Assessment of regression-based methods to adjust for publication bias through a comprehensive simulation study

<p>Abstract</p> <p>Background</p> <p>In meta-analysis, the presence of funnel plot asymmetry is attributed to publication or other small-study effects, which causes larger effects to be observed in the smaller studies. This issue potentially mean inappropriate conclusions are drawn from a meta-analysis. If meta-analysis is to be used to inform decision-making, a reliable way to adjust pooled estimates for potential funnel plot asymmetry is required.</p> <p>Methods</p> <p>A comprehensive simulation study is presented to assess the performance of different adjustment methods including the novel application of several regression-based methods (which are commonly applied to detect publication bias rather than adjust for it) and the popular Trim & Fill algorithm. Meta-analyses with binary outcomes, analysed on the log odds ratio scale, were simulated by considering scenarios with and without i) publication bias and; ii) heterogeneity. Publication bias was induced through two underlying mechanisms assuming the probability of publication depends on i) the study effect size; or ii) the p-value.</p> <p>Results</p> <p>The performance of all methods tended to worsen as unexplained heterogeneity increased and the number of studies in the meta-analysis decreased. Applying the methods conditional on an initial test for the presence of funnel plot asymmetry generally provided poorer performance than the unconditional use of the adjustment method. Several of the regression based methods consistently outperformed the Trim & Fill estimators.</p> <p>Conclusion</p> <p>Regression-based adjustments for publication bias and other small study effects are easy to conduct and outperformed more established methods over a wide range of simulation scenarios.</p

The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: A simulation study

<p>Abstract</p> <p>Background</p> <p>Meta-analysis of continuous outcomes traditionally uses mean difference (MD) or standardized mean difference (SMD; mean difference in pooled standard deviation (SD) units). We recently used an alternative ratio of mean values (RoM) method, calculating RoM for each study and estimating its variance by the delta method. SMD and RoM allow pooling of outcomes expressed in different units and comparisons of effect sizes across interventions, but RoM interpretation does not require knowledge of the pooled SD, a quantity generally unknown to clinicians.</p> <p>Objectives and methods</p> <p>To evaluate performance characteristics of MD, SMD and RoM using simulated data sets and representative parameters.</p> <p>Results</p> <p>MD was relatively bias-free. SMD exhibited bias (~5%) towards no effect in scenarios with few patients per trial (n = 10). RoM was bias-free except for some scenarios with broad distributions (SD 70% of mean value) and medium-to-large effect sizes (0.5–0.8 pooled SD units), for which bias ranged from -4 to 2% (negative sign denotes bias towards no effect). Coverage was as expected for all effect measures in all scenarios with minimal bias. RoM scenarios with bias towards no effect exceeding 1.5% demonstrated lower coverage of the 95% confidence interval than MD (89–92% vs. 92–94%). Statistical power was similar. Compared to MD, simulated heterogeneity estimates for SMD and RoM were lower in scenarios with bias because of decreased weighting of extreme values. Otherwise, heterogeneity was similar among methods.</p> <p>Conclusion</p> <p>Simulation suggests that RoM exhibits comparable performance characteristics to MD and SMD. Favourable statistical properties and potentially simplified clinical interpretation justify the ratio of means method as an option for pooling continuous outcomes.</p

Quantifying Selective Reporting and the Proteus Phenomenon for Multiple Datasets with Similar Bias

Meta-analyses play an important role in synthesizing evidence from diverse studies and datasets that address similar questions. A major obstacle for meta-analyses arises from biases in reporting. In particular, it is speculated that findings which do not achieve formal statistical significance are less likely reported than statistically significant findings. Moreover, the patterns of bias can be complex and may also depend on the timing of the research results and their relationship with previously published work. In this paper, we present an approach that is specifically designed to analyze large-scale datasets on published results. Such datasets are currently emerging in diverse research fields, particularly in molecular medicine. We use our approach to investigate a dataset on Alzheimer's disease (AD) that covers 1167 results from case-control studies on 102 genetic markers. We observe that initial studies on a genetic marker tend to be substantially more biased than subsequent replications. The chances for initial, statistically non-significant results to be published are estimated to be about 44% (95% CI, 32% to 63%) relative to statistically significant results, while statistically non-significant replications have almost the same chance to be published as statistically significant replications (84%; 95% CI, 66% to 107%). Early replications tend to be biased against initial findings, an observation previously termed Proteus phenomenon: The chances for non-significant studies going in the same direction as the initial result are estimated to be lower than the chances for non-significant studies opposing the initial result (73%; 95% CI, 55% to 96%). Such dynamic patters in bias are difficult to capture by conventional methods, where typically simple publication bias is assumed to operate. Our approach captures and corrects for complex dynamic patterns of bias, and thereby helps generating conclusions from published results that are more robust against the presence of different coexisting types of selective reporting

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Information storing by biomagnetites

Since the discovery of the presence of biogenic magnetites in living organisms, there have been speculations on the role that these biomagnetites play in cellular processes. It seems that the formation of biomagnetite crystals is a universal phenomenon and not an exception in living cells. Many experimental facts show that features of organic and inorganic processes could be indistinguishable at nanoscale levels. Living cells are quantum "devices" rather than simple electronic devices utilizing only the charge of conduction electrons. In our opinion, due to their unusual biophysical properties, special biomagnetites must have a biological function in living cells in general and in the brain in particular. In this paper we advance a hypothesis that while biomagnetites are developed jointly with organic molecules and cellular electromagnetic fields in cells, they can record information about the Earth's magnetic vector potential of the entire flight in migratory birds.Comment: 17 pages, 3 figure

The relationship between the symptoms of female gonococcal infections and serum progesterone level and the genotypes of Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) in Wuhan, China

The objective of this investigation was to study the relationship between the symptoms of female gonococcal infections and serum progesterone level and the genotypes of Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) in Wuhan, China. Eighty-one strains of N. gonorrhoeae were harvested from the vaginal discharge of 975 adult females in Wuhan and were genotyped by using NG-MAST. Serum progesterone (P) and estradiol (E2) levels were measured by radio immunoassay (RIA) in 39 gonorrhea-infected patients with slight symptoms (asymptomatic group) and 42 patients with conspicuous symptoms (symptomatic group). The average levels of serum progesterone in the asymptomatic group were significantly higher than in the symptomatic group (p < 0.05), while no significant difference was found in serum estradiol between the two groups. Of 81 wild-type isolates, 50 NG-MAST sequence types were associated with female infections in Wuhan, and N. gonorrhoeae ST2951, ST735, and ST436 were principally found in asymptomatic patients. ST809 and ST369, however, were mainly detected in asymptomatic female subjects. Gonococcal genetic island (GGI)-positive and GGI-negative strains were found in both the asymptomatic group and the symptomatic group. In females with gonococcal infection, high serum progesterone level is associated with the absence of symptoms, but no association was revealed between genotypes and the presence of symptoms. The GGI bears no relation to the absence of symptoms in the patients

Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-Eukaryotes from a suspected homicide to estimate the post-mortem interval

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for longer periods. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones, soil chemical characteristics, mites and nematodes (by microscopy) and micro-Eukaryotes (by Illumina high throughput sequencing). We analysed soil samples collected beneath the remains of the head, upper and lower body and “control” samples taken a few meters away. The PMI estimated on hair 14C-data via bomb peak radiocarbon dating gave a time range of 1 to 2 years before the finding of the remains on site. Cluster analyses for chemical constituents, nematodes, mites and micro- Eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was likely to have been brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-Eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools

Wolbachia Infections Are Virulent and Inhibit the Human Malaria Parasite Plasmodium Falciparum in Anopheles Gambiae

Endosymbiotic Wolbachia bacteria are potent modulators of pathogen infection and transmission in multiple naturally and artificially infected insect species, including important vectors of human pathogens. Anopheles mosquitoes are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus. Recent techniques have enabled establishment of somatic Wolbachia infections in Anopheles. Here, we characterize somatic infections of two diverse Wolbachia strains (wMelPop and wAlbB) in Anopheles gambiae, the major vector of human malaria. After infection, wMelPop disseminates widely in the mosquito, infecting the fat body, head, sensory organs and other tissues but is notably absent from the midgut and ovaries. Wolbachia initially induces the mosquito immune system, coincident with initial clearing of the infection, but then suppresses expression of immune genes, coincident with Wolbachia replication in the mosquito. Both wMelPop and wAlbB significantly inhibit Plasmodium falciparum oocyst levels in the mosquito midgut. Although not virulent in non-bloodfed mosquitoes, wMelPop exhibits a novel phenotype and is extremely virulent for approximately 12–24 hours post-bloodmeal, after which surviving mosquitoes exhibit similar mortality trajectories to control mosquitoes. The data suggest that if stable transinfections act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control the Anopheles mosquitoes that transmit malaria

Metabolic pathway alignment between species using a comprehensive and flexible similarity measure

Comparative analysis of metabolic networks in multiple species yields important information on their evolution, and has great practical value in metabolic engineering, human disease analysis, drug design etc. In this work, we aim to systematically search for conserved pathways in two species, quantify their similarities, and focus on the variations between themElectrical Engineering, Mathematics and Computer Scienc