A mixed effect model for bivariate meta-analysis of diagnostic test accuracy studies using a copula representation of the random effects distribution

Diagnostic test accuracy studies typically report the number of true positives, false positives, true negatives and false negatives. There usually exists a negative association between the number of true positives and true negatives, because studies that adopt less stringent criterion for declaring a test positive invoke higher sensitivities and lower specificities. A generalized linear mixed model (GLMM) is currently recommended to synthesize diagnostic test accuracy studies. We propose a copula mixed model for bivariate meta-analysis of diagnostic test accuracy studies. Our general model includes the GLMM as a special case and can also operate on the original scale of sensitivity and specificity. Summary receiver operating characteristic curves are deduced for the proposed model through quantile regression techniques and different characterizations of the bivariate random effects distribution. Our general methodology is demonstrated with an extensive simulation study and illustrated by re-analysing the data of two published meta-analyses. Our study suggests that there can be an improvement on GLMM in fit to data and makes the argument for moving to copula random effects models. Our modelling framework is implemented in the package CopulaREMADA within the open source statistical environment R

When is giving an impulse? An ERP investigation of intuitive prosocial behavior

Human prosociality is often assumed to emerge from exerting reflective control over initial, selfish impulses. However, recent findings suggest that prosocial actions can also stem from processes that are fast, automatic and intuitive. Here, we attempt to clarify when prosocial behavior may be intuitive by examining prosociality as a form of reward seeking. Using event-related potentials (ERPs), we explored whether a neural signature that rapidly encodes the motivational salience of an event\u2014the P300\u2014can predict intuitive prosocial motivation. Participants allocated varying amounts of money between themselves and charities they initially labelled as high- or low-empathy targets under conditions that promoted intuitive or reflective decision making. Consistent with our predictions, P300 amplitude over centroparietal regions was greater when giving involved high-empathy targets than low-empathy targets, but only when deciding under intuitive conditions. Reflective conditions, alternatively, elicited an earlier frontocentral positivity related to response inhibition, regardless of target. Our findings suggest that during prosocial decision making, larger P300 amplitude could (i) signal intuitive prosocial motivation and (ii) predict subsequent engagement in prosocial behavior. This work offers novel insight into when prosociality may be driven by intuitive processes and the roots of such behaviors

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa

A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence

A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality

Hybrid copula mixed models for combining case-control and cohort studies in meta-analysis of diagnostic tests

Copula mixed models for trivariate (or bivariate) meta-analysis of diagnostic test accuracy studies accounting (or not) for disease prevalence have been proposed in the biostatistics literature to synthesize information. However, many systematic reviews often include case-control and cohort studies, so one can either focus on the bivariate meta-analysis of the case-control studies or the trivariate meta-analysis of the cohort studies, as only the latter contains information on disease prevalence. In order to remedy this situation of wasting data we propose a hybrid copula mixed model via a combination of the bivariate and trivariate copula mixed model for the data from the case-control studies and cohort studies, respectively. Hence, this hybrid model can account for study design and also due to its generality can deal with dependence in the joint tails. We apply the proposed hybrid copula mixed model to a review of the performance of contemporary diagnostic imaging modalities for detecting metastases in patients with melanoma

Quasi-static imaged-based immersed boundary-finite element model of human left ventricle in diastole

SUMMARY: Finite stress and strain analyses of the heart provide insight into the biomechanics of myocardial function and dysfunction. Herein, we describe progress toward dynamic patient-specific models of the left ventricle using an immersed boundary (IB) method with a finite element (FE) structural mechanics model. We use a structure-based hyperelastic strain-energy function to describe the passive mechanics of the ventricular myocardium, a realistic anatomical geometry reconstructed from clinical magnetic resonance images of a healthy human heart, and a rule-based fiber architecture. Numerical predictions of this IB/FE model are compared with results obtained by a commercial FE solver. We demonstrate that the IB/FE model yields results that are in good agreement with those of the conventional FE model under diastolic loading conditions, and the predictions of the LV model using either numerical method are shown to be consistent with previous computational and experimental data. These results are among the first to analyze the stress and strain predictions of IB models of ventricular mechanics, and they serve both to verify the IB/FE simulation framework and to validate the IB/FE model. Moreover, this work represents an important step toward using such models for fully dynamic fluid–structure interaction simulations of the heart

Improving understanding of the functional diversity of fisheries by exploring the influence of global catch reconstruction

Functional diversity is thought to enhance ecosystem resilience, driving research focused on trends in the functional composition of fisheries, most recently with new reconstructions of global catch data. However, there is currently little understanding of how accounting for unreported catches (e.g. small-scale and illegal fisheries, bycatch and discards) influences functional diversity trends in global fisheries. We explored how diversity estimates varied among reported and unreported components of catch in 2010, and found these components had distinct functional fingerprints. Incorporating unreported catches had little impact on global-scale functional diversity patterns. However, at smaller, management-relevant scales, the effects of incorporating unreported catches were large (changes in functional diversity of up to 46%). Our results suggest there is greater uncertainty about the risks to ecosystem integrity and resilience from current fishing patterns than previously recognized. We provide recommendations and suggest a research agenda to improve future assessments of functional diversity of global fisheries

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Long-term exposure to environmental concentrations of the pharmaceutical ethynylestradiol causes reproductive failure in fish

International audienceHeightened concern over endocrine-disrupting chemicals is driven by the hypothesis that they could reduce reproductive success and affect wildlife populations, but there is little evidence for this expectation. The pharmaceutical ethynylestradiol (EE(2)) is a potent endocrine modulator and is present in the aquatic environment at biologically active concentrations. To investigate impacts on reproductive success and mechanisms of disruption, we exposed breeding populations (n = 12) of zebrafish (Danio rerio) over multiple generations to environmentally relevant concentrations of EE(2). Life-long exposure to 5 ng/L EE(2) in the F, generation caused a 56% reduction in fecundity and complete population failure with no fertilization. Conversely, the same level of exposure for up to 40 days in mature adults in the parental F(0) generation had no impact on reproductive success. Infertility in the F, generation after life-long exposure to 5 ng/L EE(2) was due to disturbed sexual differentiation, with males having no functional testes and either undifferentiated or intersex gonads. These F, males also showed a reduced vitellogenic response when compared with F(0) males, indicating an acclimation to EE(2) exposure. Deputation studies found only a partial recovery in reproductive capacity after 5 months. Significantly, even though the F(0) males lacked functional testes, they showed male-pattern reproductive behavior, inducing the spawning act and competing with healthy males to disrupt fertilization. Endocrine disruption is therefore likely to affect breeding dynamics and reproductive success in group-spawning fish. Our findings raise major concerns about the population-level impacts for wildlife of long-term exposure to low concentrations of estrogenic endocrine disruptors

An essential role for decorin in bladder cancer invasiveness

Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours.Fil: El Behi, Mohamed. Institute Curie; Francia. Centre de Recherche de I; Francia. Inserm; FranciaFil: Krumeich, Sophie. Institute Curie; Francia. Inserm; FranciaFil: Lodillinsky, Catalina. Institute Curie; Francia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kamoun, Aurélie. Institute Curie; FranciaFil: Tibaldi, Lorenzo. Institute Curie; Francia. Inserm; FranciaFil: Sugano, Gaël. Institute Curie; Francia. Inserm; FranciaFil: de Reynies, Aurélien. Ligue Nationale Contre le Cancer; FranciaFil: Chapeaublanc, Elodie. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Laplanche, Agnès. Centre National de la Recherche Scientifique; Francia. Institut de Cancérologie Gustave Roussy; FranciaFil: Lebret, Thierry. Hôpital Foch. Service d; Francia. Université de Versailles; FranciaFil: Allory, Yves. Inserm; FranciaFil: Radvanyi, François. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lantz, Olivier. Institute Curie; Francia. Inserm; FranciaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernard Pierrot, Isabelle. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Théery, Clotilde. Institute Curie; Francia. Inserm; Franci