) analyse data from sixty-nine field measurements in coastal habitats globally and examine measures of effectiveness of mangroves, salt-marshes, coral reefs and seagrass/kelp beds for wave height reduction; (ii) synthesise the costs and coastal…

Palm oil is the most widely traded vegetable oil globally, with demand projected to increase substantially in the future. Almost all oil palm grows in areas that were once tropical moist forests, some of them quite recently. The conversion to date, and future expansion, threatens biodiversity and increases greenhouse gas emissions. Today, consumer pressure is pushing companies toward deforestation-free sources of palm oil. To guide interventions aimed at reducing tropical deforestation due to oil palm, we analysed recent expansions and modelled likely future ones. We assessed sample areas to find where oil palm plantations have recently replaced forests in 20 countries, using a combination of high-resolution imagery from Google Earth and Landsat. We then compared these trends to countrywide trends in FAO data for oil palm planted area. Finally, we assessed which forests have high agricultural suitability for future oil palm development, which we refer to as vulnerable forests, and identified critical areas for biodiversity that oil palm expansion threatens. Our analysis reveals…

Reflective functioning or mentalizing is the capacity to interpret both the self and others in terms of internal mental states such as feelings, wishes, goals, desires, and attitudes. This paper is part of a series of papers outlining the development and psychometric features of a new self-report measure, the Reflective Functioning Questionnaire (RFQ), designed to provide an easy to administer self-report measure of mentalizing. We describe the development and initial validation of the RFQ in three studies. Study 1 focuses on the development of the RFQ, its factor structure and construct validity in a sample of patients with Borderline Personality Disorder (BPD) and Eating Disorder (ED) (n = 108) and normal controls (n = 295). Study 2 aims to replicate these findings in a fresh sample of 129 patients with personality disorder and 281 normal controls. Study 3 addresses the relationship between the RFQ, parental reflective functioning and infant attachment status as assessed with the Strange Situation Procedure (SSP) in a sample of 136 community mothers and their infants. In both…

Most traits of agronomic importance are quantitative in nature, and genetic markers have been used for decades to dissect such traits. Recently, genomic selection has earned attention as next generation sequencing technologies became feasible for major and minor crops. Mixed models have become a key tool for fitting genomic selection models, but most current genomic selection software can only include a single variance component other than the error, making hybrid prediction using additive, dominance and epistatic effects unfeasible for species displaying heterotic effects. Moreover, Likelihood-based software for fitting mixed models with multiple random effects that allows the user to specify the variance-covariance structure of random effects has not been fully exploited. A new open-source R package called sommer is presented to facilitate the use of mixed models for genomic selection and hybrid prediction purposes using more than one variance component and allowing specification of covariance structures. The use of sommer for genomic prediction is demonstrated through several…

As breaking news unfolds people increasingly rely on social media to stay abreast of the latest updates. The use of social media in such situations comes with the caveat that new information being released piecemeal may encourage rumours, many of which remain unverified long after their point of release. Little is known, however, about the dynamics of the life cycle of a social media rumour. In this paper we present a methodology that has enabled us to collect, identify and annotate a dataset of 330 rumour threads (4,842 tweets) associated with 9 newsworthy events. We analyse this dataset to understand how users spread, support, or deny rumours that are later proven true or false, by distinguishing two levels of status in a rumour life cycle i.e., before and after its veracity status is resolved. The identification of rumours associated with each event, as well as the tweet that resolved each rumour as true or false, was performed by journalist members of the research team who tracked the events in real time. Our study shows that rumours that are ultimately proven true tend to be…

CONTEXT: The concept of citizen science (CS) is currently referred to by many actors inside and outside science and research. Several descriptions of this purportedly new approach of science are often heard in connection with large datasets and the possibilities of mobilizing crowds outside science to assists with observations and classifications. However, other accounts refer to CS as a way of democratizing science, aiding concerned communities in creating data to influence policy and as a way of promoting political decision processes involving environment and health. OBJECTIVE: In this study we analyse two datasets (N = 1935, N = 633) retrieved from the Web of Science (WoS) with the aim of giving a scientometric description of what the concept of CS entails. We account for its development over time, and what strands of research that has adopted CS and give an assessment of what scientific output has been achieved in CS-related projects. To attain this, scientometric methods have been combined with qualitative approaches to render more precise search terms. RESULTS: Results…

BACKGROUND: Insulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR. METHODS: We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters--such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios--was analyzed to identify IR. RESULTS: For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin…

A novel intrusion detection system (IDS) using a deep neural network (DNN) is proposed to enhance the security of in-vehicular network. The parameters building the DNN structure are trained with probability-based feature vectors that are extracted from the in-vehicular network packets. For a given packet, the DNN provides the probability of each class discriminating normal and attack packets, and, thus the sensor can identify any malicious attack to the vehicle. As compared to the traditional artificial neural network applied to the IDS, the proposed technique adopts recent advances in deep learning studies such as initializing the parameters through the unsupervised pre-training of deep belief networks (DBN), therefore improving the detection accuracy. It is demonstrated with experimental results that the proposed technique can provide a real-time response to the attack with a significantly improved detection ratio in controller area network (CAN) bus.

Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P<0.001, Q = 0.002) when BMI was > 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P<0.001, Q<0.001). However, in women, it remained unchanged within the different ranges of BMI. We observed a higher presence of Veillonella (84.6% vs. 47.2%; X2 test P = 0.001, Q = 0.019) and Methanobrevibacter genera (84.6% vs. 47.2%; X2 test P…

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer…

Individual's decisions, from what product to buy to whether to engage in risky behavior, often depend on the choices, behaviors, or states of other people. People, however, rarely have global knowledge of the states of others, but must estimate them from the local observations of their social contacts. Network structure can significantly distort individual's local observations. Under some conditions, a state that is globally rare in a network may be dramatically over-represented in the local neighborhoods of many individuals. This effect, which we call the "majority illusion," leads individuals to systematically overestimate the prevalence of that state, which may accelerate the spread of social contagions. We develop a statistical model that quantifies this effect and validate it with measurements in synthetic and real-world networks. We show that the illusion is exacerbated in networks with a heterogeneous degree distribution and disassortative structure.

Recent work suggests that hair cells are not the most vulnerable elements in the inner ear; rather, it is the synapses between hair cells and cochlear nerve terminals that degenerate first in the aging or noise-exposed ear. This primary neural degeneration does not affect hearing thresholds, but likely contributes to problems understanding speech in difficult listening environments, and may be important in the generation of tinnitus and/or hyperacusis. To look for signs of cochlear synaptopathy in humans, we recruited college students and divided them into low-risk and high-risk groups based on self-report of noise exposure and use of hearing protection. Cochlear function was assessed by otoacoustic emissions and click-evoked electrocochleography; hearing was assessed by behavioral audiometry and word recognition with or without noise or time compression and reverberation. Both groups had normal thresholds at standard audiometric frequencies, however, the high-risk group showed significant threshold elevation at high frequencies (10-16 kHz), consistent with early stages of noise…

In this wIn this work, we explore finite-dimensional linear representations of nonlinear dynamical systems by restricting the Koopman operator to an invariant subspace spanned by specially chosen observable functions. The Koopman operator is an infinite-dimensional linear operator that evolves functions of the state of a dynamical system. Dominant terms in the Koopman expansion are typically computed using dynamic mode decomposition (DMD). DMD uses linear measurements of the state variables, and it has recently been shown that this may be too restrictive for nonlinear systems. Choosing the right nonlinear observable functions to form an invariant subspace where it is possible to obtain linear reduced-order models, especially those that are useful for control, is an open challenge. Here, we investigate the choice of observable functions for Koopman analysis that enable the use of optimal linear control techniques on nonlinear problems. First, to include a cost on the state of the system, as in linear quadratic regulator (LQR) control, it is helpful to include these states in the…

The purpose of this study is to assess the psychometric properties of a French version of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), a self-report measure of posttraumatic stress disorder (PTSD) symptoms, and to further validate the existing English version of the measure. Undergraduate students (n = 838 English, n = 262 French) completed the PCL-5 as well as other self-report symptom measures of PTSD and depression online. Both the English and French versions PCL-5 total scores demonstrated excellent internal consistency (English: α = .95; French: α = .94), and strong convergent and divergent validity. Strong internal consistency was also observed for each of the four subscales for each version (α's > .79). Test-retest reliability for the French version of the measure was also very good (r = .89). Confirmatory factor analysis indicated that the four-factor DSM-5 model was not a good fit of the data. The seven-factor hybrid model best fit the data in each sample, but was only marginally superior to the six-factor anhedonia model. The French version of the PCL-5…

For nearly 100 years serotyping has been the gold standard for the identification of Salmonella serovars. Despite the increasing adoption of DNA-based subtyping approaches, serotype information remains a cornerstone in food safety and public health activities aimed at reducing the burden of salmonellosis. At the same time, recent advances in whole-genome sequencing (WGS) promise to revolutionize our ability to perform advanced pathogen characterization in support of improved source attribution and outbreak analysis. We present the Salmonella In Silico Typing Resource (SISTR), a bioinformatics platform for rapidly performing simultaneous in silico analyses for several leading subtyping methods on draft Salmonella genome assemblies. In addition to performing serovar prediction by genoserotyping, this resource integrates sequence-based typing analyses for: Multi-Locus Sequence Typing (MLST), ribosomal MLST (rMLST), and core genome MLST (cgMLST). We show how phylogenetic context from cgMLST analysis can supplement the genoserotyping analysis and increase the accuracy of in silico…

Plastic debris pervades in our oceans and freshwater systems and the potential ecosystem-level impacts of this anthropogenic litter require urgent evaluation. Microbes readily colonize aquatic plastic debris and members of these biofilm communities are speculated to include pathogenic, toxic, invasive or plastic degrading-species. The influence of plastic-colonizing microorganisms on the fate of plastic debris is largely unknown, as is the role of plastic in selecting for unique microbial communities. This work aimed to characterize microbial biofilm communities colonizing single-use poly(ethylene terephthalate) (PET) drinking bottles, determine their plastic-specificity in contrast with seawater and glass-colonizing communities, and identify seasonal and geographical influences on the communities. A substrate recruitment experiment was established in which PET bottles were deployed for 5-6 weeks at three stations in the North Sea in three different seasons. The structure and composition of the PET-colonizing bacterial/archaeal and eukaryotic communities varied with season and…

BACKGROUND: Despite accounting for approximately one fifth of all acute gastroenteritis illnesses, norovirus has received comparatively less attention than other infectious pathogens. With several candidate vaccines under development, characterizing the global economic burden of norovirus could help funders, policy makers, public health officials, and product developers determine how much attention and resources to allocate to advancing these technologies to prevent and control norovirus. METHODS: We developed a computational simulation model to estimate the economic burden of norovirus in every country/area (233 total) stratified by WHO region and globally, from the health system and societal perspectives. We considered direct costs of illness (e.g., clinic visits and hospitalization) and productivity losses. RESULTS: Globally, norovirus resulted in a total of $4.2 billion (95% UI: $3.2-5.7 billion) in direct health system costs and $60.3 billion (95% UI: $44.4-83.4 billion) in societal costs per year. Disease amongst children <5 years cost society $39.8 billion, compared to $20.4…

In this paper, we characterize major depression (MD) as a complex dynamic system in which symptoms (e.g., insomnia and fatigue) are directly connected to one another in a network structure. We hypothesize that individuals can be characterized by their own network with unique architecture and resulting dynamics. With respect to architecture, we show that individuals vulnerable to developing MD are those with strong connections between symptoms: e.g., only one night of poor sleep suffices to make a particular person feel tired. Such vulnerable networks, when pushed by forces external to the system such as stress, are more likely to end up in a depressed state; whereas networks with weaker connections tend to remain in or return to a non-depressed state. We show this with a simulation in which we model the probability of a symptom becoming 'active' as a logistic function of the activity of its neighboring symptoms. Additionally, we show that this model potentially explains some well-known empirical phenomena such as spontaneous recovery as well as accommodates existing theories about…

The dismal success rate of clinical trials for Alzheimer's disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cells derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD) patients harboring amyloid precursor protein (APP) duplication or presenilin1 (PSEN1) mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are…

Refugia have long been studied from paleontological and biogeographical perspectives to understand how populations persisted during past periods of unfavorable climate. Recently, researchers have applied the idea to contemporary landscapes to identify climate change refugia, here defined as areas relatively buffered from contemporary climate change over time that enable persistence of valued physical, ecological, and socio-cultural resources. We differentiate historical and contemporary views, and characterize physical and ecological processes that create and maintain climate change refugia. We then delineate how refugia can fit into existing decision support frameworks for climate adaptation and describe seven steps for managing them. Finally, we identify challenges and opportunities for operationalizing the concept of climate change refugia. Managing climate change refugia can be an important option for conservation in the face of ongoing climate change.

With the increasing success of hip joint replacements, the average age of patients has decreased, patients have become more active and their expectations of the implant durability have risen. Thus, pre-clinical endurance tests on hip implants require defining realistic in vivo loads from younger and more active patients. These loads require simplifications to be applicable for simulator tests and numerical analyses. Here, the contact forces in the joint were measured with instrumented hip implants in ten subjects during nine of the most physically demanding and frequent activities of daily living. Typical levels and directions of average and high joint loads were extracted from the intra- and inter-individually widely varying individual data. These data can also be used to analyse bone remodelling at the implant-bone interface, evaluate tissue straining in finite element studies or validate analytical loading predictions, among other uses. The current ISO standards for endurance tests of implant stems and necks are based on historic analytical data from the 1970s. Comparisons of…

BACKGROUND: Early adolescence (ages 10-14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes. OBJECTIVES: To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. METHODS: A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender…

Social scientists often seek to demonstrate that a construct has incremental validity over and above other related constructs. However, these claims are typically supported by measurement-level models that fail to consider the effects of measurement (un)reliability. We use intuitive examples, Monte Carlo simulations, and a novel analytical framework to demonstrate that common strategies for establishing incremental construct validity using multiple regression analysis exhibit extremely high Type I error rates under parameter regimes common in many psychological domains. Counterintuitively, we find that error rates are highest--in some cases approaching 100%--when sample sizes are large and reliability is moderate. Our findings suggest that a potentially large proportion of incremental validity claims made in the literature are spurious. We present a web application (http://jakewestfall.org/ivy/) that readers can use to explore the statistical properties of these and other incremental validity arguments. We conclude by reviewing SEM-based statistical approaches that appropriately…

Threats to and loss of seagrass ecosystems globally, impact not only natural resources but also the lives of people who directly or indirectly depend on these systems. Seagrass ecosystems play a multi-functional role in human well-being, e.g. food through fisheries, control of erosion and protection against floods. Quantifying these services reveals their contributions to human well-being and helps justify seagrass conservation. There has been no comprehensive assessment as to whether seagrass ecosystem services are perceived to vary over the globe or amongst genera. Our study compiles the most complete list of ecosystem services provided by seagrasses so far, including bioregional- and genus-specific information from expert opinion and published studies. Several seagrass ecosystem services vary considerably in their (known) provision across genera and over the globe. Seagrasses genera are clearly not all equal with regard to the ecosystem services they provide. As seagrass genera are not evenly distributed over all bioregions, the presence of an ecosystem service sometimes depends…

The argument that human society can decouple economic growth-defined as growth in Gross Domestic Product (GDP)-from growth in environmental impacts is appealing. If such decoupling is possible, it means that GDP growth is a sustainable societal goal. Here we show that the decoupling concept can be interpreted using an easily understood model of economic growth and environmental impact. The simple model is compared to historical data and modelled projections to demonstrate that growth in GDP ultimately cannot be decoupled from growth in material and energy use. It is therefore misleading to develop growth-oriented policy around the expectation that decoupling is possible. We also note that GDP is increasingly seen as a poor proxy for societal wellbeing. GDP growth is therefore a questionable societal goal. Society can sustainably improve wellbeing, including the wellbeing of its natural assets, but only by discarding GDP growth as the goal in favor of more comprehensive measures of societal wellbeing.

Climate change and decadal variability are impacting marine fish and invertebrate species worldwide and these impacts will continue for the foreseeable future. Quantitative approaches have been developed to examine climate impacts on productivity, abundance, and distribution of various marine fish and invertebrate species. However, it is difficult to apply these approaches to large numbers of species owing to the lack of mechanistic understanding sufficient for quantitative analyses, as well as the lack of scientific infrastructure to support these more detailed studies. Vulnerability assessments provide a framework for evaluating climate impacts over a broad range of species with existing information. These methods combine the exposure of a species to a stressor (climate change and decadal variability) and the sensitivity of species to the stressor. These two components are then combined to estimate an overall vulnerability. Quantitative data are used when available, but qualitative information and expert opinion are used when quantitative data is lacking. Here we conduct a climate…

BACKGROUND: A longstanding goal in regenerative medicine is to reconstitute functional tissues or organs after injury or disease. Attention has focused on the identification and relative contribution of tissue specific stem cells to the regeneration process. Relatively little is known about how the physiological process is regulated by other tissue constituents. Numerous injury models are used to investigate tissue regeneration, however, these models are often poorly understood. Specifically, for skeletal muscle regeneration several models are reported in the literature, yet the relative impact on muscle physiology and the distinct cells types have not been extensively characterised. METHODS: We have used transgenic Tg:Pax7nGFP and Flk1GFP/+ mouse models to respectively count the number of muscle stem (satellite) cells (SC) and number/shape of vessels by confocal microscopy. We performed histological and immunostainings to assess the differences in the key regeneration steps. Infiltration of immune cells, chemokines and cytokines production was assessed in vivo by Luminex®. RESULTS:…

Most psychological studies rely on student samples. Students are usually considered as more homogenous than representative samples both within and across countries. However, little is known about the nature of the differences between student and representative samples. This is an important gap, also because knowledge about the degree of difference between student and representative samples may allow to infer from the former to the latter group. Across 59 countries and 12 personality (Big-5) and attitudinal variables we found that differences between students and general public were partly substantial, incoherent, and contradicted previous findings. Two often used cultural variables, embeddedness and intellectual autonomy, failed to explain the differences between both groups across countries. We further found that students vary as much as the general population both between and within countries. In summary, our results indicate that generalizing from students to the general public can be problematic when personal and attitudinal variables are used, as students vary mostly randomly…

OBJECTIVE: Consumers are living longer, creating more pressure on the health system and increasing their requirement for self-care of chronic conditions. Despite rapidly-increasing numbers of mobile health applications ('apps') for consumers' self-care, there is a paucity of research into consumer engagement with electronic self-monitoring. This paper presents a qualitative exploration of how health consumers use apps for health monitoring, their perceived benefits from use of health apps, and suggestions for improvement of health apps. MATERIALS AND METHODS: 'Health app' was defined as any commercially-available health or fitness app with capacity for self-monitoring. English-speaking consumers aged 18 years and older using any health app for self-monitoring were recruited for interview from the metropolitan area of Perth, Australia. The semi-structured interview guide comprised questions based on the Technology Acceptance Model, Health Information Technology Acceptance Model, and the Mobile Application Rating Scale, and is the only study to do so. These models also facilitated…

BACKGROUND: Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data. METHODS AND FINDINGS: We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The…

OBJECTIVES: UK Biobank is a UK-wide cohort of 502,655 people aged 40-69, recruited from National Health Service registrants between 2006-10, with healthcare data linkage. Type 2 diabetes is a key exposure and outcome. We developed algorithms to define prevalent and incident diabetes for UK Biobank. The algorithms will be implemented by UK Biobank and their results made available to researchers on request. METHODS: We used UK Biobank self-reported medical history and medication to assign prevalent diabetes and type, and tested this against linked primary and secondary care data in Welsh UK Biobank participants. Additionally, we derived and tested algorithms for incident diabetes using linked primary and secondary care data in the English Clinical Practice Research Datalink, and ran these on secondary care data in UK Biobank. RESULTS AND SIGNIFICANCE: For prevalent diabetes, 0.001% and 0.002% of people classified as "diabetes unlikely" in UK Biobank had evidence of diabetes in their primary or secondary care record respectively. Of those classified as "probable" type 2 diabetes, 75%…

Concerns are being raised that microplastic pollution can have detrimental effects on the feeding of aquatic invertebrates, including zooplankton. Both small plastic fragments (microplastics, MPs) produced by degradation of larger plastic waste (secondary MPs; SMPs) and microscopic plastic spheres used in cosmetic products and industry (primary MPs; PMPs) are ubiquitously present in the environment. However, despite the fact that most environmental MPs consist of weathered plastic debris with irregular shape and broad size distribution, experimental studies of organism responses to MP exposure have largely used uniformly sized spherical PMPs. Therefore, effects observed for PMPs in such experiments may not be representative for MP-effects in situ. Moreover, invertebrate filter-feeders are generally well adapted to the presence of refractory material in seston, which questions the potential of MPs at environmentally relevant concentrations to measurably affect digestion in these organisms. Here, we compared responses to MPs (PMPs and SMPs) and naturally occurring particles (kaolin…

Neurovascular inflammation is a major contributor to many neurological disorders, but modeling these processes in vitro has proven to be difficult. Here, we microengineered a three-dimensional (3D) model of the human blood-brain barrier (BBB) within a microfluidic chip by creating a cylindrical collagen gel containing a central hollow lumen inside a microchannel, culturing primary human brain microvascular endothelial cells on the gel's inner surface, and flowing medium through the lumen. Studies were carried out with the engineered microvessel containing endothelium in the presence or absence of either primary human brain pericytes beneath the endothelium or primary human brain astrocytes within the surrounding collagen gel to explore the ability of this simplified model to identify distinct contributions of these supporting cells to the neuroinflammatory response. This human 3D BBB-on-a-chip exhibited barrier permeability similar to that observed in other in vitro BBB models created with non-human cells, and when stimulated with the inflammatory trigger, tumor necrosis…

BACKGROUND: Periprosthetic joint infections (PJIs) are dreaded complications of total joint arthroplasties. The risk of developing PJIs is likely to be influenced by several patient factors such as sociodemographic characteristics, body mass index (BMI), and medical and surgical histories. However, the nature and magnitude of the long-term longitudinal associations between these patient-related factors and risk of developing PJIs are uncertain. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the associations between several patient-related factors and PJI. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Cochrane Library, and reference lists of relevant studies from inception to September 2015. STUDY SELECTION: Longitudinal studies with at least one-year of follow-up for PJIs after total joint arthroplasty. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data on study characteristics, methods, and outcomes. A consensus was reached with involvement of a third. The relative risk (RR) with 95% confidence intervals was used as the summary measure of…

BACKGROUND AND AIMS: Internet addiction (IA) could be a major concern in university medical students aiming to develop into health professionals. The implications of this addiction as well as its association with sleep, mood disorders and self-esteem can hinder their studies, impact their long-term career goals and have wide and detrimental consequences for society as a whole. The objectives of this study were to: 1) Assess potential IA in university medical students, as well as factors associated with it; 2) Assess the relationships between potential IA, insomnia, depression, anxiety, stress and self-esteem. METHODS: Our study was a cross-sectional questionnaire-based survey conducted among 600 students of three faculties: medicine, dentistry and pharmacy at Saint-Joseph University. Four validated and reliable questionnaires were used: the Young Internet Addiction Test, the Insomnia Severity Index, the Depression Anxiety Stress Scales (DASS 21), and the Rosenberg Self Esteem Scale (RSES). RESULTS: The average YIAT score was 30 ± 18.474; Potential IA prevalence rate was 16.8% (95%…

Several discrete emotions have broad theoretical and empirical importance, as shown by converging evidence from diverse areas of psychology, including facial displays, developmental behaviors, and neuroscience. However, the measurement of these states has not progressed along with theory, such that when researchers measure subjectively experienced emotions, they commonly rely on scales assessing broad dimensions of affect (positivity and negativity), rather than discrete emotions. The current manuscript presents four studies that validate a new instrument, the Discrete Emotions Questionnaire (DEQ), that is sensitive to eight distinct state emotions: anger, disgust, fear, anxiety, sadness, happiness, relaxation, and desire. Emotion theory supporting the importance of distinguishing these specific emotions is reviewed.

Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence…

The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å) might still qualify as 'acceptable' with a descent Fnat (>0.50) and iRMS (<3.0Å). This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by…

BACKGROUND: A gender-based disparity in physical activity (PA) among youth, whereby girls are less active than boys is a persistent finding in the literature. A greater understanding of the mechanisms underlying this difference has potential to guide PA intervention strategies. METHODS: Data were collected at age 8 and 12 years (276 boys, 279 girls) from 29 schools as part of the LOOK study. Multilevel linear models were fitted separately for boys and girls to examine effects of individual, family and environmental level correlates on pedometer measured PA. Cardio-respiratory fitness (multi-stage run), percent fat (DEXA), eye-hand coordination (throw and catch test) and perceived competence in physical education (questionnaire) were used as individual level correlates. At the family level, parent's support and education (questionnaire) were used. School attended and extracurricular sport participation were included as environmental level correlates. RESULTS: Girls were 19% less active than boys (9420 vs 11360 steps/day, p<0.001, 95%CI [1844, 2626]). Lower PA among girls was…

BACKGROUND: Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe immunotherapy-related adverse events (irAEs) have been reported. OBJECTIVES: To conduct a systematic review of case reports describing the occurrence of irAEs in patients with cancer following checkpoint blockade therapy, primarily to identify potentially unrecognized or unusual clinical findings and toxicity. DATA SOURCES: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane CENTRAL with no restriction through August 2015. STUDY SELECTION: Studies reporting cases of cancer develop irAEs following treatment with anti CTLA-4 (ipilimumab) or anti PD-1 (nivolumab or pembrolizumab) antibodies were included. DATA EXTRACTION: We extracted data on patient characteristics, irAEs characteristics, how irAEs were managed, and their outcomes. DATA SYNTHESIS: 191 publications met inclusion criteria, reporting on 251 cases. Most patients had metastatic melanoma (95.6%), and the majority were treated…

Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type…

INTRODUCTION: Maternal and neonatal mortality remains high in many low- and middle-income countries (LMIC). Availability and use of mobile phones is increasing rapidly with 90% of persons in developing countries having a mobile-cellular subscription. Mobile health (mHealth) interventions have been proposed as effective solutions to improve maternal and neonatal health. This systematic review assessed the effect of mHealth interventions that support pregnant women during the antenatal, birth and postnatal period in LMIC. METHODS: The review was registered with Prospero (CRD42014010292). Six databases were searched from June 2014-April 2015, accompanied by grey literature search using pre-defined search terms linked to pregnant women in LMIC and mHealth. Quality of articles was assessed with an adapted Cochrane Risk of Bias Tool. Because of heterogeneity in outcomes, settings and study designs a narrative synthesis of quantitative results of intervention studies on maternal outcomes, neonatal outcomes, service utilization, and healthy pregnancy education was conducted. Qualitative and…

BACKGROUND: Use of robotic systems for minimally invasive surgery has rapidly increased during the last decade. Understanding the causes of adverse events and their impact on patients in robot-assisted surgery will help improve systems and operational practices to avoid incidents in the future. METHODS: By developing an automated natural language processing tool, we performed a comprehensive analysis of the adverse events reported to the publicly available MAUDE database (maintained by the U.S. Food and Drug Administration) from 2000 to 2013. We determined the number of events reported per procedure and per surgical specialty, the most common types of device malfunctions and their impact on patients, and the potential causes for catastrophic events such as patient injuries and deaths. RESULTS: During the study period, 144 deaths (1.4% of the 10,624 reports), 1,391 patient injuries (13.1%), and 8,061 device malfunctions (75.9%) were reported. The numbers of injury and death events per procedure have stayed relatively constant (mean = 83.4, 95% confidence interval (CI), 74.2-92.7 per…

Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added…

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder. Highly reactive oxygen free radicals are believed to be involved in the pathogenesis of the disease. In this study, RA patients were sub-grouped depending upon the presence or absence of rheumatoid factor, disease activity score and disease duration. RA Patients (120) and healthy controls (53) were evaluated for the oxidant-antioxidant status by monitoring ROS production, biomarkers of lipid peroxidation, protein oxidation and DNA damage. The level of various enzymatic and non-enzymatic antioxidants was also monitored. Correlation analysis was also performed for analysing the association between ROS and various other parameters. METHODS: Intracellular ROS formation, lipid peroxidation (MDA level), protein oxidation (carbonyl level and thiol level) and DNA damage were detected in the blood of RA patients. Antioxidant status was evaluated by FRAP assay, DPPH reduction assay and enzymatic (SOD, catalase, GST, GR) and non-enzymatic (vitamin C and GSH) antioxidants. RESULTS: RA patients showed a higher ROS…

Plant growth-promoting rhizobacteria (PGPR) may provide a biological alternative to fix atmospheric N2 and delay N remobilisation in maize plant to increase crop yield, based on an understanding that plant-N remobilisation is directly correlated to its plant senescence. Thus, four PGPR strains were selected from a series of bacterial strains isolated from maize roots at two locations in Malaysia. The PGPR strains were screened in vitro for their biochemical plant growth-promoting (PGP) abilities and plant growth promotion assays. These strains were identified as Klebsiella sp. Br1, Klebsiella pneumoniae Fr1, Bacillus pumilus S1r1 and Acinetobacter sp. S3r2 and a reference strain used was Bacillus subtilis UPMB10. All the PGPR strains were tested positive for N2 fixation, phosphate solubilisation and auxin production by in vitro tests. In a greenhouse experiment with reduced fertiliser-N input (a third of recommended fertiliser-N rate), the N2 fixation abilities of PGPR in association with maize were determined by 15N isotope dilution technique at two harvests, namely, prior to…

The Indus basin heavily depends on its upstream mountainous part for the downstream supply of water while downstream demands are high. Since downstream demands will likely continue to increase, accurate hydrological projections for the future supply are important. We use an ensemble of statistically downscaled CMIP5 General Circulation Model outputs for RCP4.5 and RCP8.5 to force a cryospheric-hydrological model and generate transient hydrological projections for the entire 21st century for the upper Indus basin. Three methodological advances are introduced: (i) A new precipitation dataset that corrects for the underestimation of high-altitude precipitation is used. (ii) The model is calibrated using data on river runoff, snow cover and geodetic glacier mass balance. (iii) An advanced statistical downscaling technique is used that accounts for changes in precipitation extremes. The analysis of the results focuses on changes in sources of runoff, seasonality and hydrological extremes. We conclude that the future of the upper Indus basin's water availability is highly uncertain in the…

Adolescent obesity and depression are increasingly prevalent and are currently recognised as major public health concerns worldwide. The aim of this study is to evaluate the bi-directional associations between obesity and depression in adolescents using longitudinal studies. A systematic literature search was conducted using Pubmed (including Medline), PsycINFO, Embase, CINAHL, BIOSIS Preview and the Cochrane Library databases. According to the inclusion criteria, 13 studies were found where seven studies evaluated depression leading to obesity and six other studies examined obesity leading to depression. Using a bias-adjusted quality effects model for the meta-analysis, we found that adolescents who were depressed had a 70% (RR 1.70, 95% CI: 1.40, 2.07) increased risk of being obese, conversely obese adolescents had an increased risk of 40% (RR 1.40, 95% CI: 1.16, 1.70) of being depressed. The risk difference (RD) of early adolescent depression leading to obesity is 3% higher risk than it is for obesity leading to depression. In sensitivity analysis, the association between…

OBJECTIVE: The aim of this study was to develop and validate a short form of the Eating Disorder Examination Questionnaire (EDE-Q) for routine, including session by session, outcome assessment. METHOD: The current, 28-item version (6.0) of the EDE-Q was completed by 489 individuals aged 18-72 with various eating disorders recruited from three UK specialist eating disorder services. Rasch analysis was carried out on factors identified by means of principal component analysis, which in combination with expert ratings informed the development of an EDE-Q short form. The shortened questionnaire's reliability, validity and sensitivity was assessed based on online data collected from students of a UK university and volunteers with a history of eating disorders recruited from a national eating disorders charity aged 18-74 (N = 559). RESULTS: A 12-item short form, the Eating Disorder Examination Questionnaire Short (EDE-QS) was derived. The new measure showed high internal consistency (Cronbach's α = .913) and temporal stability (ICC = .93; p < .001). It was highly correlated with the…

Remote polar and deepwater fish faunas are under pressure from ongoing climate change and increasing fishing effort. However, these fish communities are difficult to monitor for logistic and financial reasons. Currently, monitoring of marine fishes largely relies on invasive techniques such as bottom trawling, and on official reporting of global catches, which can be unreliable. Thus, there is need for alternative and non-invasive techniques for qualitative and quantitative oceanic fish surveys. Here we report environmental DNA (eDNA) metabarcoding of seawater samples from continental slope depths in Southwest Greenland. We collected seawater samples at depths of 188-918 m and compared seawater eDNA to catch data from trawling. We used Illumina sequencing of PCR products to demonstrate that eDNA reads show equivalence to fishing catch data obtained from trawling. Twenty-six families were found with both trawling and eDNA, while three families were found only with eDNA and two families were found only with trawling. Key commercial fish species for Greenland were the most abundant…

BACKGROUND: Fecal microbiota transplantation (FMT) is a microbiota-based therapy that shows therapeutic potential in recurrent or refractory Clostridium difficile infections and other intestinal or extra-intestinal disorders. Nonetheless, adverse events (AEs) remain a major challenge in the application of FMT. AIM: To review the AEs of FMT and to address the concerns of safety during the procedure. METHODS: Publications were retrieved in the databases of Medline, Embase and Cochrane Library. AEs were classified according to their causality with FMT or their severity. RESULTS: A total of 7562 original articles about FMT were identified in this study, 50 of them fulfilled the inclusion criteria. Totally 78 kinds of AEs were revealed enrolled in these 50 selected publications. The total incidence rate of AEs was 28.5%. Among the 42 publications, 5 kinds were definitely and 38 kinds were probably related to FMT. The commonest FMT-attributable AE was abdominal discomfort, which was reported in 19 publications. For upper gastrointestinal routes of FMT, 43.6% (89/204) patients were…

BACKGROUND: Prior studies have noted significant health disadvantages experienced by LGBT (lesbian, gay, bisexual, and transgender) populations in the US. While several studies have identified that fears or experiences of stigma and disclosure of sexual orientation and/or gender identity to health care providers are significant barriers to health care utilization for LGBT people, these studies have concentrated almost exclusively on urban samples. Little is known about the impact of stigma specifically for rural LGBT populations, who may have less access to quality, LGBT-sensitive care than LGBT people in urban centers. METHODOLOGY: LBGT individuals residing in rural areas of the United States were recruited online to participate in a survey examining the relationship between stigma, disclosure and "outness," and utilization of primary care services. Data were collected and analyzed regarding LGBT individuals' demographics, health care access, health risk factors, health status, outness to social contacts and primary care provider, and anticipated, internalized, and enacted stigmas.…

Autodock Vina is a very popular, and highly cited, open source docking program. Here we present a scoring function which we call Vinardo (Vina RaDii Optimized). Vinardo is based on Vina, and was trained through a novel approach, on state of the art datasets. We show that the traditional approach to train empirical scoring functions, using linear regression to optimize the correlation of predicted and experimental binding affinities, does not result in a function with optimal docking capabilities. On the other hand, a combination of scoring, minimization, and re-docking on carefully curated training datasets allowed us to develop a simplified scoring function with optimum docking performance. This article provides an overview of the development of the Vinardo scoring function, highlights its differences with Vina, and compares the performance of the two scoring functions in scoring, docking and virtual screening applications. Vinardo outperforms Vina in all tests performed, for all datasets analyzed. The Vinardo scoring function is available as an option within Smina, a fork of Vina,…

Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When…

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the…

BACKGROUND: Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. METHODS: We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. RESULTS: Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs.…

Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the…

Abiotic stresses such as drought, heat or salinity are a major cause of yield loss worldwide. Recent studies revealed that the acclimation of plants to a combination of different environmental stresses is unique and cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. Here we report on the response of Arabidopsis thaliana to a combination of salt and heat stress using transcriptome analysis, physiological measurements and mutants deficient in abscisic acid, salicylic acid, jasmonic acid or ethylene signaling. Arabidopsis plants were found to be more susceptible to a combination of salt and heat stress compared to each of the different stresses applied individually. The stress combination resulted in a higher ratio of Na+/K+ in leaves and caused the enhanced expression of 699 transcripts unique to the stress combination. Interestingly, many of the transcripts that specifically accumulated in plants in response to the salt and heat stress combination were associated with the plant hormone abscisic acid. In accordance…

OBJECTIVES: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis. METHODS: Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets. RESULTS: Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM…

BACKGROUND: There is a rapidly growing interest in psychological well-being (PWB) as outcome of interventions. Ryff developed theory-based indicators of PWB that are consistent with a eudaimonic perspective of happiness. Numerous interventions have been developed with the aim to increase PWB. However, the effects on PWB measured as coherent outcome have not been examined across studies yet. This meta-analysis of randomized controlled trials of behavioral interventions aims to answer the question whether it is possible to enhance PWB. METHODS: A systematic literature search was performed in PsycINFO, Cochrane and Web of Science. To be included, studies had to be randomized controlled trials of behavioral interventions with psychological well-being as primary or secondary outcome measure, measured with either Ryff's Psychological Well-Being Scales or the Mental Health Continuum-Short Form. The meta-analysis was performed using a random effects model. From the 2,298 articles found, 27 met the inclusion criteria. The included studies involved 3,579 participants. RESULTS: We found a…

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological…

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data. METHODS: This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH) and healthy controls (HC). Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4) and intestinal BA signalling, as well as IM composition were assessed. RESULTS: 53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA), chenodeoxycholic acid (CDCA) and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons).…

Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic…

The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception-women reported higher arousal when watching videos that induced sadness. The findings suggest…

Sustainable development efforts in urban areas often focus on understanding and managing factors that influence all aspects of health and wellbeing. Research has shown that public parks and green space provide a variety of physical, psychological, and social benefits to urban residents, but few studies have examined the influence of parks on comprehensive measures of subjective wellbeing at the city level. Using 2014 data from 44 U.S. cities, we evaluated the relationship between urban park quantity, quality, and accessibility and aggregate self-reported scores on the Gallup-Healthways Wellbeing Index (WBI), which considers five different domains of wellbeing (e.g., physical, community, social, financial, and purpose). In addition to park-related variables, our best-fitting OLS regression models selected using an information theory approach controlled for a variety of other typical geographic and socio-demographic correlates of wellbeing. Park quantity (measured as the percentage of city area covered by public parks) was among the strongest predictors of overall wellbeing, and the…

This study examined the influence of pyrolysis temperature on biochar characteristics and evaluated its suitability for carbon capture and energy production. Biochar was produced from corn stover using slow pyrolysis at 300, 400 and 500°C and 2 hrs holding time. The experimental biochars were characterized by elemental analysis, BET, FTIR, TGA/DTA, NMR (C-13). Higher heating value (HHV) of feedstock and biochars was measured using bomb calorimeter. Results show that carbon content of corn stover biochar increased from 45.5% to 64.5%, with increasing pyrolysis temperatures. A decrease in H:C and O:C ratios as well as volatile matter, coupled with increase in the concentration of aromatic carbon in the biochar as determined by FTIR and NMR (C-13) demonstrates a higher biochar carbon stability at 500°C. It was estimated that corn stover pyrolysed at 500°C could provide of 10.12 MJ/kg thermal energy. Pyrolysis is therefore a potential technology with its carbon-negative, energy positive and soil amendment benefits thus creating win- win scenario.

Backspliced circular RNAs (circRNAs) are prevalent in many eukaryotic systems and are spliced from thousands of different genes. Where examined, circRNAs are often highly stable and the mechanisms by which cells degrade and/or clear circRNAs from the cells are unknown. Here we investigated the possibility that cells can eliminate circRNAs into extracellular space, possibly within released vesicles such as exosomes and microvesicles. From three different cell lines and examining multiple circRNAs, we show that extracellular vesicle (EVs) preparations recovered from cell culture conditioned media contain established circRNAs. Moreover, these circRNAs are enriched over their linear counterparts within EV preparations when compared to the producing cells. This supports the idea that expulsion from cells into extracellular space, as by EVs release, can be a mechanism by which cells clear circRNAs. Moreover, since EVs can be taken up by other cells, excreted circRNAs could contribute to cell to cell communication.

We summarized the recently published, peer-reviewed literature that examined the impact of investments in social services or investments in integrated models of health care and social services on health outcomes and health care spending. Of 39 articles that met criteria for inclusion in the review, 32 (82%) reported some significant positive effects on either health outcomes (N = 20), health care costs (N = 5), or both (N = 7). Of the remaining 7 (18%) studies, 3 had non-significant results, 2 had mixed results, and 2 had negative results in which the interventions were associated with poorer health outcomes. Our analysis of the literature indicates that several interventions in the areas of housing, income support, nutrition support, and care coordination and community outreach have had positive impact in terms of health improvements or health care spending reductions. These interventions may be of interest to health care policymakers and practitioners seeking to leverage social services to improve health or reduce costs. Further testing of models that achieve better outcomes at…

Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale-originally designed to assess a positive response bias-are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ's MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ's discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores…

Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size…

Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This…

Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary…

INTRODUCTION: Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section) and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge. METHODS: For this cohort study, we developed a survey on quality of analgesia following hospital…

AIMS: We investigated whether sprint interval training (SIT) was a time-efficient exercise strategy to improve insulin sensitivity and other indices of cardiometabolic health to the same extent as traditional moderate-intensity continuous training (MICT). SIT involved 1 minute of intense exercise within a 10-minute time commitment, whereas MICT involved 50 minutes of continuous exercise per session. METHODS: Sedentary men (27±8y; BMI = 26±6kg/m2) performed three weekly sessions of SIT (n = 9) or MICT (n = 10) for 12 weeks or served as non-training controls (n = 6). SIT involved 3x20-second 'all-out' cycle sprints (~500W) interspersed with 2 minutes of cycling at 50W, whereas MICT involved 45 minutes of continuous cycling at ~70% maximal heart rate (~110W). Both protocols involved a 2-minute warm-up and 3-minute cool-down at 50W. RESULTS: Peak oxygen uptake increased after training by 19% in both groups (SIT: 32±7 to 38±8; MICT: 34±6 to 40±8ml/kg/min; p<0.001 for both). Insulin sensitivity index (CSI), determined by intravenous glucose tolerance tests performed before and 72 hours…

Natural habitats have the ability to protect coastal communities against the impacts of waves and storms, yet it is unclear how different habitats complement each other to reduce those impacts. Here, we investigate the individual and combined coastal protection services supplied by live corals on reefs, seagrass meadows, and mangrove forests during both non-storm and storm conditions, and under present and future sea-level conditions. Using idealized profiles of fringing and barrier reefs, we quantify the services supplied by these habitats using various metrics of inundation and erosion. We find that, together, live corals, seagrasses, and mangroves supply more protection services than any individual habitat or any combination of two habitats. Specifically, we find that, while mangroves are the most effective at protecting the coast under non-storm and storm conditions, live corals and seagrasses also moderate the impact of waves and storms, thereby further reducing the vulnerability of coastal regions. Also, in addition to structural differences, the amount of service supplied by…

BACKGROUND: A wide range of screening tools are available to detect common mental disorders (CMDs), but few have been specifically developed for populations in low and middle income countries (LMIC). Cross-cultural application of a screening tool requires that its validity be assessed against a gold standard diagnostic interview. Validation studies of brief CMD screening tools have been conducted in several LMIC, but until now there has been no review of screening tools for all CMDs across all LMIC populations. METHODS: A systematic review with broad inclusion criteria was conducted, producing a comprehensive summary of brief CMD screening tools validated for use in LMIC populations. For each validation, the diagnostic odds ratio (DOR) was calculated as an easily comparable measure of screening tool validity. Average DOR results weighted by sample size were calculated for each screening tool, enabling us to make broad recommendations about best performing screening tools. RESULTS: 153 studies fulfilled our inclusion criteria. Because many studies validated two or more screening…

BACKGROUND: Establishing which upper limb outcome measures are most commonly used in stroke studies may help in improving consensus among scientists and clinicians. OBJECTIVE: In this study we aimed to identify the most commonly used upper limb outcome measures in intervention studies after stroke and to describe domains covered according to ICF, how measures are combined, and how their use varies geographically and over time. METHODS: Pubmed, CinHAL, and PeDRO databases were searched for upper limb intervention studies in stroke according to PRISMA guidelines and477 studies were included. RESULTS: In studies 48different outcome measures were found. Only 15 of these outcome measures were used in more than 5% of the studies. The Fugl-Meyer Test (FMT)was the most commonly used measure (in 36% of studies). Commonly used measures covered ICF domains of body function and activity to varying extents. Most studies (72%) combined multiple outcome measures: the FMT was often combined with the Motor Activity Log (MAL), the Wolf Motor Function Test and the Action Research Arm Test, but…

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many 'pollinator-friendly' seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and…

The substantial gender gap in the science, technology, engineering, and mathematics (STEM) workforce can be traced back to the underrepresentation of women at various milestones in the career pathway. Calculus is a necessary step in this pathway and has been shown to often dissuade people from pursuing STEM fields. We examine the characteristics of students who begin college interested in STEM and either persist or switch out of the calculus sequence after taking Calculus I, and hence either continue to pursue a STEM major or are dissuaded from STEM disciplines. The data come from a unique, national survey focused on mainstream college calculus. Our analyses show that, while controlling for academic preparedness, career intentions, and instruction, the odds of a woman being dissuaded from continuing in calculus is 1.5 times greater than that for a man. Furthermore, women report they do not understand the course material well enough to continue significantly more often than men. When comparing women and men with above-average mathematical abilities and preparedness, we find women…

From the foods we eat and the houses we construct, to our religious practices and political organization, to who we can marry and the types of games we teach our children, the diversity of cultural practices in the world is astounding. Yet, our ability to visualize and understand this diversity is limited by the ways it has been documented and shared: on a culture-by-culture basis, in locally-told stories or difficult-to-access repositories. In this paper we introduce D-PLACE, the Database of Places, Language, Culture, and Environment. This expandable and open-access database (accessible at https://d-place.org) brings together a dispersed corpus of information on the geography, language, culture, and environment of over 1400 human societies. We aim to enable researchers to investigate the extent to which patterns in cultural diversity are shaped by different forces, including shared history, demographics, migration/diffusion, cultural innovations, and environmental and ecological conditions. We detail how D-PLACE helps to overcome four common barriers to understanding these forces:…