A Bayesian Joint Model for Compositional Mediation Effect Selection in Microbiome Data

Analyzing multivariate count data generated by high-throughput sequencing technology in microbiome research studies is challenging due to the high-dimensional and compositional structure of the data and overdispersion. In practice, researchers are often interested in investigating how the microbiome may mediate the relation between an assigned treatment and an observed phenotypic response. Existing approaches designed for compositional mediation analysis are unable to simultaneously determine the presence of direct effects, marginal indirect effects, overall indirect effects, as well potential confounders, while simultaneously quantifying their uncertainty. We propose a formulation of a Bayesian joint model for compositional data that allows for the identification, estimation, and uncertainty quantification of various causal estimands in high-dimensional mediation analysis. We conduct simulation studies and compare our method's mediation effects selection performance with existing methods. Finally, we apply our method to a benchmark data set investigating the sub-therapeutic antibiotic treatment effect on body weight in early-life mice

Motives to Report Adverse Drug Reactions to the National Agency:A Survey Study among Healthcare Professionals and Patients in Croatia, The Netherlands, and the UK

Introduction Healthcare professionals (HCPs) and patients have various motives to report adverse drug reactions (ADRs) to their national agency. These motives may differ between countries. Objective The aim of this study was to assess to what extent motives of HCPs and patients to report ADRs differ between countries. Methods HCPs and patients from Croatia (HR), The Netherlands (NL), and the UK were asked to complete a web-based survey containing questions regarding demographics and ADR reporting. HCPs and patients could select all motives for reporting that applied to them, with a total of 23 and 24 motives, respectively. Descriptive statistics are presented and Chi-square tests were used to test for differences across the countries, with effect sizes calculated using Cramer's V. Results In total, 296 HCPs and 423 patients were included (60% and 32% from Croatia, 19% and 44% from NL, and 21% and 24% from the UK, respectively). For most of the motives to report or not to report an ADR, there were no differences between countries. Most HCPs from all countries would be motivated to report an ADR if there was a strong suspicion of causality (89%), if it concerned a severe/serious ADR (86%), and if it concerned an ADR for a new, recently marketed drug (77%). Most patients from all countries agreed that they would report an ADR if it concerned a severe ADR (96%), if the ADR influenced their daily activities (91%), and if they were worried about their own situation (90%). Differences across the countries (p V &gt;= 0.21) were observed for three and four of the HCP and patient motives, respectively. For HCPs, these differences were seen in motives related to legal obligation (65% HR, 24% NL, 38% UK), black triangle medicines (27% HR, 4% NL, 77% UK), and the reporting of well-known ADRs (53% HR, 85% NL, 69% UK). For patients, these differences were seen in motives related to a linkage between the ADR report and the medical notes (59% HR, 60% NL, 30% UK), complexity and time taken to report (25% HR, 13% NL, 40% UK), medicines purchased on the internet (59% HR, 39% NL, 65% UK), and the reporting of embarrassing ADRs (32% HR, 11% NL, 35% UK). Conclusions HCPs' and patients' motives to report or not to report ADRs to the national agency were mostly similar across the three countries. Such motives can be used in general strategies to promote and increase ADR reporting. The observed differences provide guidance to further fine-tune ADR reporting at a national level.</p

The development of METAL-WRF Regional Model for the description of dust mineralogy in the atmosphere

The mineralogical composition of airborne dust particles is an important but often neglected parameter for several physiochemical processes, such as atmospheric radiative transfer and ocean biochemistry. We present the development of the METAL-WRF module for the simulation of the composition of desert dust minerals in atmospheric aerosols. The new development is based on the GOCART-AFWA dust module of WRF-Chem. A new wet deposition scheme has been implemented in the dust module alongside the existing dry deposition scheme. The new model includes separate prognostic fields for nine (9) minerals: illite, kaolinite, smectite, calcite, quartz, feldspar, hematite, gypsum, and phosphorus, derived from the GMINER30 database and also iron derived from the FERRUM30 database. Two regional model sensitivity studies are presented for dust events that occurred in August and December 2017, which include a comparison of the model versus elemental dust composition measurements performed in the North Atlantic (at Izaña Observatory, Tenerife Island) and in the eastern Mediterranean (at Agia Marina Xyliatos station, Cyprus Island). The results indicate the important role of dust minerals, as dominant aerosols, for the greater region of North Africa, South Europe, the North Atlantic, and the Middle East, including the dry and wet depositions away from desert sources. Overall, METAL-WRF was found to be capable of reproducing the relative abundances of the different dust minerals in the atmosphere. In particular, the concentration of iron (Fe), which is an important element for ocean biochemistry and solar absorption, was modeled in good agreement with the corresponding measurements at Izaña Observatory (22% overestimation) and at Agia Marina Xyliatos site (4% overestimation). Further model developments, including the implementation of newer surface mineralogical datasets, e.g., from the NASA-EMIT satellite mission, can be implemented in the model to improve its accuracy.This study was supported by the Hellenic Foundation for Research and Innovation project Mineralogy of Dust Emissions and Impacts on Environment and Health (MegDeth - HFRI no. 703). Part of this study was conducted within the framing of the AERO-EXTREME (PID2021-125669NB-I00) project funded by the State Research Agency/Agencia Estatal de Investigación of Spain and the European Regional Development Funds

The MEDEA childhood asthma study design for mitigation of desert dust health effects: implementation of novel methods for assessment of air pollution exposure and lessons learned

Background: Desert dust events in Mediterranean countries, originating mostly from the Sahara and Arabian deserts, have been linked to climate change and are associated with significant increase in mortality and hospital admissions from respiratory causes. The MEDEA clinical intervention study in children with asthma is funded by EU LIFE+ program to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related health effects. Methods: This paper describes the design, methods, and challenges of the MEDEA childhood asthma study, which is performed in two highly exposed regions of the Eastern Mediterranean: Cyprus and Greece-Crete. Eligible children are recruited using screening surveys performed at primary schools and are randomized to three parallel intervention groups: a) no intervention for desert dust events, b) interventions for outdoor exposure reduction, and c) interventions for both outdoor and indoor exposure reduction. At baseline visits, participants are enrolled on MEDena® Health-Hub, which communicates, alerts and provides exposure reduction recommendations in anticipation of desert dust events. MEDEA employs novel environmental epidemiology and telemedicine methods including wearable GPS, actigraphy, health parameters sensors as well as indoor and outdoor air pollution samplers to assess study participants’ compliance to recommendations, air pollutant exposures in homes and schools, and disease related clinical outcomes. Discussion: The MEDEA study evaluates, for the first time, interventions aiming to reduce desert dust exposure and implement novel telemedicine methods in assessing clinical outcomes and personal compliance to recommendations. In Cyprus and Crete, during the first study period (February–May 2019), a total of 91 children participated in the trial while for the second study period (February–May 2020), another 120 children completed data collection. Recruitment for the third study period (February–May 2021) is underway. In this paper, we also present the unique challenges faced during the implementation of novel methodologies to reduce air pollution exposure in children. Engagement of families of asthmatic children, schools and local communities, is critical. Successful study completion will provide the knowledge for informed decision-making both at national and international level for mitigating the health effects of desert dust events in South-Eastern Europe. Trial registration: ClinicalTrials.gov: NCT03503812, April 20, 2018

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

ReviewHuman biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.Supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032]info:eu-repo/semantics/publishedVersio

A systematic approach synergizing toxicological and epidemiological knowledge

Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032 ]. Authors acknowledge the editorial assistance of Richard Davies. Publisher Copyright: © 2023 The Author(s)Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.publishersversionpublishe

Pathway using WUDAPT's Digital Synthetic City tool towards generating urban canopy parameters for multi-scale urban atmospheric modeling

The WUDAPT (World Urban Database and Access Portal Tools project goal is to capture consistent information on urban form and function for cities worldwide that can support urban weather, climate, hydrology and air quality modeling. These data are provided as urban canopy parameters (UCPs) as used by weather, climate and air quality models to simulate the effects of urban surfaces on the overlying atmosphere. Information is stored with different levels of detail (LOD). With higher LOD greater spatial precision is provided. At the lowest LOD, Local Climate Zones(LCZ) with nominal UCP ranges is provided (order 100 m or more). To describe the spatial heterogeneity present in cities with great specificity at different urban scales we introduce the Digital Synthetic City (DSC) tool to generate UCPs at any desired scale meeting the fit-for-purpose goal of WUDAPT. 3D building and road elements of entire city landscapes are simulated based on readily available data. Comparisons with real-world urban data are very encouraging. It is customized (C-DSC) to incorporate each city's unique building morphologies based on unique types, variations and spatial distribution of building typologies, architecture features, construction materials and distribution of green and pervious surfaces. The C-DSC uses crowdsourcing methods and sampling within city Testbeds from around the world. UCP data can be computed from synthetic images at selected grid sizes and stored such that the coded string provides UCP values for individual grid cells

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec