Support Risk Assessment Research Articles

Developing quantitative Adverse Outcome Pathways: An ordinary differential equation-based computational framework

The Adverse Outcome Pathway (AOP) biological framework was introduced in 2012, yet defining a mathematical/computational framework for quantitative AOP (qAOP) development remains an open problem. In order to properly unravel the intricate biological mechanisms described by AOPs and provide quantitative predictions to support risk assessment, a computational model should provide a clear time-course prediction of key events (KEs), as well as describe the key event relationships (KERs) linking a molecular initiating event (MIE) to an adverse outcome (AO). Ultimately, the mathematical description of those links entails the possibility of quantitatively predicting adverse effects based on early events.Here, we propose an ordinary differential equation (ODE) - based qAOP framework, as ODEs provide a time-course description of KEs and KERs. We illustrate how the application of computational techniques, such as Bayesian inference and Leave-one-out cross-validation (LOO-CV), can assist AOP development, introducing concepts of qAOP model selection and qAOP updating. Furthermore, we compare ODE and response–response based qAOP models, showing that ODE-based qAOPs can avoid erroneous predictions potentially resulting from response–response qAOPs. Finally, we show how ODE parameter variability can be linked to AO variability across a population. Overall, this framework serves as a valuable mathematical and computational tool for the development of qAOP models, enhancing our comprehension of intricate biological pathways associated with adverse outcomes.

Characterization of individuals with atherosclerotic cardiovascular disease, with and without chronic kidney disease: results from a UK electronic health record database

Abstract Introduction Elevated C-reactive protein (CRP) levels are often present in individuals with atherosclerotic cardiovascular disease (ASCVD), including in those who also have chronic kidney disease (CKD), and are associated with an increased risk of major adverse cardiovascular events (MACE). To understand unmet needs in the identification and management of at-risk individuals, we characterized patients with ASCVD in a UK database, according to CKD stage and CRP levels. Methods This study comprised separate retrospective cross-sectional and longitudinal cohort analyses of patients in the Clinical Practice Research Datalink (CPRD) Aurum database, a representative UK database of anonymized primary care records. In the cross-sectional analysis, CPRD Aurum was linked with Hospital Episode Statistics (HES) and Index of Multiple Deprivation data to assess patient characteristics on 1 Jan 2021 (defined as index date). In the cohort analysis, CPRD Aurum was linked with HES and Office for National Statistics mortality data to determine the incidence of 3-point MACE (3P-MACE) over approximately 5 years of follow-up (index date: 1 Jan 2016). Both analyses included individuals ≥ 18 years old with an ASCVD diagnosis in both primary and secondary care in the 5 years pre-index. Data were analysed using descriptive statistics. Patient characteristics were assessed by CKD stage; for individuals with CKD stage 3–4, characteristics were also assessed by CRP levels. Results In total, 225,767 and 230,055 individuals were included in the cross-sectional and cohort analyses, respectively. The prevalence of CKD stage 3–4 among individuals with ASCVD was 24.3% (Table 1). The proportion of individuals with elevated CRP (CRP ≥ 2 mg/L) and anaemia increased for successively higher CKD severity groups; in addition, glycated haemoglobin (HbA1c) ≥ 7% and elevated blood pressure were generally more frequently observed in individuals with CKD than in those without (Table 1). Individuals with ASCVD, CKD stage 3–4 and elevated CRP had higher HbA1c and total cholesterol levels and a greater proportion had obesity, anaemia and elevated blood pressure, compared with individuals with CRP < 2 mg/L (Table 2). Over 5 years’ follow-up, the incidence of 3P-MACE increased with CKD severity (Table 1) and with increasing CRP levels in individuals with ASCVD and CKD stage 3–4 (Table 2). However, only 28% of individuals with ASCVD and CKD stage 3–4 had CRP measurements. Conclusion Adults with ASCVD, CKD and elevated CRP identified from primary and secondary UK care records had a higher disease burden than individuals with CRP levels < 2 mg/L. In the UK, testing CRP levels is not routinely recommended, resulting in a high proportion of missing CRP measurements in this study. Routine testing of CRP may help in identifying patients with residual cardiovascular risk and has the potential to support risk assessment and management of patients with ASCVD and CKD.

AOP Report: Development of an adverse outcome pathway for deposition of energy leading to bone loss.

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has also been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms are well documented but the causal connectivity of events to bone loss development remains incompletely understood. Herein, the adverse outcome pathway (AOP) framework was used to organize data and develop a qualitative AOP beginning from deposition of energy (the molecular initiating event) to bone loss (the adverse outcome). This qualitative AOP was developed in collaboration with bone loss research experts to aggregate relevant findings, supporting ongoing efforts to understand and mitigate human system risks associated with radiation exposures. A literature review was conducted to compile and evaluate the state of knowledge based on the modified Bradford Hill criteria. Following review of 2029 studies, an empirically supported AOP was developed, showing the progression to bone loss through many factors affecting the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The structural, functional, and quantitative basis of each proposed relationship was defined, for inference of causal changes between key events. Current knowledge and its gaps relating to dose-, time- and incidence-concordance across the key events were identified, as well as modulating factors that influence linkages. The new priorities for research informed by the AOP highlight areas for improvement to enable development of a quantitative AOP used to support risk assessment strategies for space travel or cancer radiotherapy.

Can genomics and meteorology predict outbreaks of legionellosis in urban settings?

Legionella pneumophila is ubiquitous and sporadically infects humans causing Legionnaire's disease (LD). Globally, reported cases of LD have risen fourfold from 2000 to 2014. In 2016, Sydney, Australia was the epicenter of an outbreak caused by L. pneumophila serogroup 1 (Lpsg1). Whole-genome sequencing was instrumental in identifying the causal clone which was found in multiple locations across the city. This study examined the epidemiology of Lpsg1 in an urban environment, assessed typing schemes to classify resident clones, and investigated the association between local climate variables and LD outbreaks. Of 223 local Lpsg1 isolates, we identified dominant clones with one clone isolated from patients in high frequency during outbreak investigations. The core genome multi-locus sequence typing scheme was the most reliable in identifying this Lpsg1 clone. While an increase in humidity and rainfall was found to coincide with a rise in LD cases, the incidence of the major L. pneumophila outbreak clone did not link to weather phenomena. These findings demonstrated the role of high-resolution typing and weather context assessment in determining source attribution for LD outbreaks in urban settings, particularly when clinical isolates remain scarce.IMPORTANCEWe investigated the genomic and meteorological influences of infections caused by Legionella pneumophila in Sydney, Australia. Our study contributes to a knowledge gap of factors that drive outbreaks of legionellosis compared to sporadic infections in urban settings. In such cases, clinical isolates can be rare, and thus, other data are needed to inform decision-making around control measures. The study revealed that core genome multi-locus sequence typing is a reliable and adaptable technique when investigating Lpsg1 outbreaks. In Sydney, the genomic profile of Lpsg1 was dominated by a single clone, which was linked to numerous community cases over a period of 40 years. Interestingly, the peak in legionellosis cases during Autumn was not associated with this prevalent outbreak clone. Incorporating meteorological data with Lpsg1 genomics can support risk assessment strategies for legionellosis in urban environments, and this approach may be relevant for other densely populated regions globally.

Detection of tomato brown rugose fruit virus in environmental residues: The importance of contextualizing test results

AbstractTomato brown rugose fruit virus (ToBRFV) is regulated as a quarantine pest in many countries worldwide. To assess whether ToBRFV is present in cultivations, plants or seed lots, testing is required. The interpretation of test results, however, can be challenging. Reverse transcription‐quantitative (real‐time) PCR results, even though considered “positive”, may not always signify plant infection or indicate the presence of infectious virus, but could be due to the presence of viral residues in the environment. Here, case studies from the Netherlands, Belgium, and the United Kingdom address questions regarding the detection of ToBRFV in various settings, and the infectiousness of ToBRFV‐positive samples. These exploratory analyses demonstrate widespread detection of ToBRFV in diverse samples and environments. ToBRFV was detected inside and around greenhouses with no prior history of ToBRFV infection, and on different materials and surfaces, including those that were untouched by individuals, plants or objects. This suggested the dispersal of viral residues through aerosols. ToBRFV or its residues were more often detected in regions with nearby tomato production, yet were also found in a wider environment extending beyond infected crops. ToBRFV originating from environmental contamination may or may not be infectious, adding complexity to decision‐making in response to positive test results. Contextual information, such as the origin of the sample and the likelihood of residues from prior cultivations and/or the broader environment, is important for interpreting test results. A nuanced approach is crucial to correctly interpret ToBRFV test results, necessitating further research to support risk assessment.

Advancing PFAS risk assessment: Integrative approaches using agent-based modelling and physiologically-based kinetic for environmental and health safety

Per- and polyfluoroalkyl substances (PFAS), ubiquitous in a myriad of consumer and industrial products, and depending on the doses of exposure represent a hazard to both environmental and public health, owing to their persistent, mobile, and bio accumulative properties. These substances exhibit long half-lives in humans and can induce potential immunotoxic effects at low exposure levels, sparking growing concerns. While the European Food Safety Authority (EFSA) has assessed the risk to human health related to the presence of PFAS in food, in which a reduced antibody response to vaccination in infants was considered as the most critical human health effect, a comprehensive grasp of the molecular mechanisms spearheading PFAS-induced immunotoxicity is yet to be attained. Leveraging modern computational tools, including the Agent-Based Model (ABM) Universal Immune System Simulator (UISS) and Physiologically Based Kinetic (PBK) models, a deeper insight into the complex mechanisms of PFAS was sought. The adapted UISS serves as a vital tool in chemical risk assessments, simulating the host immune system's reactions to diverse stimuli and monitoring biological entities within specific adverse health contexts. In tandem, PBK models unravelling PFAS' biokinetics within the body i.e. absorption, distribution, metabolism, and elimination, facilitating the development of time-concentration profiles from birth to 75 years at varied dosage levels, thereby enhancing UISS-TOX's predictive abilities. The integrated use of these computational frameworks shows promises in leveraging new scientific evidence to support risk assessments of PFAS. This innovative approach not only allowed to bridge existing data gaps but also unveiled complex mechanisms and the identification of unanticipated dynamics, potentially guiding more informed risk assessments, regulatory decisions, and associated risk mitigations measures for the future.

A Framework for a Hazard Taxonomy to Support Risk Assessment of Tangible Outdoor Heritage

The variety of hazards with a potential impact on cultural heritage requires a multidisciplinary approach and a preliminary overview of the existing methods for risk assessment in order to define a comprehensive hazard taxonomy. The starting point of the research thus aims to build a multidisciplinary framework to support the risk assessment process according to the classification of cultural heritage based on the harmonization of European vocabularies’ definitions and protocols. To collect the necessary information, such as hazard classification, indicators, indices and thresholds, a series of methodologies was adopted: analysis of the main international protocols and the EU Research projects related to risk assessment in cultural heritage, expert-based knowledge and a systematic literature review. The research aims to fill a gap in the field of quantitative and indicator-based risk assessment that does not present a unique and all-encompassing framework capable of collecting the main natural and anthropic risks along with the related taxonomy in a single repository. The framework has been set up to be consulted by researchers, professionals and public administrations to support the evaluation process of potential risks on tangible outdoor heritage enabling users to incrementally add exposure and vulnerability data for each specific risk.

GWPD: a multifunctional platform to unravel biological risk factors in global engineered water systems

Engineered water systems such as wastewater treatment plants (WWTPs) are potential reservoirs of various biological risk factors (BRFs), including pathogens, antibiotic resistance genes (ARGs), and virulence factors (VFs). Currently, a BRF database relevant to engineered water systems on a global geographic scale is lacking. Here, we present the Global Wastewater Pathogen Database (GWPD, http://gwpd.hitsz.edu.cn), an online database that provides information on the diversity, abundance, and distribution of BRFs from 1302 metagenome samples obtained from 186 cities, 68 countries, and six continents. We sorted these samples into six types: sewer networks, influent, anoxic activated sludge, oxic activated sludge, effluent, and receiving/natural waters. In total, 476 pathogens, 442 ARGs, and 246 VFs were identified. As a multifunctional database, GWPD provides an interactive visualization of these BRFs in a world map, an information retrieval interface, and an online one-click service for BRF annotation from metagenome sequencing data. GWPD is built on a web service framework, which can be readily extended to future versions of GWPD by adding more functional modules and connecting to other data sources, such as epidemic databases, to support risk assessment and control in the context of “One Health.”

A novel bioaccessibility prediction method for complex petroleum hydrocarbon mixtures in soil.

More evidence shows that bioaccessibility instead of total concentrations based on exhaustive extraction methods can better reflect the actual risk level of petroleum hydrocarbon contaminated sites, so it is essential to establish an effective assessment method for bioaccessibility. This study utilized Tenax extraction, butanol extraction, hydroxypropyl-β-cyclodextrin (HPCD) extraction, and a composite extraction method involving HPCD with LMWOAs (citric acid, CA) and surfactants (rhamnolipid, RL; Tween80, TW80; sodium dodecyl sulfate, SDS) at varying concentrations. These methods were employed to predict the bioaccessibility of earthworms to soil at different aging time of petroleum hydrocarbons. The results showed that traditional extraction methods such as Tenax 6h extraction and n-butanol extraction were ineffective in evaluating petroleum hydrocarbons' bioaccessibility. In contrast, the composite extraction of HPCD and solubilizer enhanced the extraction efficiency of HPCD greatly, and the extraction results showed a significant positive correlation with earthworm accumulation. By the comparison of the extraction results of different fractions of petroleum hydrocarbons, heavy fractions of petroleum hydrocarbons (C29-C40) are essential factors affecting chemical extraction effects. The correlation coefficients of four composite extraction methods and total petroleum hydrocarbons (TPH) of earthworm accumulation by linear regression analysis ranged from 1.1797 to 1.7990, and the slopes ranged from 0.8727 to 0.9792. Among them, the combined extraction method of 50 mmol/L HPCD and 0.5 mmol/L rhamnolipid had the best effect (r2 = 0.9792, slope = 1.1797), which could be used as an evaluation method suitable for the bioaccessibility of petroleum hydrocarbons in soil. This study could provide a new method for evaluating the bioaccessibility of organic pollutants and technically supporting risk assessment and bioremediation of complex petroleum hydrocarbons in soil.

Cardio-oncology rehabilitation: are we ready?

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an 'exercise only' programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey. The aim of this paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients but also for oncologists, primary care providers, patients, and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during, and after cancer treatment, in order to improve quality of life and to fight health inequities.

COVID-19 cluster surveillance using exposure data collected from routine contact tracing: The genomic validation of a novel informatics-based approach to outbreak detection in England.

Contact tracing was used globally to prevent onwards transmission of COVID-19. Tracing contacts alone is unlikely to be sufficient in controlling community transmission, due to the pre-symptomatic, overdispersed and airborne nature of COVID-19 transmission. We describe and demonstrate the validity of a national enhanced contact tracing programme for COVID-19 cluster surveillance in England. Data on cases occurring between October 2020 and September 2021 were extracted from the national contact tracing system. Exposure clusters were identified algorithmically by matching ≥2 cases attending the same event, identified by matching postcode and event category within a 7-day rolling window. Genetic validity was defined as exposure clusters with ≥2 cases from different households with identical viral sequences. Exposure clusters were fuzzy matched to the national incident management system (HPZone) by postcode and setting description. Multivariable logistic regression modelling was used to determine cluster characteristics associated with genetic validity. Over a quarter of a million (269,470) exposure clusters were identified. Of the eligible clusters, 25% (3,306/13,008) were genetically valid. 81% (2684/3306) of these were not recorded on HPZone and were identified on average of one day earlier than incidents recorded on HPZone. Multivariable analysis demonstrated that exposure clusters occurring in workplaces (aOR = 5·10, 95% CI 4·23-6·17) and education (aOR = 3·72, 95% CI 3·08-4·49) settings were those most strongly associated with genetic validity. Cluster surveillance using enhanced contact tracing in England was a timely, comprehensive and systematic approach to the detection of transmission events occurring in community settings. Cluster surveillance can provide intelligence to stakeholders to support the assessment and management of clusters of COVID-19 at a local, regional, and national level. Future systems should include predictive modelling and network analysis to support risk assessment of exposure clusters to improve the effectiveness of enhanced contract tracing for outbreak detection.

0977 A Non-Pharmacological Insomnia Treatment for Suicidal Behavior in High-Risk Civilians: An Open-Label Clinical Trial

Abstract Introduction Suicide has emerged as a public health crisis, where interventions remain scarce, unacceptable, and inaccessible to those high in need. By comparison, poor sleep is non-stigmatizing, visible, and highly treatable as a risk factor and transdiagnostic intervention target in suicide prevention. Aim 1: To develop, manualize, and test feasibility of a sleep-oriented treatment for suicidal behaviors within an open label clinical trial. Aim 2: To test antisuicidal response and indications of efficacy posttreatment across primary (suicidal ideation), secondary (sleep indices), and exploratory (mood indices) outcomes. Methods A multicomponent selective treatment was developed integrating: CBT for Insomnia (CBTi), Imagery Rehearsal Treatment (IRT), and Social Rythyms Treatment (SRT) (to address insomnia, nightmares, sleep variability) within an abbreviated (5-session) format (iSleep: Insomnia Treatment for Improved Well-Being). Treatment was manualized across session-by-session materials (powerpoints, homework, therapist guidesheets). Participants were enrolled based on screening and inclusion criteria: (a) age >18, (b) clinically-significant sleep disturbance (Insomnia Severity Index (ISI>10)); Pittsburgh Sleep Quality Index (PSQI>5)), (c) DSM-V-Defined Major Depressive Disorder, (d) current suicidal ideation (Columbia Suicidal Severity Rating Scale (CSSRS>1)). Comprehensive data and safety monitoring procedures were used to support risk assessment, triage, and outpatient safety planning. Outcomes were assessed at Baseline, Treatment, and Posttreatment (1,3 mos) timepoints. Results Of n=590 new contacts, n=310 participants were screened for high suicide risk. Fifty-nine participants were interviewed by full-battery eligibility assessment, resulting in n=35 participants enrolled for treatment allocation. Feasibility analyses demonstrated high rates of acceptance, tolerability, and safety. Paired t-tests revealed large posttreatment reductions in suicidal ideation (CSSRS, p<.001), in addition to secondary outcomes of sleep disturbance (ISI, p<.001; DDNSI, p<.001) and depression (QIDS-SR, p<.001). Effects were large and sustained through study follow up. Conclusion A non-pharmacological insomnia intervention (iSleep Treatment) resulted in antisuicidal symptom response and posttreatment improvements in sleep and overall well-being. Effects were large and observed across primary, secondary, and exploratory outcomes. This is the first known report testing use of a newly-developed, multicomponent insomnia treatment within an open label suicide prevention clinical trial, demonstrating excellent feasibility, safety, and therapeutic impact to suicidal risk. Support (if any) Work was supported by NIH (K23MH093490) and DOD/MOMRP/MSRC funding (W81XWH-10-2-0178)

The Transformasi Proses Bisnis Produk Asuransi Rangka Kapal di Reasuransi PT. ABC

This research aims to (1) analyze the ongoing H&M insurance business process, (2) identify the root of the problems that hinder the effectiveness of the business process, (3) evaluate underwriting parameters, and (4) design a new business model in PT reinsurance. A B C. The research method used is qualitative analysis involving the Delphi method of seven H&M insurance industry experts who were chosen deliberately. The business model is explained through the Business Process Model and Notation (BPMN). Business process analysis is carried out using root-cause analysis, value-added analysis, waste analysis, and direct weighting analysis to determine the relevance of underwriting parameters. Business transformation is carried out by (1) adding significant risk parameters in the underwriting process, (2) eliminating activities that do not provide added value, (3) increasing risk analysis activities that provide added value to the business acceptance process (underwriting), (4) improving data management through optimizing administration as a data bank and system agent, and (5) implementing pricing rates to maintain stability of rates and premiums. Statistical analysis supports risk assessment and pricing rates to ensure adequate premiums required for further research. In conclusion, a holistic business process transformation accompanied by improved risk analysis and data management is needed to increase the profitability and sustainability of the ship hull insurance industry. Keywords: Ship Hull Insurance, Business Process Management, Business Process Model and Notation (BPMN), Business Process Transformation

Architecture and Development Framework for a Web-Based Risk Assessment and Management Platform Developed on WordPress to Address Opioid Overdose.

The number of overdose-related fatalities continues to reach historic levels across Canada, despite ongoing efforts by authorities. To reduce mortality, a clinical trajectory ranging from preventative measures to crisis intervention, skill training to treatment, and risk assessment to risk management needs to be supported. The web-based Risk Assessment and Management Platform (RAMP) was developed to realize this concept and to empower people who use drugs through an integrated tool that allows them to better understand and manage their risk of overdose. This paper outlines the architecture and development of RAMP, which is built on the WordPress platform. WordPress components are mapped onto a 3-tier architecture that consists of presentation, application, and database layers. The architecture facilitates the development of a modular software that includes several features that are independent in functionality but interact with each other in an integrated platform. The relatively low coupling and high coherence of the features may reduce the cost of maintenance and increase flexibility of future developments. RAMP's architecture comprises a user interface, conceptual framework, and backend layers. The RAMP front end effectively uses some of the WordPress' features such as HTML5, CSS, and JavaScript to create a mobile, friendly, and scalable user interface. The RAMP backend uses several standard and custom WordPress plug-ins to support risk assessment and monitoring, with the goal of mitigating the impacts and eliminating risks together. A rule-based decision support system has been hard-coded to suggest relevant modules and goals to complement each user's lifestyle and goals based on their risk assessment. Finally, the backend uses the MySQL database management system and communicates with the RAMP framework layer via the data access layer to facilitate a timely and secure handling of information. Overall, RAMP is a modular system developed to identify and manage the risk of opioid overdose in the population of people who use drugs. Its modular design uses the WordPress architecture to efficiently communicate between layers and provide a base for external plug-ins. There is potential for the current system to adopt and address other related fields such as suicide, anxiety, and trauma. Broader implementation will support this concept and lead to the next level of functionality.

PBPK modeling to support risk assessment of pyrethroid exposure in French pregnant women

BackgroundPyrethroids are widely used pesticides and are suspected to affect children's neurodevelopment. The characterization of pyrethroid exposure during critical windows of development, such as fetal development and prenatal life, is essential to ensure a better understanding of pyrethroids potential effects within the concept of Developmental Origins of Health and Disease. ObjectiveThe aim of this study was to estimate maternal exposure of French pregnant women from biomonitoring data and simulate maternal and fetal internal concentrations of 3 pyrethroids (permethrin, cypermethrin and deltamethrin) using a multi-substance pregnancy-PBPK (physiologically based pharmacokinetics) model. The estimated maternal exposures were compared to newly proposed toxicological reference values (TRV) children specific also called draft child-specific reference value to assess pyrethroid exposure risk during pregnancy i.e. during the in utero exposure period. MethodsA pregnancy-PBPK model was developed based on an existing adult pyrethroids model. The maternal exposure to each parent compound of pregnant women of the Elfe (French Longitudinal Study since Childhood) cohort was estimated by reverse dosimetry based on urinary biomonitoring data. To identify permethrin and cypermethrin contribution to their common urinary biomarkers of exposure, an exposure ratio based on biomarkers in hair was tested. Finally, exposure estimates were compared to current and draft child-specific reference values derived from rodent prenatal and postnatal exposure studies. ResultsThe main contributor to maternal pyrethroid diet intake is cis-permethrin. In blood, total internal concentrations main contributor is deltamethrin. In brain, the major contributors to internal pyrethroid exposure are deltamethrin for fetuses and cis-permethrin for mothers. Risk is identified only for permethrin when referring to the draft child-specific reference value. 2.5% of the population exceeded permethrin draft child-specific reference value. ConclusionsA new reverse dosimetry approach using PBPK model combined with human biomonitoring data in urine and hair was proposed to estimate Elfe pregnant population exposure to a pyrethroids mixture with common metabolites.

Lessons learned and recommendations from analysis of hydrogen incidents and accidents to support risk assessment for the hydrogen economy

This study addresses challenges associated with hydrogen's physio-chemical characteristics and the need for safety and public acceptance as a precursor to the emerging hydrogen economy. It highlights the gap in existing literature regarding lessons learned from events in the green hydrogen production value chain. The study aims to use the documented lessons learned from previous hydrogen-related events to assist in enhancing safety measures and to guide stakeholders on how to avoid and mitigate future hydrogen-related events. Given the potential catastrophic consequences, robust safety systems are essential for hydrogen economy development. The work underscores the importance of human and operational factors as root causes of these events. The paper recommends establishing a specialized hydrogen-related event database to support risk assessment and risk mitigation, thus catering to the growing hydrogen industry's needs, and facilitating quick access to critical information for stakeholders in the private and public sectors.

Development of an exercise therapy referral clinical support tool for patients with osteoporosis at risk for falls.

The purpose of this study was to develop a clinical support tool for osteoporosis clinic providers to support risk assessment and referrals for evidence-based exercise therapy programs. A sequential Delphi method was used with a multidisciplinary group of national falls experts, to provide consensus on referral to exercise therapy for patients at risk for falls. The Delphi study included a primary research team, expert panel, and clinical partners to answer the questions: (1) "What patient characteristics are needed to develop a clinical support tool?"; (2) "What are the recommended exercise referrals for patients with osteoporosis at risk for falls?" The consensus process consisted of two rounds with 8 weeks between meetings. Two qualitative researchers analyzed the data using a modified version of a matrix analysis approach. The following were the most important variables to include when determining exercise therapy referrals for patients with osteoporosis: Patient history and demographics, falls history over the last year, current physical function and balance, caregiver and transportation status, socioeconomic and insurance status, and patient preference. Potential exercise therapy referrals included one-on-one physical therapy, group physical therapy, home health, community-based exercise programs, and not acceptable for exercise therapy. Patient characteristics including patient history, physical function and balance performance, socioeconomic and insurance status, and patient preference for exercise therapy are important to inform both the medical provider and patient with osteoporosis to choose the most appropriate exercise therapy referral. Adoption of the algorithmic suggestions may have a significant impact on uptake and adherence to exercise therapy, ultimately improving patient physical function and reducing falls risk.

Determination of the binding affinities of OPEs to integrin αvβ3 and elucidation of the underlying mechanisms via a competitive binding assay, pharmacophore modeling, molecular docking and QSAR modeling

Organophosphate esters (OPEs) can cause adverse biological effects through binding to integrin αvβ3. However, few studies have focused on the binding activity and mechanism of OPEs to integrin αvβ3. Herein, a comprehensive investigation of the mechanisms by which OPEs bind to integrin αvβ3 and determination of the binding affinity were conducted by in vitro and in silico approaches: competitive binding assay as well as pharmacophore, molecular docking and QSAR modeling. The results showed that all 18 OPEs exhibited binding activities to integrin αvβ3; moreover, hydrogen bonds were identified as crucial intermolecular interactions. In addition, essential factors, including the −P = O structure of OPEs, key amino acid residues and suitable cavity volume of integrin αvβ3, were identified to contribute to the formation of hydrogen bonds. Moreover, aryl-OPEs exhibited a lower binding activity with integrin αvβ3 than halogenated- and alkyl-OPEs. Ultimately, the QSAR model constructed in this study was effectively used to predict the binding affinity of OPEs to integrin αvβ3, and the results suggest that some OPEs might pose potential risks in aquatic environments. The results of this study comprehensively elucidated the binding mechanism of OPEs to integrin αvβ3, and supported the environmental risk management of these emerging pollutants.

Wearable Stretch Sensors for Ergonomics-Related Human Movement Monitoring

Physical ergonomics has shown to be an effective method of keeping an eye on any illnesses associated with, like, job-related tasks. Wearable sensors and artificial intelligence have been used in conjunction to enhance experimental ergonomic research techniques in the field of physical ergonomics, according to a number of recent studies. This study proposes the Smart Work wear System, a module-based ambulatory system that addresses work-related physical and psychosocial stresses that might impact health and performance. It supports risk assessment, technique training, and workplace design while reducing the requirement for expert trainers and ergonomists. Substituting measurements for observations improves measurement accuracy and repeatability. A modular platform allows for the connection of a variety of sensor types based on the individual requirements of each case.

Baseline characteristics and outcome of stroke patients after endovascular therapy according to previous symptomatic vascular disease and sex.

The aim of this study was to investigate baseline characteristics and outcome of patients after endovascular therapy (EVT) for acute large vessel occlusion (LVO) in relation to their history of symptomatic vascular disease and sex. Consecutive EVT-eligible patients with LVO in the anterior circulation admitted to our stroke center between 04/2015 and 04/2020 were included in this observational cohort study. All patients were treated according to a standardized acute ischaemic stroke (AIS) protocol. Baseline characteristics and successful reperfusion, recurrent/progressive in-hospital ischaemic stroke, symptomatic in-hospital intracranial hemorrhage, death at discharge and at 3 months, and functional outcome at 3 months were analyzed according to previous symptomatic vascular disease and sex. 995 patients with LVO in the anterior circulation (49.4% women, median age 76 years, median admission NIHSS score 14) were included. Patients with multiple vs. no previous vascular events showed higher mortality at discharge (20% vs. 9.3%, age/sex - adjustedOR = 1.43, p = 0.030) and less independency at 3 months (28.8% vs. 48.8%, age/sex - adjustedOR = 0.72, p = 0.020). All patients and men alone with one or multiple vs. patients and men with no previous vascular events showed more recurrent/progressive in-hospital ischaemic strokes (19.9% vs. 6.4% in all patients, age/sex - adjustedOR = 1.76, p = 0.028) (16.7% vs. 5.8% in men, age-adjustedOR = 2.20, p = 0.035). Men vs. women showed more in-hospital symptomatic intracranial hemorrhage among patients with one or multiple vs. no previous vascular events (23.7% vs. 6.6% in men and 15.4% vs. 5.5% in women, OR = 2.32, p = 0.035/age - adjustedOR = 2.36, p = 0.035). Previous vascular events increased the risk of in-hospital complications and poorer outcome in the analyzed patients with EVT-eligible LVO-AIS. Our findings may support risk assessment in these stroke patients and could contribute to the design of future studies.