Modest Bias Research Articles

How to study political activists: A petition survey approach

A major challenge for social movement and political campaign studies is generating large, representative samples of political activists. This paper outlines a strategy of surveying those who participate in a common, baseline form of political action: signing petitions. Similar to protest surveys, signing a petition constitutes a more baseline low cost/low risk form of political activism. In 26 states in the U.S. petition lists are public record and, with modest effort, can be used to study a wide variety of issues, groups and campaigns. We outline the steps and costs involved in such a petition survey and how to improve response rate. To assess response bias, we compare demographic and political affiliation measures acquired from a marketing analytics company (Experian) for respondents and non-respondents to our survey of petition signers for two state-level initiative elections, finding only modest and interpretable response bias. The methods presented here have broader implications for survey research in general.

Selective Proton/Deuteron Transport through Nafion|Graphene|Nafion Sandwich Structures at High Current Density.

Ion current densities near 1 A cm-2 at modest bias voltages (<200 mV) are reported for proton and deuteron transmission across single-layer graphene in polyelectrolyte-membrane (PEM)-style hydrogen pump cells. The graphene is sandwiched between two Nafion membranes and covers the entire area between two platinum-carbon electrodes, such that proton transfer is forced to occur through the graphene layer. Raman spectroscopy confirms that buried graphene layers are single-layer and relatively free of defects following the hot-press procedure used to make the sandwich structures. Area-normalized ion conductance values of approximately 29 and 2.1 S cm-2 are obtained for proton and deuteron transport, respectively, through single-layer graphene, following correction for contributions to series resistance from Nafion resistance, contact resistance, etc. These ion conductance values are several hundred to several thousand times larger than in previous reports on similar phenomena. A ratio of proton to deuteron conductance of 14 to 1 is obtained, in good agreement with but slightly larger than those in prior reports on related cells. Potassium ion transfer rates were also measured and are attenuated by a factor of many thousands by graphene, whereas proton transfer is attenuated by graphene by only a small amount. Rates for hydrogen and deuterium ion exchange across graphene were analyzed using a model whereby each hexagonal graphene hollow site is assumed to transmit ions with a specific per-site ion-transfer self-exchange rate constant. Rate constant values of approximately 2500 s-1 for proton transfer and 180 s-1 for deuteron transfer per site through graphene are reported.

Establishment and convergence of photosynthetic microbial biomats in shallow unit process open-water wetlands

The widespread adoption of engineered wetlands designed for water treatment is hindered by uncertainties in system reliability, resilience and management associated with coupled biological and physical processes. To better understand how shallow unit process open-water wetlands self-colonize and evolve, we analyzed the composition of the microbial community in benthic biomats from system establishment through approximately 3 years of operation. Our analysis was conducted across three parallel demonstration-scale (7500 m2) cells located within the Prado Constructed Wetlands in Southern California. They received water from the Santa Ana River (5.9 ± 0.2 mg/L NO3-N), a water body where the flow is dominated by municipal wastewater effluent from May to November. Phylogenetic inquiry and microscopy confirmed that diatoms and an associated aerobic bacterial community facilitated early colonization. After approximately nine months of operation, coinciding with late summer, an anaerobic community emerged with the capability for nitrate attenuation. Varying the hydraulic residence time (HRT) from 1 to 4 days the subsequent year resulted in modest ecological changes across the three parallel cells that were most evident in the outlet regions of the cells. The community that established at this time was comparatively stable for the remaining years of operation and converged with one that had previously formed approximately 550 km (350 miles) away in a pilot-scale (400 m2) wetland in Northern California. That system received denitrified (20.7 ± 0.7 mg/L NO3-N), secondary treated municipal wastewater for 5 years of operation. Establishment of a core microbiome between the two systems revealed a strong overlap of both aerobic and anaerobic taxa with approximately 50% of the analyzed bacterial sequences shared between the two sites. Additionally the same species of diatom, Stauirsa construens var. venter, was prolific in both systems as the putative dominant primary producer. Our results indicate that despite differences in scale, geographic location and source waters, the shallow open-water wetland design can select for a rapid convergence of microbial structure and functionality associated with the self-colonizing benthic biomat. This resulting biomat matures over the first growing season with operational parameters such as HRT further exerting a modest selective bias on community succession.

Bias from outcome misclassification in immunization schedule safety research

The Institute of Medicine recommended conducting observational studies of childhood immunization schedule safety. Such studies could be biased by outcome misclassification, leading to incorrect inferences. Using simulations, we evaluated (1) outcome positive predictive values (PPVs) as indicators of bias of an exposure-outcome association, and (2) quantitative bias analyses (QBA) for bias correction. Simulations were conducted based on proposed or ongoing Vaccine Safety Datalink studies. We simulated 4 studies of 2 exposure groups (children with no vaccines or on alternative schedules) and 2 baseline outcome levels (100 and 1000/100000 person-years), with 3 relative risk (RR) levels (RR=0.50, 1.00, and 2.00), across 1000 replications using probabilistic modeling. We quantified bias from non-differential and differential outcome misclassification, based on levels previously measured in database research (sensitivity>95%; specificity>99%). We calculated median outcome PPVs, median observed RRs, Type 1 error, and bias-corrected RRs following QBA. We observed PPVs from 34% to 98%. With non-differential misclassification and true RR=2.00, median bias was toward the null, with severe bias (median observed RR=1.33) with PPV=34% and modest bias (median observed RR=1.83) with PPV=83%. With differential misclassification, PPVs did not reflect median bias, and there was Type 1 error of 100% with PPV=90%. QBA was generally effective in correcting misclassification bias. In immunization schedule studies, outcome misclassification may be non-differential or differential to exposure. Overall outcome PPVs do not reflect the distribution of false positives by exposure and are poor indicators of bias in individual studies. Our results support QBA for immunization schedule safety research.

Microbial Photoelectrosynthesis for Self-Sustaining Hydrogen Generation.

Current artificial photosynthesis (APS) systems are promising for the storage of solar energy via transportable and storable fuels, but the anodic half-reaction of water oxidation is an energy intensive process which in many cases poorly couples with the cathodic half-reaction. Here we demonstrate a self-sustaining microbial photoelectrosynthesis (MPES) system that pairs microbial electrochemical oxidation with photoelectrochemical water reduction for energy efficient H2 generation. MPES reduces the overall energy requirements thereby greatly expanding the range of semiconductors that can be utilized in APS. Due to the recovery of chemical energy from waste organics by the mild microbial process and utilization of cost-effective and stable catalyst/electrode materials, our MPES system produced a stable current of 0.4 mA/cm2 for 24 h without any external bias and ∼10 mA/cm2 with a modest bias under one sun illumination. This system also showed other merits, such as creating benefits of wastewater treatment and facile preparation and scalability.

From Capacitance-Controlled to Diffusion-Controlled Electrochromism in Nb-Doped TiO2 Nanocrystalline Electrodes

N-doped transition-metal oxides nanocrystals are interesting candidates as active materials for near-infrared-selective electrochromic devices due to their peculiar optoelectronic properties arising from their outer-d valence electrons. Among them, TiO2 is particularly attractive, as it can be conveniently modified by substitutional aliovalent doping, using, for example, Nb5+ ions, to enhance electron conductivity and to induce the appearance of an intense surface plasmonic resonance in the near-infrared range. Four batches of Nb-doped TiO2 nanocrystals with different doping levels (from 0% to 15% of niobium content) have been here investigated and used as active electrodes in lab-scale electrochromic devices, capable of dynamically modulating the intensity of near-infrared radiation upon the application of a modest bias voltage. It has been then ascertained that an appropriate control of two fundamental electrochemical processes occurring at the interface with the electrolyte, namely the surface capacitive charging and Li+ insertion, makes possible to selectively (and independently) regulate their optical features over the “near-infrared only” and the “visible + near-infrared” regimes, respectively.

Effect of epilepsy in pregnancy on fetal growth restriction: a systematic review and meta-analysis.

Epilepsy is one of the most common neurological diseases during pregnancy. However, the influence of epilepsy on fetal growth is not understood. Thus, this study conducted a meta-analysis to determine the influence of epilepsy during pregnancy on fetal growth restriction (FGR). BIOSIS, Medline, Embase, and PubMed databases were searched between January 2000 and January 2016. Without imposing language or regional restrictions, referenced articles were selected. Final analysis included 684 citations from 11 studies. Estimated risk of FGR was 1.28-fold higher in epileptic pregnant women than in non-epileptic women [95% confidence interval (95% CI) 1.09-1.50, p<0.05]. Given the course of previous studies, hierarchical analysis of pregnant women who use antiepileptic drugs (AEDs) was conducted. Results show that FGR rate is significantly increased even if AEDs were taken [odds ratio 1.26, 95% CI 1.13-1.41, p<0.05]. Although modest bias cannot be avoided, our meta-analysis indicated that epilepsy participates in fetal development as an unfavorable factor, and AEDs seemed to be useless in decreasing the occurrence rate of FGR.

Meta-Analysis of Trauma-Focused Therapies for Treating the Symptoms of Posttraumatic Stress Disorder

This meta-analysis of 46 between-groups studies published between 1997 and 2015 detected treatment effects ranging from large to small when comparing trauma-focused therapies with no treatment (g = −1.05), supportive interventions (g = −0.91), other interventions (g = −0.57), and non-trauma-focused cognitive behavior therapies (g = −0.08) for the treatment of posttraumatic stress disorder (PTSD). The independent random-effects models detected modest publication bias and a negligible influence of moderating variables on treatment outcomes. Considerations for counselors who treat PTSD and suggestions for researchers are provided.

At-Risk Alcohol Use Among HIV-Positive Patients and the Completion of Patient-Reported Outcomes.

Heavy drinking is prevalent among people living with HIV. Studies use tools like patient-reported outcomes (PROs) to quantify alcohol use in a detailed, timely manner. However, if alcohol misuse influences PRO completion, selection bias may result. Our study included 14,145 adult HIV patients (133,036 visits) from CNICS who were eligible to complete PROs at an HIV primary care visit. We compared PRO completion proportions between patients with and without a clinical diagnosis of at-risk alcohol use in the prior year. We accounted for confounding by baseline and visit-specific covariates. PROs were completed at 20.8% of assessed visits. The adjusted difference in PRO completion proportions was -3.2% (95% CI -5.6 to -0.8%). The small association between receipt of an at-risk alcohol use diagnosis and decreased PRO completion suggests there could be modest selection bias in studies using the PRO alcohol measure.

Evaluation of a new random-access HBV DNA molecular assay: The VERIS HBV assay

BackgroundDetection and quantification of HBV DNA are essential to diagnose chronic HBV infection, monitor the virological response to treatment and the possible selection of resistant viruses in order to tailor therapy. The VERIS/MDx System HBV Assay is a random-access system that quantifies HBV DNA in clinical samples using unique single sample and reagent access during the workflow process without the need to reload other tests and delivers results within 1.2h following sampling. Objective and study designThe goal of this study was to evaluate the analytical performance of the VERIS HBV assay for HBV DNA detection and quantification in clinical samples from a series of patients chronically infected with different HBV genotypes. ResultsThe specificity of the VERIS HBV assay was estimated to be over 99.5%. The limit of detection (LOD) was estimated to be 4.1IU/mL (95%CI: 3.20–5.90IU/mL). Using an HBV linearity panel and controls (Seracare LifeScience), intra-assay and inter-assay coefficients of variation ranged from 0.12% to 3.64% and from 1.05% to 7.35%, respectively. The influence of the HBV genotype was evaluated from 120 clinical specimens containing HBV genotypes A to G tested in parallel with the VERIS HBV assay and the COBAS AmpliPrep/COBAS TaqMan HBV v2.0 assay. A linear relationship between the HBV DNA levels measured with both assays was found. A modest bias of HBV DNA levels was observed in the VERIS assay as compared to CAP/CTM HBV v2.0 in most of the samples tested (mean VERIS minus CAP/CTM difference: −0.395 log IU/mL). Overall, the VERIS HBV assay is well suited to monitoring clinical HBV DNA levels in infected patients according to current clinical practice guidelines.

Estimating the probability of clonal relatedness of pairs of tumors in cancer patients.

Next generation sequencing panels are being used increasingly in cancer research to study tumor evolution. A specific statistical challenge is to compare the mutational profiles in different tumors from a patient to determine the strength of evidence that the tumors are clonally related, that is, derived from a single, founder clonal cell. The presence of identical mutations in each tumor provides evidence of clonal relatedness, although the strength of evidence from a match is related to how commonly the mutation is seen in the tumor type under investigation. This evidence must be weighed against the evidence in favor of independent tumors from non-matching mutations. In this article, we frame this challenge in the context of diagnosis using a novel random effects model. In this way, by analyzing a set of tumor pairs, we can estimate the proportion of cases that are clonally related in the sample as well as the individual diagnostic probabilities for each case. The method is illustrated using data from a study to determine the clonal relationship of lobular carcinoma in situ with subsequent invasive breast cancers, where each tumor in the pair was subjected to whole exome sequencing. The statistical properties of the method are evaluated using simulations, demonstrating that the key model parameters are estimated with only modest bias in small samples in most configurations.

Organic photodiodes from homochiral l-proline derived squaraine compounds with strong circular dichroism.

We suggest and explore a novel route towards organic photodetectors sensitive to the circular polarization state of light. For this, we insert fullerene-blended thin films of homochiral squaraine compounds acting as a highly circular dichroic active layer into conventional bulk hetero-junction photodiodes. Initially, we discuss steady-state characterization of photodiodes with unpolarized light. The homochiral, l-proline derived squaraine compounds are obtained via a chiral pool synthesis in sizable quantities. The aggregation behavior of the two compounds with varying side chain length is complex. They exhibit H-type spectral signatures only in colloidal solution, and both H- and J-type features with large splitting in neat and fullerene-blended thin films. We probe strong excitonic circular dichroism for both aggregate species, showing the most competitive dissymmetry factors up to -0.055 in fullerene-blended thin films. We vary the blend ratio and layer thickness of such active layers in the photodiodes. The device performance is in all cases limited by a low fill factor which is accompanied by a voltage-dependent photocurrent. Current-voltage measurements show light intensity dependent characteristics, which are S-shaped, contrary to our expectations, only for thin active layers independent of the blend ratio. The external quantum efficiency is in some cases extraordinarily high, exceeding 100 percent in the blue spectral range under modest reverse bias voltages for thin, fullerene-rich devices. However, the most promising are the devices with thick, donor-rich layers defined by a spectral overlap of the strongest photocurrent response and the maximum circular dichroism within the green spectral range. Thus, we demonstrate the feasibility of combining photodiode functionality and strong circular dichroism as intrinsic material properties.

Measurement error in mobile source air pollution exposure estimates due to residential mobility during pregnancy.

Prenatal air pollution exposure is frequently estimated using maternal residential location at the time of delivery as a proxy for residence during pregnancy. We describe residential mobility during pregnancy among 19,951 children from the Kaiser Air Pollution and Pediatric Asthma Study, quantify measurement error in spatially resolved estimates of prenatal exposure to mobile source fine particulate matter (PM2.5) due to ignoring this mobility, and simulate the impact of this error on estimates of epidemiologic associations. Two exposure estimates were compared, one calculated using complete residential histories during pregnancy (weighted average based on time spent at each address) and the second calculated using only residence at birth. Estimates were computed using annual averages of primary PM2.5 from traffic emissions modeled using a Research LINE-source dispersion model for near-surface releases (RLINE) at 250 m resolution. In this cohort, 18.6% of children were born to mothers who moved at least once during pregnancy. Mobile source PM2.5 exposure estimates calculated using complete residential histories during pregnancy and only residence at birth were highly correlated (rS>0.9). Simulations indicated that ignoring residential mobility resulted in modest bias of epidemiologic associations toward the null, but varied by maternal characteristics and prenatal exposure windows of interest (ranging from -2% to -10% bias).

Uncertainties in stellar ages provided by grid techniques

AbstractThe determination of the age of single stars by means of grid‐based techniques is a well established method. We discuss the impact on these estimates of the uncertainties in several ingredients routinely adopted in stellar computations. The systematic bias on age determination caused by varying the assumed initial helium abundance, the mixing‐length and convective core overshooting parameters, and the microscopic diffusion are quantified and compared with the statistical error owing to the current uncertainty in the observations. The typical uncertainty in the observations accounts for 1ω statistical relative error in age determination ranging on average from about –35 % to +42 %, depending on the mass. However, the age's relative error strongly depends on the evolutionary phase and can be higher than 120 % for stars near the zero‐age main‐sequence, while it is typically about 20 % or lower in the advanced main‐sequence phase. A variation of ±1 in the helium‐to‐metal enrichment ratio induces a quite modest systematic bias on age estimates. The maximum bias due to the presence of the convective core overshooting is –7% for β = 0.2 and –13% for β = 0.4. The main sources of bias are the uncertainty in the mixing‐length value and the neglect of microscopic diffusion, which account each for a bias comparable to the random error uncertainty.

DNA Methylation Profiling of Uniparental Disomy Subjects Provides a Map of Parental Epigenetic Bias in the Human Genome

Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across ∼1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.

CLIMATE CHANGE AND LAND USE IN SOUTHEASTERN U.S.: DID THE “DUMB FARMER” GET IT WRONG?

The assumption of a fixed amount of land remaining in agriculture regardless of changing climate conditions — one of the features of the “dumb farmer scenario” — is likely to bias the estimated social welfare impacts of climate change. In order to quantify this bias, we employ a demand-supply framework to determine both the amount of land allocated to agricultural and nonagricultural uses as well as the social welfare associated with this allocation choice when no market distortions exist. We present an application of our model to the Southeastern United States and simulate the effects of changing climate conditions on land allocation in the region between 2007 and 2040. We find a very modest welfare bias when maintaining current farmland preservation policies and a more substantial bias if we assume that additional land policies are instituted which have spillover welfare effects in other land-using sectors.

Direct estimate of the rate of germline mutation in a bird.

The fidelity of DNA replication together with repair mechanisms ensure that the genetic material is properly copied from one generation to another. However, on extremely rare occasions when damages to DNA or replication errors are not repaired, germline mutations can be transmitted to the next generation. Because of the rarity of these events, studying the rate at which new mutations arise across organisms has been a great challenge, especially in multicellular nonmodel organisms with large genomes. We sequenced the genomes of 11 birds from a three-generation pedigree of the collared flycatcher (Ficedula albicollis) and used highly stringent bioinformatic criteria for mutation detection and used several procedures to validate mutations, including following the stable inheritance of new mutations to subsequent generations. We identified 55 de novo mutations with a 10-fold enrichment of mutations at CpG sites and with only a modest male mutation bias. The estimated rate of mutation per site per generation was 4.6 × 10−9, which corresponds to 2.3 × 10−9 mutations per site per year. Compared to mammals, this is similar to mouse but about half of that reported for humans, which may be due to the higher frequency of male mutations in humans. We confirm that mutation rate scales positively with genome size and that there is a strong negative relationship between mutation rate and effective population size, in line with the drift-barrier hypothesis. Our study illustrates that it should be feasible to obtain direct estimates of the rate of mutation in essentially any organism from which family material can be obtained.

Active recombinant Tol2 transposase for gene transfer and gene discovery applications.

BackgroundThe revolutionary concept of “jumping genes” was conceived by McClintock in the late 1940s while studying the Activator/Dissociation (Ac/Ds) system in maize. Transposable elements (TEs) represent the most abundant component of many eukaryotic genomes. Mobile elements are a driving force of eukaryotic genome evolution. McClintock’s Ac, the autonomous element of the Ac/Ds system, together with hobo from Drosophila and Tam3 from snapdragon define an ancient and diverse DNA transposon superfamily named hAT. Other members of the hAT superfamily include the insect element Hermes and Tol2 from medaka. In recent years, genetic tools derived from the ‘cut’ and ‘paste’ Tol2 DNA transposon have been widely used for genomic manipulation in zebrafish, mammals and in cells in vitro.ResultsWe report the purification of a functional recombinant Tol2 protein from E.coli. We demonstrate here that following microinjection using a zebrafish embryo test system, purified Tol2 transposase protein readily catalyzes gene transfer in both somatic and germline tissues in vivo. We show that purified Tol2 transposase can promote both in vitro cutting and pasting in a defined system lacking other cellular factors. Notably, our analysis of Tol2 transposition in vitro reveals that the target site preference observed for Tol2 in complex host genomes is maintained using a simpler target plasmid test system, indicating that the primary sequence might encode intrinsic cues for transposon integration.ConclusionsThis active Tol2 protein is an important new tool for diverse applications including gene discovery and molecular medicine, as well as for the biochemical analysis of transposition and regulation of hAT transposon/genome interactions. The measurable but comparatively modest insertion site selection bias noted for Tol2 is largely determined by the primary sequence encoded in the target sequence as assessed through studying Tol2 protein-mediated transposition in a cell-free system.Electronic supplementary materialThe online version of this article (doi:10.1186/s13100-016-0062-z) contains supplementary material, which is available to authorized users.

Cell Population Data and reflex testing rules of cell analysis in pleural and ascitic fluids using body fluid mode on Sysmex XN-9000

BackgroundAlthough optical microscopy (OM) remains the reference technique for analysis of ascitic (AF) and pleural (PF) fluids, novel hematological analyzers are equipped with modules for body fluid (BF) analysis. This study was aimed to analyze the performance of XN-BF module in Sysmex XN-9000, and to develop validation rules for automated cell counts in BFs. MethodsThe evaluation of XN-BF module included assessment of carryover, Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, data comparison with OM, and development of rules for assisting the validation of automated analysis of BFs and activating reflex testing. ResultsThe carryover was negligible. The LoB, LoD, LoQ and linearity were always excellent. The comparison with OM was characterized by Pearson's correlations ranging from r=0.50 to r=0.99 (p<0.001), modest bias and high diagnostic concordance (Area Under the Curve between 0.85 and 0.99). The use of instrument-specific cut-offs further increased diagnostic concordance. The implementation of reflex testing rules based on XN-BF data increased sensitivity and specificity of BFs classification to 0.98 and 0.95. ConclusionsOur results suggest that the XN-BF module on Sysmex-9000 may be a suitable alternative to OM for screening BF samples, especially when specific validation rules are used.

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

ObjectiveTo evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).MethodsPubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.ResultsA total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66).ConclusionsDespite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.