Posterior Medians Research Articles

Bayesian Knowledge Infusion for Studying Historical Sunspot Numbers

A scientific method that proposes a value Y to estimate a target value ρ is often subject to some level of uncertainty. In the Bayesian framework, the level of uncertainty can be measured by the width of the 68% interval, which is the range of the middle 68% of the ranked ρ values sampled from the posterior distribution p(ρ|Y). This paper considers Bayesian knowledge infusion (BKI) to reduce the uncertainty of the posterior distribution p(ρ|Y) based on additional knowledge that an event A happens. BKI is achieved by using a conditional prior distribution p(ρ|A) in the Bayes theorem, assuming that given the true ρ, its error-contaminated value Y is independent of event A. We use two examples to illustrate how to study whether or not it is possible to reduce uncertainty from 14C reconstruction (Y) of the annual sunspot number (SSN) (ρ) by infusing additional information (A) using BKI. Information (A) that SSN is from a year that has a Far Eastern record of naked eye sunspots is found to be not so effective in reducing the uncertainty. In contrast, information that SSN is from a year at a cycle minimum is found to be very effective, producing much narrower 68% intervals. The resulting Bayesian point estimates of SSN (the posterior medians of ρ) are cross-validated and tested on a subset of telescopically observed SSNs that were unused in the process of Bayes computation.

Bayesian true prevalence estimation of brucellosis in sheep, goats, cattle and camels in southeast regions of Iran.

Brucellosis is worldwide one of the most prevalent zoonotic diseases with serious public health hazard affecting domestic livestock and causing economic losses. Objective of this study is to estimate the true prevalence of brucellosis in livestock, specifically cattle, sheep, goats and camels, using a novel Bayesian latent class model, adjusting for the imperfect sensitivity and specificity of the applied tests, where the second test was restricted only to first test-positive samples. Brucellosis seems more prevalent in goats and sheep, while the posterior medians and 95% probability intervals (95% PI) for the average true prevalence for sheep, goats, cattle and camels are 18% (4%-43%), 19% (7%-37%), 16% (5%-34%) and 18% (1%-48%) respectively. The study results indicate that brucellosis is highly endemic in Iran and crucial steps are needed to control and raise awareness about the high public health concern of the disease.

As Simple as Possible but No Simpler: Optimizing the Performance of Neural Net Emulators for Galaxy SED Fitting

Artificial neural network emulators have been demonstrated to be a very computationally efficient method to rapidly generate galaxy spectral energy distributions, for parameter inference or otherwise. Using a highly flexible and fast mathematical structure, they can learn the nontrivial relationship between input galaxy parameters and output observables. However, they do so imperfectly, and small errors in flux prediction can yield large differences in recovered parameters. In this work, we investigate the relationship between an emulator’s execution time, uncertainties, correlated errors, and ability to recover accurate posteriors. We show that emulators can recover consistent results to traditional fits, with a precision of 25%–40% in posterior medians for stellar mass, stellar metallicity, star formation rate, and stellar age. We find that emulation uncertainties scale with an emulator’s width N as ∝N −1, while execution time scales as ∝N 2, resulting in an inherent tradeoff between execution time and emulation uncertainties. We also find that emulators with uncertainties smaller than observational uncertainties are able to recover accurate posteriors for most parameters without a significant increase in catastrophic outliers. Furthermore, we demonstrate that small architectures can produce flux residuals that have significant correlations, which can create dangerous systematic errors in colors. Finally, we show that the distributions chosen for generating training sets can have a large effect on an emulator’s ability to accurately fit rare objects. Selecting the optimal architecture and training set for an emulator will minimize the computational requirements for fitting near-future large-scale galaxy surveys. We release our emulators on GitHub (http://github.com/elijahmathews/MathewsEtAl2023).

Implications of the maximum modelled age on the estimation of natural mortality when using a meta-analytic prior: The example of eastern Australian orange roughy (Hoplostethus atlanticus)

The eastern Australian stock of orange roughy (Hoplostethus atlanticus) is a deep-water, long-lived species with a history of considerable exploitation during the late 1980s and early 1990s before being reduced to around 10% of unfished spawning biomass only a few years later, resulting in the closure of the fishery in 2006. Recent assessments have shown an increase in biomass, and the fishery was re-opened to targeted fishing in 2015. The stock is an example of the consequences of over-exploitation and of managed recovery. As such, conservation groups and fisheries managers are very interested in the status and future of the stock. Consequently, the assessment is both contentious and highly scrutinised. The current assessment uses the Stock Synthesis platform, with key inputs being annual catches, occasional acoustic surveys and age-composition data. Natural mortality (M) has been fixed at 0.04 yr−1 in the model on which management advice was based for several assessment cycles, but the maximum likelihood estimate of M is closer to 0.03 yr−1. Reducing the assumed value for M would lead to large reductions in catch, as determined by the Australian harvest control rule. A prior for M was developed based on assessments of orange roughy stocks in New Zealand and included in a Bayesian analysis in which M was treated as an estimable parameter. The median of the posterior for M is 0.0353 yr−1 when the maximum age in the assessment (i.e., the ‘plus-group age’) is set to 80 years, but setting the plus-group age to 80 is not based on analysis of data. Increasing the plus-group age to 100 and 120 years leads to posterior medians for M of 0.0381 and 0.0393 yr−1 respectively. This has consequences for catch limits under the Australian harvest control rule, with models that have older plus-group ages having higher estimated productivity and recommended biological catches. The results highlight the value of making use of the results from assessments of similar species to develop priors for M, especially for species that are poorly represented in the data sets on which current meta-analyses are based, and for the need to consider the choice of plus-group age when conducting assessments, particularly for long-lived species.

Inferential power in identifying frequency-dependent social learning strengthened by increasing behavioural options.

Two-option choice experimental designs are the most commonly employed framework for identifying evidence of social learning or social learning strategies in captive and wild populations. In nature, however, animals often choose from more than two behaviours, and multiple innovations may arise simultaneously. Studies of animal social learning are often constrained by small sample sizes, which limit researchers' ability to convincingly identify the proposed social learning strategy responsible for behavioural choice. In this study, I examine whether expanding behavioural options from k=2 to k > 2 and increasing sample size affects inferential power in identifying social learning strategies. I focus on three frequency-dependent learning strategies: conformist transmission, unbiased transmission and anti-conformist transmission. I simulate 100 datasets for 72 parameter combinations, yielding 7200 simulations. I evaluate number of options (k=2, 3, 4, 5), population size (n=5, 10, 25, 50, 100, 250) and the logarithmic strength of frequency dependence (log(f)=log(1∕3), log(1), log(3)). I then fit a Bayesian social learning model to simulated data to evaluate the percent of the posterior consistent with type of frequency dependence, posterior standard deviations, highest posterior density intervals and posterior medians relative to the true simulated value of log(f). I show that increasing the number of options an animal can choose from increases the accuracy and certainty of identifying the type and magnitude of frequency-dependent social learning. These effects are particularly pronounced at small to intermediate sample sizes, which are common in empirical studies of animal social learning. These findings suggest that knowing what an animal did not choose is equally important as knowing what an animal did choose when identifying social learning strategies. By strategically increasing the number of behaviours from which an animal can choose, researchers can increase inferential power in identifying social learning strategies without increasing sample size, that is, adding additional animals or collecting more data.

Bayesian approach for genetic analysis of production and reproduction traits in Jersey crossbred cattle

The knowledge of genetic parameters of performance traits is crucial for any breeding programme in dairy animals. The present study was conducted to use a Bayesian approach for estimation of genetic parameters of production and reproduction traits in Jersey crossbred cattle. Data of Jersey crossbred cattle maintained at Eastern Regional Station, National Dairy Research Institute, West Bengal spread over a span of 41 years were utilized. The marginal posterior medians of heritability for 305-day milk yield (305MY), total milk yield (TMY), peak yield (PY), lactation length (LL), calving interval (CI), total milk yield per day of lactation length (TMY/LL) and total milk yield per day of calving interval (TMY/CI) were 0.31 ± 0.07, 0.29 ± 0.07, 0.27 ± 0.06, 0.16 ± 0.05, 0.15 ± 0.05, 0.29 ± 0.06, 0.27 ± 0.06, respectively. Moderate heritability estimates for 305MY, TMY, PY and production efficiency traits indicate the presence of adequate additive genetic variance in these traits to respond to selection combined with better herd management. Repeatability estimates for 305MY, TMY, PY, LL, CI, TMY/LL and TMY/CI were 0.57 ± 0.08, 0.58 ± 0.08, 0.51 ± 0.07, 0.34 ± 0.06, 0.31 ± 0.06, 0.54 ± 0.07 and 0.49 ± 0.07, respectively. Repeatability estimates for 305MY, TMY and PY were high in the current study, suggesting the use of first lactation records for early evaluation of Jersey crossbred cattle for future selection. Genetic correlations varied from 0.21 to 0.97 and maximum genetic correlation was observed between 305MY and TMY indicating that consideration of 305MY instead of TMY in breeding programmes would suffice. Positive genetic correlations of CI with 305MY and TMY indicated the antagonistic association between production and reproduction traits.

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Illustrating a Species Sensitivity Distribution for Nano- and Microplastic Particles Using Bayesian Hierarchical Modeling.

Environmental contamination with nano‐ and microplastic (NMP) particles is an emerging global concern. The derivation of species sensitivity distributions (SSDs) is an essential step in estimating a hazardous concentration for 5% of the species (HC5), and this HC5 value is often used as a “safe” concentration in ecological risk assessment, that is, predicted‐no‐effect concentration. Although properties of plastics such as particle size can affect toxic effect concentrations, such influences have not yet been quantitatively considered in estimating SSDs for NMP particles. We illustrate a log‐normal SSD using chronic lowest‐observed‐effect concentrations (LOECs) of NMP particles from readily available toxicity data sets, considering the influence of particle size, polymer type, and freshwater or marine test media by adopting Bayesian hierarchical modeling techniques. Results of the hierarchical SSD modeling suggest that the SSD mean was negatively associated with particle size and was lower in marine media than in freshwater media. The posterior medians of the HC5 estimated from the LOEC‐based SSD varied by a factor of 10 depending on these factors (e.g., 1.8–20 μg/L for the particle size range of 0.1–5000 μm in the marine environment). Hierarchical SSD modeling allows us to clarify the influences of important factors such as NMP properties on effect concentrations, thereby helping to guide more relevant ecological risk assessments for NMP. Environ Toxicol Chem 2022;41:954–960. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Similar Clinical Outcomes in Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease Treated with Canakinumab: Bayesian and Population Model-Based Analyses.

IntroductionSystemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) represent pediatric and adult variants of the Still’s disease continuum. To determine whether clinical outcomes between patients with sJIA and AOSD were similar, Bayesian and population model-based analyses were conducted on endpoints from studies of canakinumab in both patient populations. The objective was to further support the efficacy of canakinumab in patients with AOSD.MethodsA Bayesian analysis of endpoints from a study of canakinumab in AOSD was conducted borrowing information from five pooled sJIA studies using a robust meta-analytic predictive (MAP) approach. Similarity of clinical outcomes across populations was fulfilled if the AOSD study posterior median fell within the 95% predicted credible interval for the outcome of interest, based on the pooled sJIA data. Population model-based analyses (pharmacokinetic [PK] and PK/pharmacodynamic [PKPD]) were conducted to compare the pharmacokinetics and exposure–response relationships between populations.ResultsThe AOSD study posterior medians for adapted American College of Rheumatology (ACR)30 response, continuous adapted ACR response, number of active joints, C-reactive protein, and absence of fever were within the 95% credible interval for the prediction of the MAP analysis from the pooled sJIA data, supporting the similarity in outcomes between patient populations. PK analysis demonstrated comparable exposure across sJIA age groups and patients with AOSD. PKPD relationships were consistent across patient populations. Analyses indicated that no therapeutic benefit can be expected from a dose increase in patients with AOSD.ConclusionThe analyses presented support the similarity of clinical outcomes following treatment with canakinumab in patients with sJIA and AOSD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00422-9.

Impact of complex, partially nested clustering in a three-arm individually randomized group treatment trial: A case study with the wHOPE trial.

When participants in individually randomized group treatment trials are treated by multiple clinicians or in multiple group treatment sessions throughout the trial, this induces partially nested clusters which can affect the power of a trial. We investigate this issue in the Whole Health Options and Pain Education trial, a three-arm pragmatic, individually randomized clinical trial. We evaluate whether partial clusters due to multiple visits delivered by different clinicians in the Whole Health Team arm and dynamic participant groups due to changing group leaders and/or participants across treatment sessions during treatment delivery in the Primary Care Group Education arm may impact the power of the trial. We also present a Bayesian approach to estimate the intraclass correlation coefficients. We present statistical models for each treatment arm of Whole Health Options and Pain Education trial in which power is estimated under different intraclass correlation coefficients and mapping matrices between participants and clinicians or treatment sessions. Power calculations are based on pairwise comparisons. In practice, sample size calculations depend on estimates of the intraclass correlation coefficients at the treatment sessions and clinician levels. To accommodate such complexities, we present a Bayesian framework for the estimation of intraclass correlation coefficients under different participant-to-session and participant-to-clinician mapping scenarios. We simulated continuous outcome data based on various clinical scenarios in Whole Health Options and Pain Education trial using a range of intraclass correlation coefficients and mapping matrices and used Gibbs samplers with conjugate priors to obtain posteriors of the intraclass correlation coefficients under those different scenarios. Posterior means and medians and their biases are calculated for the intraclass correlation coefficients to evaluate the operating characteristics of the Bayesian intraclass correlation coefficient estimators. Power for Whole Health Team versus Primary Care Group Education is sensitive to the intraclass correlation coefficient in the Whole Health Team arm. In these two arms, an increased number of clinicians, more evenly distributed workload of clinicians, or more homogeneous treatment group sizes leads to increased power. Our simulation study for the intraclass correlation coefficient estimation indicates that the posterior mean intraclass correlation coefficient estimator has less bias when the true intraclass correlation coefficients are large (i.e. 0.10), but when the intraclass correlation coefficient is small (i.e. 0.01), the posterior median intraclass correlation coefficient estimator is less biased. Knowledge of intraclass correlation coefficients and the structure of clustering are critical to the design of individually randomized group treatment trials with partially nested clusters. We demonstrate that the intraclass correlation coefficient of the Whole Health Team arm can affect power in the Whole Health Options and Pain Education trial. A Bayesian approach provides a flexible procedure for estimating the intraclass correlation coefficients under complex scenarios. More work is needed to educate the research community about the individually randomized group treatment design and encourage publication of intraclass correlation coefficients to help inform future trial designs.

Efficacy and Tolerability of Evogliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis with Bayesian Inference Through a Quality-management System

PurposeEvogliptin is one of the latest dipeptidyl peptidase-4 (DPP-4) inhibitor, and a number of clinical trials have been performed following its development, including several randomized controlled trials (RCTs) performed to evaluate its efficacy and tolerability. In our study, we performed a systematic review and meta-analysis of its efficacy and tolerability by collecting RCTs and confirmed the results with Bayesian inference. Moreover, an updated quality-management system was integrated into the study process of systematic review. MethodsPubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for literature published between May 1990 and November 2020. We selected 6 homogeneous RCTs in 1017 subjects for efficacy and 1070 subjects for tolerability analysis. Regarding the efficacy profile, the mean differences from baseline (95% CIs) in hemoglobin (Hb) A1c and fasting plasma glucose (FPG) were generated as end points and derived from each study. Regarding the tolerability profile, risk ratios of adverse events (AEs), serious AEs, adverse drug reactions, and hypoglycemia were generated from baseline to outcome measurements as derived from each study. A subsequent meta-analysis was performed with Bayesian inference. FindingsFor HbA1c and FPG, the results suggested a statistically significant improvement with evogliptin versus placebo (HbA1c, −0.44 [95% CI, −0.54 to −0.34; P < 0.00001] and posterior median, −0.38 [95% CI, −0.51 to −0.24]; FPG, −0.61 [95% CI, −0.90 to −0.31; P < 0.0001] and posterior median, −0.48 [95% CI, −0.90 to −0.16]), but no statistically significant difference with evogliptin versus other DPP-4 inhibitors (HbA1c, −0.01 [95% CI, −0.14 to 0.12] and posterior median, −0.06 [95% CI, −0.25 to 0.12]; FPG, 0.17 [95% CI, −0.10 to 0.44] and posterior median, 0.27 [95% CI, −0.12 to 0.65]). In terms of tolerability, the overall prevalence of adverse events, including hypoglycemia, was similar between evogliptin and other DPP-4 inhibitors and placebo. ImplicationsEvogliptin appears more efficacious in terms of changes in HbA1c and FPG compared with placebo, with an efficacy comparable to those of other DPP-4 inhibitors, although with the limited data studied and the minuscule sample sizes, the predictions of posterior medians, mean differences, and risk ratios of HbA1c, FPG, and AEs by Bayesian inference were consistent with our findings through our quality-management system.

Spatio-temporal modelling of municipal waste management systems’ meta-efficiency scores

ABSTRACT This paper describes an approach to measure the intensity and the territorial dispersion of spatial proximity effects, which affect efficiency scores obtained through data envelopment analysis in the field of municipal waste management systems (MWMSs). In particular, we show that these analyses cannot be conducted by relying on efficiency scores that are not comparable over time and treated as cross-sectional data, as is done in most previous studies. Instead, the use of panel data is a key element to obtain reliable results. We used a meta-frontier approach to obtain meta-efficiency scores comparable over time and a modified conditional autoregressive (CAR) model to provide an estimation of the intensity of spatial proximity effects. This approach was applied to data on 277 MWMSs located in the Italian region of Abruzzo. Our method provides useful information for policymakers. In particular, the areas in which stagnating and suboptimal performance can be expected over time can be identified by plotting over the regional territory the posterior medians of the random effects obtained by the spatial component of the CAR model together with the highly efficient municipalities. To improve efficiency, these areas require an active intervention by levels of government higher than the municipal level.

Late 19th century navigational uncertainties and their influence on sea surface temperature estimates

Accurate estimates of historical changes in sea surface temperatures (SSTs) and their uncertainties are important for documenting and understanding historical changes in climate. A source of uncertainty that has not previously been quantified in historical SST estimates stems from position errors. A Bayesian inference framework is proposed for quantifying errors in reported positions and their implications on SST estimates. The analysis framework is applied to data from the International Comprehensive Ocean-Atmosphere Data Set (ICOADS3.0) in 1885, a time when astronomical and chronometer estimation of position was common but predated the use of radio signals. Focus is upon a subset of 943 ship tracks from ICOADS3.0 that report their position every two hours to a precision of 0.01∘ longitude and latitude. These data are interpreted as positions determined by dead reckoning that are periodically updated by celestial correction techniques. The posterior medians of uncertainties in celestial correction are 33.1 km (0.30∘ on the equator) in longitude and 24.4 km (0.22∘) in latitude, respectively. Celestial navigation uncertainties being smaller in latitude than longitude is qualitatively consistent with the relative difficulty of obtaining astronomical estimates. The posterior medians for two-hourly dead reckoning uncertainties are 19.2% for ship speed and 13.2∘ for ship heading, leading to random position uncertainties with median 0.18∘ (20 km on the equator) in longitude and 0.15∘ (17 km) in latitude. Reported ship tracks also contain systematic position uncertainties relating to precursor dead-reckoning positions not being updated after obtaining celestial position estimates, indicating that more accurate positions can be provided for SST observations. Finally, we translate position errors into SST uncertainties by sampling an ensemble of SSTs from the Multiscale Ultrahigh Resolution Sea Surface Temperature (MURSST) data set. Evolving technology for determining ship position, heterogeneous reporting and archiving of position information, and seasonal and spatial changes in navigational uncertainty and SST gradients together imply that accounting for positional error in SST estimates over the span of the instrumental record will require substantial additional effort.

Estimates of Occupational Inhalation Exposures to Six Oil-Related Compounds on the Four Rig Vessels Responding to the Deepwater Horizon Oil Spill.

The 2010 Deepwater Horizon (DWH) oil spill involved thousands of workers and volunteers to mitigate the oil release and clean-up after the spill. Health concerns for these participants led to the initiation of a prospective epidemiological study (GuLF STUDY) to investigate potential adverse health outcomes associated with the oil spill response and clean-up (OSRC). Characterizing the chemical exposures of the OSRC workers was an essential component of the study. Workers on the four oil rig vessels mitigating the spill and located within a 1852 m (1 nautical mile) radius of the damaged wellhead [the Discoverer Enterprise (Enterprise), the Development Driller II (DDII), the Development Driller III (DDIII), and the HelixQ4000] had some of the greatest potential for chemical exposures. The aim of this paper is to characterize potential personal chemical exposures via the inhalation route for workers on those four rig vessels. Specifically, we presented our methodology and descriptive statistics of exposure estimates for total hydrocarbons (THCs), benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H) for various job groups to develop exposure groups for the GuLF STUDY cohort. Using descriptive information associated with the measurements taken on various jobs on these rig vessels and with job titles from study participant responses to the study questionnaire, job groups [unique job/rig/time period (TP) combinations] were developed to describe groups of workers with the same or closely related job titles. A total of 500 job groups were considered for estimation using the available 8139 personal measurements. We used a univariate Bayesian model to analyze the THC measurements and a bivariate Bayesian regression framework to jointly model the measurements of THC and each of the BTEX-H chemicals separately, both models taking into account the many measurements that were below the analytic limit of detection. Highest THC exposures occurred in TP1a and TP1b, which was before the well was mechanically capped. The posterior medians of the arithmetic mean (AM) ranged from 0.11 ppm ('Inside/Other', TP1b, DDII; and 'Driller', TP3, DDII) to 14.67 ppm ('Methanol Operations', TP1b, Enterprise). There were statistical differences between the THC AMs by broad job groups, rigs, and time periods. The AMs for BTEX-H were generally about two to three orders of magnitude lower than the THC AMs, with benzene and ethylbenzene measurements being highly censored. Our results add new insights to the limited literature on exposures associated with oil spill responses and support the current epidemiologic investigation of potential adverse health effects of the oil spill.

HALO7D II: The Halo Velocity Ellipsoid and Velocity Anisotropy with Distant Main-sequence Stars

Abstract The Halo Assembly in Lambda Cold Dark Matter: Observations in 7 Dimensions (HALO7D) data set consists of Keck II/DEIMOS spectroscopy and Hubble Space Telescope–measured proper motions of Milky Way halo main-sequence turnoff stars in the CANDELS fields. In this paper, the second in the HALO7D series, we present the proper motions for the HALO7D sample. We discuss our measurement methodology, which makes use of a Bayesian mixture modeling approach for creating the stationary reference frame of distant galaxies. Using the 3D kinematic HALO7D sample, we estimate the parameters of the halo velocity ellipsoid, , and the velocity anisotropy β. Using the full HALO7D sample, we find at kpc. We also estimate the ellipsoid parameters for our sample split into three apparent magnitude bins; the posterior medians for these estimates of β are consistent with one another. Finally, we estimate β in each of the individual HALO7D fields. We find that the velocity anisotropy β can vary from field-to field, which suggests that the halo is not phase-mixed at . We explore the β variation across the skies of two stellar halos from the Latte suite of FIRE-2 simulations, finding that both simulated galaxies show β variation over a range similar to that of the variation observed across the four HALO7D fields. The accretion histories of the two simulated galaxies result in different β variation patterns; spatially mapping β is thus a way forward in characterizing the accretion history of the Galaxy.

A diverse new spider (Araneae) fauna from the Jinju Formation, Cretaceous (Albian) of Korea

A collection of spiders from the Cretaceous (Albian) Jinju Formation of Korea is described. These finds increase the number of known spiders from the Jinju Formation from one to 11. There is considerable diversity of mygalomorphs and araneomorphs, including palpimanoids (including lagonomegopids), as well as cribellate and ecribellate entelegynes. Such diversity among so few specimens hints that an even greater range of families will come to light as more specimens are discovered in the future. The first non-amber Lagonomegopidae are described, with the first preservation of a spider eye tapetum in the fossil record, providing evidence for lagonomegopid enlarged eyes being posterior medians. The female-biased sex ratio of lagonomegopids is discussed and it is concluded that the bias is fortuitous.http://zoobank.org/urn:lsid:zoobank.org:pub:7926A54F-1B64-417E-91B4-027FAFCC8C0A

Risk of Venous Thromboembolism in Acute Leukemias: A Meta-Analysis

Background: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients (pts). The risk of VTE, however, differs according to cancer type. Pts with hematologic malignancies are at an increased risk of VTE events, either due to the underlying disease biology or related to treatment. This risk exists even in acute leukemia (AL), which is characterized by profound thrombocytopenia and coagulopathies that present treatment challenges. Advances in anti-leukemic therapies and improved supportive care over the last several decades may have impacted the extent to which an average patient is at risk for VTE We performed a meta-analysis of published literature on VTE rates in AL pts and evaluated trends in VTE incidence in relation to the reported study time period.Methods: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, EMBASE, Medline, Scopus and Cochran databases to identify relevant studies published between January 1980 and June 2018. All studies including randomized controlled, retrospective or observational studies in AL pts which investigated VTE as an endpoint were included. Abstracts, posters, review articles, and case reports were excluded. Articles were excluded if they did not provide disease-level data. The search terms included “venous thromboembolism”, “deep venous thrombosis”, “pulmonary embolism”, and “leukemia”. Furthermore, citations were supplemented by cross checking the reference lists of eligible studies and relevant reviews to identify additional published data. We collected study period, study design, study publication date, AL subtype, total patients, and rates of VTE. When reported, we collected information on VTE prophylaxis and presence of central lines. Meta-analysis of VTE rates was performed using an established Bayesian logistic random effects model. The model assumes that the log odds of VTE is exchangeable across studies with Gaussian distribution and random hierarchical mean and standard deviation. For both analyses, the hierarchical mean assumed a Gaussian prior with mean 0 and variance = 200. The inter-study standard deviation was assumed uniform (0,10). Given treatment and patient heterogeneity among distinct subtypes of AL, analyses were undertaken separately for each AL subtype. Results for individual studies and the combined inter-study mean VTE rate are described by the resultant posterior medians and 95% highest posterior density (HPD) intervals.Results: From the initial search, 2527 articles were identified. Among these, 938 were duplicate publications, 1408 did not meet content inclusion criteria, 150 were review articles or case reports, 2 studies lacked disease level data, thus, leaving 31 studies for analysis. A total of 29 studies focused on ALL, 11 on AML, 11 on APL, and some studies included multiple disease populations. The inter-study mean incidence of VTE for ALL was 8.67% (95% HPD 6.01%-11.58%), fig 1a, for AML was 7.25% (95% HPD 4.12%-11.09%), fig 1b, and for APL was 12.94% (95% HPD 7.04%-20.67%), fig 1c. .. Our graphical analysis indicates an increase in risk of VTE with time for ALL (fig 2a), AML (fig 2b), and APL (fig 2c).Conclusion: In the present meta-analysis, we determined that the overall incidence of VTE in AL pts ranged from 7-13%. Among AL subtypes, APL pts had the highest rate of VTE. We observed an increased risk of VTE over time. We postulate this is multifactorial and may be related to an increase in case findings from increased screening, aging sedentary population, and increased use of prothombotic agents. Notable strengths of this study include the largest review of association of VTE with AL and evolving risk of VTE with time. These findings need to be considered in light of several limitations - lack of comparator group limiting ability to generate pooled relative risks for VTE, heterogeneity in study populations and reporting and scare data on VTE prophylaxis. Further data are required to determine the mechanism for the increase in risk. Given the VTE risk and its known impact on morbidity, mortality and associated health care costs, prospective studies are warranted in AL pts to facilitate establishment of guidelines for prophylaxis and management of thrombotic complications. DisclosuresCarraway:Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; FibroGen: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Speakers Bureau. Advani:Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding. Nazha:MEI: Consultancy. Gerds:Apexx Oncology: Consultancy; Celgene: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Quantitative Constraints on the Reionization History from the IGM Damping Wing Signature in Two Quasars at z &gt; 7

Abstract During reionization, neutral hydrogen in the intergalactic medium (IGM) imprints a damping wing absorption feature on the spectrum of high-redshift quasars. A detection of this signature provides compelling evidence for a significantly neutral universe, and enables measurements of the hydrogen neutral fraction x H i (z) at that epoch. Obtaining reliable quantitative constraints from this technique, however, is challenging due to stochasticity induced by the patchy inside-out topology of reionization, degeneracies with quasar lifetime, and the unknown unabsorbed quasar spectrum close to rest-frame Lyα. We combine a large-volume semi-numerical simulation of reionization topology with 1D radiative transfer through high-resolution hydrodynamical simulations of the high-redshift universe to construct models of quasar transmission spectra during reionization. Our state-of-the-art approach captures the distribution of damping wing strengths in biased quasar halos that should have reionized earlier, as well as the erosion of neutral gas in the quasar environment caused by its own ionizing radiation. Combining this detailed model with our new technique for predicting the quasar continuum and its associated uncertainty, we introduce a Bayesian statistical method to jointly constrain the neutral fraction of the universe and the quasar lifetime from individual quasar spectra. We apply this methodology to the spectra of the two quasars with the highest redshifts known, ULAS J1120+0641 and ULAS J1342+0928, and measure volume-averaged neutral fractions and (posterior medians and 68% credible intervals) when marginalized over quasar lifetimes of 103 ≤ t q ≤ 108 yr.

A network meta-analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation.

A wide selection of Interdental Oral Hygiene (IOH) aids is available to consumers. Recommendations for selection are, however, limited by the lack of direct comparisons in available studies. We aimed to assess the comparative efficacy of IOH aids using Bayesian Network Meta-Analysis (BNMA). Two independent reviewers performed a systematic literature review of randomized clinical trials assessing IOH aids, based on a focused question. Gingival inflammation (Gingival Index (GI), Bleeding-on-probing (BOP)) was the primary outcome and plaque and probing depth were secondary outcomes A random-effects arm-based BNMA model was run for each outcome; posterior medians and 95% credible-intervals (CIs) summarized marginal distributions of parameters. A two-phase selection process identified 22 trials assessing 10 IOH aids as brushing adjuncts. Interdental brushes (IB) yielded the largest reduction in GI (0.23 [95% CI: 0.09, 0.37]) as toothbrushing adjuncts, followed by water-jet (WJ) (0.19 [95% CI: 0.14, 0.24]). Rankings based on posterior probabilities revealed that IB and WJ had the highest probability of being "best" (64.7% and 27.4%, respectively) for GI reduction, whereas the probability for toothpick and floss being the "best" IOH aids was near zero. Notably, except for toothpicks, all IOH aids were better at reducing GI as compared with control. BNMA enabled us to quantitatively evaluate IOH aids and provide a global ranking of their efficacy. Interdental brushes and water-jets ranked high for reducing gingival bleeding, whereas toothpicks and floss ranked last. The patient-perceived benefit of IOH aids is not clear because gingival inflammation measures are physical indicators of periodontal health.

Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions.