Find research datasets worth reusing

opencc-zeroDec 2010View details →

Data from: Random sperm use and genetic effects on worker caste fate in Atta colombica leaf-cutting ants

Sperm competition can produce fascinating adaptations with far-reaching evolutionary consequences. Social taxa make particularly interesting models, because the outcome of sexual selection determines the genetic composition of groups, with attendant sociobiological consequences. Here, we use molecular tools to uncover some of the mechanisms and consequences of sperm competition in the leaf-cutting ant Atta colombica, a species with extreme worker size polymorphism. Competitive PCR allowed quantification of the relative numbers of sperm stored by queens from different males, and offspring genotyping revealed how sperm number translated into paternity of eggs and adult workers. We demonstrate that fertilisation success is directly related to sperm numbers, that stored sperm are well mixed and that egg paternity is constant over time. Moreover, worker size was found to have a considerable genetic component, despite expectations that genetic effects on caste fate should be reduced in species with a low degree of polyandry. Our data suggest that sexual conflict over paternity is largely resolved by the lifetime commitment between mates generated by long-term sperm storage, and show that genetic variation for caste can persist in societies with comparatively high relatedness.

Data from: Phage display peptide libraries: deviations from randomness and correctives

Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library. In a previous study we implemented Next Generation Sequencing to evaluate a naïve library and discovered severe deviations from randomness in UAG codon overrepresentation as well as in high G phosphoramidite abundance causing amino acid distribution biases. In this study we demonstrate that the UAG overrepresentation can be attributed to the burden imposed on the phage upon the assembly of the recombinant Protein 8 subunits. This was corrected by constructing the libraries using supE44-containing bacteria which suppress the UAG driven abortive termination. We also demonstrate that the overabundance of G stems from variant synthesis-efficiency and can be corrected using compensating oligonucleotide-mixtures calibrated by Mass Spectroscopy. Construction of libraries implementing these correctives results in markedly improved libraries that display random distribution of amino acids, thus ensuring that enriched peptides obtained in biopanning represent a genuine selection event, a fundamental assumption for phage display applications.

opencc-zeroDec 2015View details →

Data from: Early sitting in ischemic stroke patients (SEVEL): a randomized controlled trial

Background: Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients. Objective: As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome. Methods: This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0–2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure. Results: One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0–2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms. Conclusion: Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke outcome with a realized 37% power. However, enrollment was sufficient to rule out effect sizes greater than 25% with 80% power, indicating that early sitting is unlikely to have an extreme effect in either direction on stroke outcome. Additionally, we were not able to provide a blinded assessment of the primary outcome. Taking these limitations into account, our results may help guide the development of more effective acute stroke rehabilitation strategies, and the design of future acute stroke trials involving out of bed activities and other mobilization regimens.

opencc-zeroDec 2014View details →

Data from: Sexual selection has minimal impact on effective population sizes in species with high rates of random offspring mortality: an empirical demonstration using fitness distributions

The effective population size (Ne) is a fundamental parameter in population genetics that influences the rate of loss of genetic diversity. Sexual selection has the potential to reduce Ne by causing the sex-specific distributions of individuals that successfully reproduce to diverge. To empirically estimate the effect of sexual selection on Ne, we obtained fitness distributions for males and females from an outbred, laboratory-adapted population of Drosophila melanogaster. We observed strong sexual selection in this population (the variance in male reproductive success was ∼14 times higher than that for females), but found that sexual selection had only a modest effect on Ne, which was 75% of the census size. This occurs because the substantial random offspring mortality in this population diminishes the effects of sexual selection on Ne, a result that necessarily applies to other high fecundity species. The inclusion of this random offspring mortality creates a scaling effect that reduces the variance/mean ratios for male and female reproductive success and causes them to converge. Our results demonstrate that measuring reproductive success without considering offspring mortality can underestimate Ne and overestimate the genetic consequences of sexual selection. Similarly, comparing genetic diversity among different genomic components may fail to detect strong sexual selection.

opencc-zeroDec 2018View details →

Data from: Relative effects of LDL-C on ischaemic stroke & coronary disease: a Mendelian randomization study

Objective: To examine the causal relevance of lifelong differences in LDL-C for ischaemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. Methods: We undertook a two-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. Results: A 1 mmol/L higher genetically-determined LDL-C was associated with a 50% higher risk of CHD (OR: 1.49, 95%CI: 1.32-1.68, p=1.1x10-8). By contrast, the causal effect of LDL-C was much weaker for IS (OR: 1.12, 95%CI: 0.96-1.30, p=0.14; p for heterogeneity=2.6x10-3) and, in particular, for cardioembolic stroke (OR: 1.06, 95%CI: 0.84-1.33, p=0.64; p for heterogeneity=8.6x10-3) when compared with that for CHD. Conclusions: In contrast with the consistent effects of LDL-C lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of aetiologically distinct IS subtypes may contribute to the differences observed.

Data from: Female-biased dispersal and non-random gene flow of MC1R variants do not result in a migration load in barn owls

Non-random gene flow is a widely neglected force in evolution and ecology. This genotype-dependent dispersal is difficult to assess, yet can impact the genetic variation of natural populations and their fitness. In this work, we demonstrate a high immigration rate of barn owls (Tyto alba) inside a Swiss population surveyed during 15 years. Using 10 microsatellite loci as an indirect method to characterize dispersal, two third of the genetic tests failed to detect a female-biased dispersal, and Monte-Carlo simulations confirmed a low statistical power to detect sex-biased dispersal in case of high dispersal rate of both sexes. The capture-recapture data revealed a female-biased dispersal associated with an excess of heterozygote for the melanocortin-1 receptor gene (MC1R), which is responsible for their ventral rufous coloration. Thus, female homozygotes for the MC1R_white allele might be negatively selected during dispersal. Despite the higher immigration of females that are heterozygote at MC1R, non-random gene flow should not lead to a migration load regarding this gene because we did not detect an effect of MC1R on survival and reproductive success in our local population. The present study highlights the usefulness of using multiple methods to correctly decrypt dispersal and gene flow. Moreover, despite theoretical expectations, we show that non-random dispersal of particular genotypes does not necessarily lead to migration load in recipient populations.

Data from: Lasmiditan is an effective acute treatment for migraine A phase 3 randomized study

Objective: To assess the efficacy and safety of lasmiditan in the acute treatment of migraine. Methods: Adult patients with migraine were randomized (1:1:1) to a double-blind dose of oral lasmiditan 200 mg, lasmiditan 100 mg, or placebo, and were asked to treat their next migraine attack within 4 hours of onset. Over 48 hours following dosing, patients used an electronic diary to record headache pain, and also the presence of nausea, phonophobia, and photophobia, one of which was designated their most bothersome symptom (MBS). Results: Of the 1,856 patients who treated an attack, 77.9% had ≥1 cardiovascular risk factor in addition to migraine. Compared with placebo, more patients dosed with lasmiditan 200 mg were free from headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [95% confidence interval]: 2.6 [2.0, 3.6]; p<0.001); and similarly for lasmiditan 100 mg (28.2%; 2.2 [1.6, 3.0]; p<0.001). Furthermore, compared with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; 1.6 [1.3, 2.1]; p<0.001), and lasmiditan 100 mg (40.9%; 1.7 [1.3, 2.2]; p<0.001), were free from their MBS at 2 hours after dosing. Adverse events were mostly mild or moderate in intensity. Conclusions: Lasmiditan, dosed at 200 mg and 100 mg, was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.

opencc-zeroDec 2018View details →

Data from: Community disassembly and disease: realistic – but not randomized – biodiversity losses enhance parasite transmission

Debates over the relationship between biodiversity and disease dynamics underscore the need for a more mechanistic understanding of how changes in host community composition influence parasite transmission. Focusing on interactions between larval amphibians and trematode parasites, we experimentally contrasted the effects of host richness and species composition to identify the individual and joint contributions of both parameters on the infection levels of three trematode species. By combining experimental approaches with field surveys from 147 ponds, we further evaluated how richness effects differed between randomized and realistic patterns of species loss (i.e., community disassembly). Our results indicated that community-level changes in infection levels were due to host species composition, rather than richness. However, when composition patterns mirrored empirical observations along a natural assembly gradient, each added host species reduced infection success by 12 to 55%. No such effects occurred when assemblages were randomized. Mechanistically, these patterns were due to non-random host species assembly/disassembly: while highly competent species predominated in low diversity systems, less susceptible hosts became progressively more common as richness increased. These findings highlight the potential for combining information on host traits and assembly patterns to forecast diversity-mediated changes in multi-host disease systems.

Data from: Multilevel and quasi-Monte Carlo methods for uncertainty quantification in particle travel times through random heterogeneous porous media

In this study, we apply four Monte Carlo simulation methods, namely, Monte Carlo, quasi-Monte Carlo, multilevel Monte Carlo and multilevel quasi-Monte Carlo to the problem of uncertainty quantification in the estimation of the average travel time during the transport of particles through random heterogeneous porous media. We apply the four methodologies to a model problem where the only input parameter, the hydraulic conductivity, is modelled as a log-Gaussian random field by using direct Karhunen–Loéve decompositions. The random terms in such expansions represent the coefficients in the equations. Numerical calculations demonstrating the effectiveness of each of the methods are presented. A comparison of the computational cost incurred by each of the methods for three different tolerances is provided. The accuracy of the approaches is quantified via the mean square error.

opencc-zeroJul 2019View details →

Data from: The effect of promoting current local research activities on large monitors on the population's interest in health-related research – a randomized controlled trial

OBJECTIVE: The objectives of this study were threefold: to estimate people's interest in health-related research, to understand to what extent people appreciate being actively informed about current local health-related research and to investigate whether their interest can be influenced by advertising local current health-related research using large TV monitors. DESIGN: Randomized controlled trial using a stepped wedge design. SETTING: The emergency department waiting room at two public hospitals in northern Queensland, Australia. PARTICIPANTS: Waiting patients and their accompanying friends and relatives in the emergency department waiting room not requiring immediate medical attention. INTERVENTIONS: A TV monitor advertising local current health-related research. MAIN OUTCOME MEASURES: Odds ratio for the effect of intervention on changing the interest in health-related research compared to a control group while adjusting for gender, age and socioeconomic standard. RESULTS: The intervention significantly increased the short-term interest in health-related research with an odds ratio of 1.3 (1.1-1.7, p=0.0063). We also noted that being female and being older was correlated to a higher interest in health-related research CONCLUSIONS: This study found that proactive information significantly increased the general populations' interest in health-related research. There are reasonable set up costs involved but the costs for maintaining the system were very low. Hence, it seems reasonable that research-active organizations should give much higher priority to this type of activity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) with the registration number ACTRN12617001085369

Data from: Reducing therapeutic misconception: a randomized intervention trial in hypothetical clinical trials

Background: Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials. Methods: This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control) in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range=10-50), and willingness to participate in the clinical trial. Results: 154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female); 74 (48.1%) had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p=0.004) in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p=0.017). Willingness to participate in the hypothetical trial was not significantly different (p=0.603) between intervention (52.1%, 95% CI [40.2 to 62.4]) and control (56.3%, 95% CI [45.3 to 66.6] groups. Conclusions: An enhanced educational intervention augmenting traditional informed consent led to a meaningful reduction in therapeutic misconception without a statistically significant change in willingness to enroll in hypothetical clinical trials. Additional study of this intervention is required in real-world clinical trials.

opencc-zeroDec 2018View details →

Data from: Are multiple views superior to a single view when teaching hip surgery? a single-blinded randomized controlled trial of technical skill acquisition

Purpose: Surgical education videos currently all use a single point of view (POV) with the trainee locked onto a fixed viewpoint, which may not deliver sufficient information for complex procedures. We developed a novel multiple POV video system and evaluated its training outcome compared with traditional single POV. Methods: We filmed a hip resurfacing procedure performed by an expert attending using 8 cameras in theatre. 30 medical students were randomly and equally allocated to learn the procedure using the multiple POV (experiment group [EG]) versus single POV system (control group [CG]). Participants advanced a pin into the femoral head as demonstrated in the video. We measured the drilling trajectories and compared it with pre-operative plan to evaluate distance of the pin insertion and angular deviations. Two orthopedic attendings expertly evaluated the participants' performance using a modified global rating scale (GRS). There was a pre-video knowledge test that was repeated post-simulation alongside a Likert-scale questionnaire. Results: The angular deviation of the pin in EG was significantly less by 29% compared to CG (p=0.037), with no significant difference in the entry point's distance between groups (p=0.204). The GRS scores for EG were higher than CG (p=0.046). There was a 32% higher overall knowledge test score (p<0.001) and 21% improved Likert-scale questionnaire score (p=0.002) after video-learning in EG than CG, albeit no significant difference in the knowledge test score before video-learning (p=0.721). Conclusion: The novel multiple POV provided significant objective and subjective advantages over single POV for acquisition of technical skills in hip surgery.

Data from: Random sequences are an abundant source of bioactive RNAs or peptides

It is generally assumed that new genes arise through duplication and/or recombination of existing genes. The probability that a new functional gene could arise out of random non-coding DNA is so far considered to be negligible, as it seems unlikely that such an RNA or protein sequence could have an initial function that influences the fitness of an organism. Here, we have tested this question systematically, by expressing clones with random sequences in Escherichia coli and subjecting them to competitive growth. Contrary to expectations, we find that random sequences with bioactivity are not rare. In our experiments we find that up to 25% of the evaluated clones enhance the growth rate of their cells and up to 52% inhibit growth. Testing of individual clones in competition assays confirms their activity and provides an indication that their activity could be exerted by either the transcribed RNA or the translated peptide. This suggests that transcribed and translated random parts of the genome could indeed have a high potential to become functional. The results also suggest that random sequences may become an effective new source of molecules for studying cellular functions, as well as for pharmacological activity screening.

opencc-zeroDec 2013View details →

Data from: Assessment of the quality of reporting in randomized controlled trials of acupuncture in the Korean literature using the CONSORT statement and the STRICTA guidelines

Objectives: This study aimed to assess the completeness of reporting of RCTs of acupuncture in the Korean literature. Design: Systematic review. Methods: We searched 12 Korean databases and 7 Korean journals to identify eligible RCTs of acupuncture published from 1996 to July 2011. We used the Consolidated Standards of Reporting Trials (CONSORT) checklist for parallel RCTs and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) to assess the quality of reporting in Korean RCTs. We compared the completeness of reporting of CONSORT and STRICTA items in RCTs published in two time periods (1996-2004 referred to as the early period and 2005-2011 referred to as the late period). Results: We analysed 146 eligible RCTs using the CONSORT statement concerning RCTs of both needling and non-needling acupuncture and the STRICTA guidelines for 90 trials of needling acupuncture. Among the 103 RCTs in the late period, the proportion of RCTs that completely reported the CONSORT items of outcome definition (15.5%), sample size calculation (2.9%), randomisation (56%), allocation concealment (5.8%), implementation of allocation (11.7%), outcome assessor blinding (20.3%), flow of participants (25.2%), number of participants analysed (19.4%), ancillary analyses (0.0%), adverse events (24.3%), generalisability of findings (1.9%) and overall evidence (32.0%) remained small. Among the 61 RCTs of needling acupuncture in the late period, the STRICTA items of setting/context (24.6%) and practitioner background (27.9%) showed incomplete reporting. The completeness of reporting improved over time in several CONSORT and STRICTA items. Conclusion: The completeness of reporting of Korean RCTs of acupuncture was suboptimal according to the CONSORT and revised STRICTA statements. Trial authors and journal editors should use the CONSORT statement and the STRICTA guidelines for transparent reporting in Korean RCTs of acupuncture. The endorsement of the CONSORT and revised STRICTA statements in author instructions is also required.

Data from: Sialendoscopy enhances salivary gland function in Sjögren's syndrome: a 6 month follow-up, randomized and controlled, single blind study

Objectives: To assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren's syndrome (SS). Methods: Forty nine SS patients were randomly assigned to a control group (n=15) and two intervention groups: irrigation of the major glands with saline (n=16) or with saline followed by triamcinolone acetonide (TA) in saline (n=18). Unstimulated whole saliva flow (UWS), chewing stimulated whole saliva flow (SWS), citric-acid stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory score (XI), and EULAR SS Patient Reported Index (ESSPRI) were obtained 1 week (T0) before, and 1(T1), 8(T8), 16(T16), and 24(T24) weeks after sialendoscopy. Results: Median baseline UWS, SWS and SPF scores were, respectively, 0.14, 0.46, and 0.22mL/min. After intervention, significant increases in UWS and SWS were observed in the saline group (at T8 (p=0.013) and T24 (p=0.004)) and the saline/TA group (at T24 (p=0.03) and T=16 (p=0.035). SPF was increased significantly in the saline/TA group at T24 (p=0.03). XI scores declined after sialendoscopy in both intervention groups. Compared to the control group, CODS, XI, and ESSPRI improved in the intervention groups. UWS, SWS, and SPF were higher in the intervention groups compared to the control group, but these differences were not significant except for SPF in the saline/TA group at T24 (p=0.005). Conclusions: Irrigation of the major salivary glands in SS patients enhances salivary flow and reduces xerostomia up to 6 months after sialendoscopy.

Data from: Costs and benefits of non-random seed release for long distance dispersal in wind-dispersed plant species

The dispersal ability of plants is a major factor driving ecological responses to global change. In wind-dispersed plant species, non-random seed release in relation to wind speeds has been identified as a major determinant of dispersal distances. However, little information is available about the costs and benefits of non-random abscission and the consequences of timing for dispersal distances. We asked: 1) To what extent is non-random abscission able to promote long-distance dispersal and what is the effect of potentially increased pre-dispersal risk costs? 2) Which meteorological factors and respective timescales are important for maximizing dispersal? These questions were addressed by combining a mechanistic modelling approach and field data collection for herbaceous wind-dispersed species. Model optimization with a dynamic dispersal approach using measured hourly wind speed showed that plants can increase long-distance dispersal by developing a hard wind speed threshold below which no seeds are released. At the same time, increased risk costs limit the possibilities for dispersal distance gain and reduce the optimum level of the wind speed threshold, in our case (under representative Dutch meteorological conditions) to a threshold of 5-6 m s-1. The frequency and predictability (auto-correlation in time) of pre-dispersal seed-loss had a major impact on optimal non-random abscission functions and resulting dispersal distances. We observed a similar, but more gradual, bias towards higher wind speeds in six out of seven wind-dispersed species under natural conditions. This confirmed that non-random abscission exists in many species and that, under local Dutch meteorological conditions, abscission was biased towards winds exceeding 5-6 m s-1. We conclude that timing of seed release can vastly enhance dispersal distances in wind-dispersed species, but increased risk costs may greatly limit the benefits of selecting wind conditions for long-distance dispersal, leading to moderate seed abscission thresholds, depending on local meteorological conditions and disturbances.

opencc-zeroDec 2015View details →

Data from: Effects of cell-cycle-dependent expression on random fluctuations in protein levels

Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyse a model where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulae quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulae reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate the existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division, minimizes noise from bursty expression for a fixed mean protein level. By contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of the cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.

Data from: Childhood adiposity and type 1 diabetes: a Mendelian randomization study

BACKGROUND: The incidence of type 1 diabetes (T1D) is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations. METHODS AND FINDINGS: We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood adiposity in children aged 2-10 years. Summary-level association results for these 23 SNPs with childhood-onset (<17 years) T1D were extracted from a meta-analysis of genome-wide association study with 5,913 T1D cases and 8,828 reference samples. Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1.64 per standard deviation score in body mass index [SDS-BMI]). A sensitivity analysis provided evidence of horizontal pleiotropy bias (p = 0.04) diluting the estimates towards the null. We therefore applied Egger regression and multivariable Mendelian randomization methods to control for this type of bias and found evidence in support of a role of childhood adiposity in T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44). Limitations of our study include that underlying genes and their mechanisms for most of the genetic variants included in the score are not known. Mendelian randomization requires large sample sizes, and power was limited to provide precise estimates. This research has been conducted using data from the Early Growth Genetics (EGG) Consortium, the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, the Tobacco and Genetics (TAG) Consortium, and the Social Science Genetic Association Consortium (SSGAC), as well as meta-analysis results from a T1D genome-wide association study. CONCLUSIONS: This study provides genetic support for a link between childhood adiposity and T1D risk. Together with evidence from observational studies, our findings further emphasize the importance of measures to reduce the global epidemic of childhood obesity and encourage mechanistic studies.

Data from: A practical introduction to random forest for genetic association studies in ecology and evolution

Large genomic studies are becoming increasingly common with advances in sequencing technology, and our ability to understand how genomic variation influences phenotypic variation between individuals has never been greater. The exploration of such relationships first requires the identification of associations between molecular markers and phenotypes. Here we explore the use of Random Forest (RF), a powerful machine learning algorithm, in genomic studies to discern loci underlying both discrete and quantitative traits, particularly when studying wild or non-model organisms. RF is becoming increasingly used in ecological and population genetics because, unlike traditional methods, it can efficiently analyze thousands of loci simultaneously and account for non-additive interactions. However, understanding both the power and limitations of Random Forest is important for its proper implementation and the interpretation of results. We therefore provide a practical introduction to the algorithm and its use for identifying associations between molecular markers and phenotypes, discussing such topics as data limitations, algorithm initiation and optimization, as well as interpretation. We also provide short R tutorials as examples, with the aim of providing a guide to the implementation of the algorithm. Topics discussed here are intended to serve as an entry point for molecular ecologists interested in employing Random Forest to identify trait associations in genomic data sets.

Data from: Ginkgo biloba extract for prevention of acute mountain sickness: a systematic review and meta-analysis of randomized controlled trials

Study objective: Trials of ginkgo biloba extract (GBE) for the prevention of acute mountain sickness (AMS) have been published since 1996. Because of their conflicting results, the efficacy of GBE remains unclear. We performed a systematic review and meta-analysis to assess whether GBE prevents acute mountain sickness. Methods: The Cochrane Library, EMBASE, Google Scholar, and PubMed databases were searched for articles published up to May 20, 2017. Only randomized controlled trials were included. AMS defined as acute mountain sickness–cerebral(AMS-C) score≧0.7 or Lake Louise Score (LLS)≧3 with headache. The main outcome measures were the relative risks of AMS in participants receiving GBE for prophylaxis. Meta-analyses were conducted using random-effects models. Sensitivity analyses, subgroup analyses and tests for publication bias were conducted. Results: Six published articles with a total of 451 participants met all eligibility criteria. In the primary meta-analysis of all 7 study groups, GBE showed trend of AMS prophylaxis, but it is not statistically significant (RR =0.68; 95% CI: 0.45 to 1.04; p-value=0.08) (Figure 2). The I2 statistic was 58.7% (p-value=0.02), indicating substantial heterogeneity. The results of subgroup analyses of studies with low risk of bias, low starting altitude (<2500 m), number of treatment days before ascending and dosage of GBE were similar. Conclusions: The currently available data suggest that although GBE may tend toward AMS prophylaxis, there are not enough data to show the statistically significant effect of GBE for preventing AMS. Further large randomized control studies are warranted.