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Though relatively common, syncope is a complex presenting symptom defined by a transient loss of consciousness, usually accompanied by falling, and with spontaneous recovery. Syncope must be carefully differentiated from other conditions that may cause a loss of consciousness or falling. Syncope can be classified into four categories: reflex mediated, cardiac, orthostatic, and cerebrovascular. A cardiac cause of syncope is associated with significantly higher rates of morbidity and mortality than other causes. The evaluation of syncope begins with a careful history, physical examination, and electrocardiography. Additional testing should be based on the initial clinical evaluation. Older patients and those with underlying organic heart disease or abnormal electrocardiograms generally will need additional cardiac evaluation, which may include prolonged electrocardiographic monitoring, echocardiography, and exercise stress testing. When structural heart disease is excluded, tests for neurogenic reflex-mediated syncope, such as head-up tilt-table testing and carotid sinus massage, should be performed. The use of tests such as head computed tomography, magnetic resonance imaging, carotid and transcranial ultrasonography, and electroencephalography to detect cerebrovascular causes of syncope should be reserved for those few patients with syncope whose history suggests a neurologic event or who have focal neurologic signs or symptoms. [ABSTRACT FROM AUTHOR]

Fifty species of guanophilic (bat guano-loving) fungi were isolated from field-collected samples within three caves in southwesternPuerto Rico; most were mitosporic fungi (23 species). The caves studied were Cueva La Tuna (Cabo Rojo), Cueva de Malano(Sistema de Los Chorros, San Germán), and Cueva Viento (El Convento Cave-Spring System, Guayanilla-Peñuelas). The mostconspicuous fungus by far was the zygomycete Circinella umbellata (Mucorales). Circinella umbellata dominated the bat guanoincubation chambers (Petri dishes lined with sterile filter paper moistened with sterile water) at ambient laboratory conditions.Nineteen species of basidiomycetes (e.g., Ganoderma cf. resinaceum, Geastrum cf. minimum, Lepiota sp., Polyporus sp., Ramariasp.) and three species of ascomycetes (Hypoxylon sp., Xylaria anisopleura, and X. kegeliana) were also recorded. They were foundon soil, rotting leaves, bark and rotting wood, buried in bat guano located below natural skylights or sinkholes.

Dense granular flows exhibit fascinating kinematic patterns characterised by strong fluctuations in grain velocities. In this paper, we analyse these fluctuations and discuss their possible role on macroscopic properties such as effective viscosity, non-locality and shear-induced diffusion. The analysis is based on 2D experimental granular flows performed with the stadium shear device and DEM simulations. We first show that, when subjected to shear, grains self-organised into clusters rotating like rigid bodies. The average size of these so-called granular vortices is found to increase and diverge for lower inertial numbers, when flows decelerate and stop. We then discuss how such a microstructural entity and its associated internal length scale, possibly much larger than a grain, may be used to explain two important properties of dense granular flows: (i) the existence of shear-induced diffusion of grains characterised by a shear-rate independent diffusivity and (ii) the development of boundary layers near walls, where the viscosity is seemingly lower than the viscosity far from walls.

The characteristic X-rays produced by the interactions of the electron beam with the sample in a scanning electron microscope (SEM) are usually captured with a variable-energy detector, a process termed energy dispersive spectrometry (EDS). The purpose of this work is to exploit inverse simulations of SEM-EDS spectra to enable rapid determination of sample properties, particularly elemental composition. This is accomplished using penORNL, a modified version of PENELOPE, and a modified version of the traditional Levenberg–Marquardt nonlinear optimization algorithm, which together is referred to as MOZAIK-SEM. The overall conclusion of this work is that MOZAIK-SEM is a promising method for performing inverse analysis of X-ray spectra generated within a SEM. As this methodology exists now, MOZAIK-SEM has been shown to calculate the elemental composition of an unknown sample within a few percent of the actual composition.

AWE (UK), IRSN (France), LLNL (USA) and ORNL (USA) began a long term collaboration effort in 2015 to update the nuclear criticality Slide Rule for the emergency response to a nuclear criticality accident. This document, published almost 20 years ago, gives order of magnitude estimates of key parameters, such as number of fissions and doses (neutron and gamma), useful for emergency response teams and public authorities. This paper will present, firstly the motivation and the long term objectives for this update, then the overview of the initial configurations for updated calculations and preliminary results obtained with modern 3D codes.

Abstract Background Disparities in outcomes associated with race and ethnicity are well documented for many diseases and patient populations. Tuberculosis (TB) disproportionately affects economically disadvantaged, racial and ethnic minority populations. Pulmonary impairment after tuberculosis (PIAT) contributes heavily to the societal burden of TB. Individual impacts associated with PIAT may vary by race/ethnicity or socioeconomic status. Methods We analyzed the pulmonary function of 320 prospectively identified patients with pulmonary tuberculosis who had completed at least 20 weeks standard anti-TB regimes by directly observed therapy. We compared frequency and severity of spirometry-defined PIAT in groups stratified by demographics, pulmonary risk factors, and race/ethnicity, and examined clinical correlates to pulmonary function deficits. Results Pulmonary impairment after tuberculosis was identified in 71% of non-Hispanic Whites, 58% of non-Hispanic Blacks, 49% of Asians and 32% of Hispanics (p < 0.001). Predictors for PIAT varied between race/ethnicity. PIAT was evenly distributed across all levels of socioeconomic status suggesting that PIAT and socioeconomic status are not related. PIAT and its severity were significantly associated with abnormal chest x-ray, p < 0.0001. There was no association between race/ethnicity and time to beginning TB treatment, p = 0.978. Conclusions Despite controlling for cigarette smoking, socioeconomic status and time to beginning TB treatment, non-Hispanic White race/ethnicity remained an independent predictor for disproportionately frequent and severe pulmonary impairment after tuberculosis relative to other race/ethnic groups. Since race/ethnicity was self reported and that race is not a biological construct: these findings must be interpreted with caution. However, because race/ethnicity is a proxy for several other unmeasured host, pathogen or environment factors that may contribute to disparate health outcomes, these results are meant to suggest hypotheses for further research.

Abstract Background To test the validity and reliability of scales intended to measure activity limitations faced by children with chronic illnesses living in the community. The scales were based on information provided by caregivers to service program personnel almost exclusively trained as social workers. The items used to measure activity limitations were interRAI items supplemented so that they were more applicable to activity limitations in children with chronic illnesses. In addition, these analyses may shed light on the possibility of gathering functional information that can span the life course as well as spanning different care settings. Methods Analyses included testing the internal consistency, predictive, concurrent, discriminant and construct validity of two activity limitation scales. The scales were developed using assessment data gathered in the United States of America (USA) from over 2,700 assessments of children aged 4 to 20 receiving Medicaid Early and Periodic Screening, Diagnostic and Treatment (EPSDT) services, specifically Personal Care Services to assist children in overcoming activity limitations. The Medicaid program in the USA pays for health care services provided to children in low-income households. Data were collected in a single, large state in the southwestern USA in late 2008 and early 2009. A similar sample of children was assessed in 2010, and the analyses were replicated using this sample. Results The two scales exhibited excellent internal consistency. Evidence on the concurrent, predictive, discriminant, and construct validity of the proposed scales was strong. Quite importantly, scale scores were not correlated with (confounded with) a child's developmental stage or age. The results for these scales and items were consistent across the two independent samples. Conclusions Unpaid caregivers, usually parents, can provide assessors lacking either medical or nursing training with reliable and valid information on the activity limitations of children. One can summarize these data in scales that are both internally consistent and valid. Researchers and clinicians can use supplemented interRAI items to provide guidance for professionals and programs serving children, as well as older persons. This research emphasizes the importance of developing medical information systems that allow one to integrate information not only across care settings but also across an individual's life course.

Abstract Background The health impacts of pulmonary impairment after tuberculosis (TB) treatment have not been included in assessments of TB burden. Therefore, previous global and national TB burden estimates do not reflect the full consequences of surviving TB. We assessed the burden of TB including pulmonary impairment after tuberculosis in Tarrant County, Texas using Disability-adjusted Life Years (DALYs). Methods TB burden was calculated for all culture-confirmed TB patients treated at Tarrant County Public Health between January 2005 and December 2006 using identical methods and life tables as the Global Burden of Disease Study. Years of life-lost were calculated as the difference between life expectancy using standardized life tables and age-at-death from TB. Years lived-with-disability were calculated from age and gender-specific TB disease incidence using published disability weights. Non-fatal health impacts of TB were divided into years lived-with-disability-acute and years lived-with-disability-chronic. Years lived-with-disability-acute was defined as TB burden resulting from illness prior to completion of treatment including the burden from treatment-related side effects. Years lived-with-disability-chronic was defined as TB burden from disability resulting from pulmonary impairment after tuberculosis. Results There were 224 TB cases in the time period, of these 177 were culture confirmed. These 177 subjects lost a total of 1189 DALYs. Of these 1189 DALYs 23% were from years of life-lost, 2% were from years lived-with-disability-acute and 75% were from years lived-with-disability-chronic. Conclusions Our findings demonstrate that the disease burden from TB is greater than previously estimated. Pulmonary impairment after tuberculosis was responsible for the majority of the burden. These data demonstrate that successful TB control efforts may reduce the health burden more than previously recognized.

Abstract Background Flow mapping by cardiovascular magnetic resonance has become the gold standard for non-invasively defining cardiac output (CO), shunt flow and regurgitation. Previous reports have highlighted the presence of inherent errors in flow mapping that are improved with the use of a stationary phantom control. To our knowledge, these studies have only been performed in healthy volunteers. Results We analyzed the variation in flow measurements made with and without stationary phantom correction in 31 patients with congenital heart disease. Variation in stroke volume (SV) measurements was seen in all vessels across all patient groups. The variation was largest when analyzing the right ventricular outflow tract (RVOT), with a range of absolute differences in SV from 0.2 to 70 ml and in CO from 0.02 to 4.8 L/min. In patients with repaired Tetrology of Fallot (ToF), the average ratio of pulmonary to systemic blood flow (Qp:Qs) was 1.18 without and 1.02 with phantom correction. Without performing phantom correction, 23% of the repaired ToF patients were classified as having a residual shunt as compared to 0% when flow mapping was performed with phantom correction. Similarly, in patients with known atrial level shunting (ASD/PAPVR) 20% of patients had no shunt when flow mapping was performed without phantom correction as compared to 0% with phantom correction. In patients with bicuspid aortic valves (BAV), the differences in the regurgitant fraction between measuring flow with and without phantom correction ranged from 0 to 30%, while the regurgitant fraction in the RVOT of ToF patients varied by as much as 31%. Conclusion The impact of inherent errors in CMR flow mapping should not be underestimated. While the variation across a population may not display a significant trend, for any individual patient it can be quite large. Failure to correct for such variation can lead to clinically significant misinterpretation of flow data. The use of the stationary phantom correction technique appears to improve accuracy both in normal patients as well as those with congenital heart disease.

Abstract Background Older veterans may use both the Veterans Health Administration (VHA) and Medicare, but the association of dual use with health outcomes is unclear. We examined the association of indirect measures of dual use with mortality. Methods Our secondary analysis used survey, claims, and National Death Index data from the Survey on Assets and Health Dynamics among the Oldest Old. The analytic sample included 1,521 men who were Medicare beneficiaries. Veterans were classified as dual users when their self-reported number of hospital episodes or physician visits exceeded that in their Medicare claims. Veterans reporting inpatient or outpatient visits but having no Medicare claims were classified as VHA-only users. Proportional hazards regression was used. Results 897 (59%) of the men were veterans, of whom 134 (15%) were dual users. Among dual users, 60 (45%) met the criterion based on inpatient services, 54 (40%) based on outpatient services, and 20 (15%) based on both. 766 men (50%) died. Adjusting for covariates, the independent effect of any dual use was a 38% increased mortality risk (AHR = 1.38; p = .02). Dual use based on outpatient services marginally increased mortality risk by 45% (AHR = 1.45; p = .06), and dual use based on both inpatient and outpatient services increased the risk by 98% (AHR = 1.98; p = .02). Conclusion Indirect measures of dual use were associated with increased mortality risk. New strategies to better coordinate care, such as shared medical records, should be considered.

Abstract Background Millions of veterans are eligible to use the Veterans Health Administration (VHA) and Medicare because of their military service and age. This article examines whether an indirect measure of dual use based on inpatient services is associated with increased mortality risk. Methods Data on 1,566 self-responding men (weighted N = 1,522) from the Survey of Assets and Health Dynamics among the Oldest Old (AHEAD) were linked to Medicare claims and the National Death Index. Dual use was indirectly indicated when the self-reported number of hospital episodes in the 12 months prior to baseline was greater than that observed in the Medicare claims. The independent association of dual use with mortality was estimated using proportional hazards regression. Results 96 (11%) of the veterans were classified as dual users. 766 men (50.3%) had died by December 31, 2002, including 64.9% of the dual users and 49.3% of all others, for an attributable mortality risk of 15.6% (p < .003). Adjusting for demographics, socioeconomics, comorbidity, hospitalization status, and selection bias at baseline, as well as subsequent hospitalization for ambulatory care sensitive conditions, the independent effect of dual use was a 56.1% increased relative risk of mortality (AHR = 1.561; p = .009). Conclusion An indirect measure of veterans' dual use of the VHA and Medicare systems, based on inpatient services, was associated with an increased risk of death. Further examination of dual use, especially in the outpatient setting, is needed, because dual inpatient and dual outpatient use may be different phenomena.

Abstract Background Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. Methods Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. Results Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). Conclusions A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up.

In 2012, 20 key questions related to hazard and exposure assessment and environmental and health risks of pharmaceuticals and personal care products in the natural environment were identified. A decade later, this article examines the current level of knowledge around one of the lowest-ranking questions at that time, number 19: "Can nonanimal testing methods be developed that will provide equivalent or better hazard data compared with current in vivo methods?" The inclusion of alternative methods that replace, reduce, or refine animal testing within the regulatory context of risk and hazard assessment of chemicals generally faces many hurdles, although this varies both by organism (human-centric vs. other), sector, and geographical region or country. Focusing on the past 10 years, only works that might reasonably be considered to contribute to advancements in the field of aquatic environmental risk assessment are highlighted. Particular attention is paid to methods of contemporary interest and importance, representing progress in (1) the development of methods which provide equivalent or better data compared with current in vivo methods such as bioaccumulation, (2) weight of evidence, or (3) -omic-based applications. Evolution and convergence of these risk assessment areas offer the basis for fundamental frameshifts in how data are collated and used for the protection of taxa across the breadth of the aquatic environment. Looking to the future, we are at a tipping point, with a need for a global and inclusive approach to establish consensus. Bringing together these methods (both new and old) for regulatory assessment and decision-making will require a concerted effort and orchestration. Environ Toxicol Chem 2024;43:559-574. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Animals exhibit context-dependent behavioral decisions that are mediated by specific motor circuits. In social species these decisions are often influenced by social status. Although social status-dependent neural plasticity of motor circuits has been investigated in vertebrates, little is known of how cellular plasticity translates into differences in motor activity. Here, we used zebrafish ( Danio rerio ) as a model organism to examine how social dominance influences the activation of swimming and the Mauthner-mediated startle escape behaviors. We show that the status-dependent shift in behavior patterns whereby dominants increase swimming and reduce sensitivity of startle escape while subordinates reduce their swimming and increase startle sensitivity is regulated by the synergistic interactions of dopaminergic, glycinergic, and GABAergic inputs to shift the balance of activation of the underlying motor circuits. This shift is driven by socially induced differences in expression of dopaminergic receptor type 1b (Drd1b) on glycinergic neurons and dopamine (DA) reuptake transporter (DAT). Second, we show that GABAergic input onto glycinergic neurons is strengthened in subordinates compared with dominants. Complementary neurocomputational modeling of the empirical results show that drd1b functions as molecular regulator to facilitate the shift between excitatory and inhibitory pathways. The results illustrate how reconfiguration in network dynamics serves as an adaptive strategy to cope with changes in social environment and are likely conserved and applicable to other social species., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Clements et al.)

Social status-dependent modulation of neural circuits has been investigated extensively in vertebrate and invertebrate systems. However, the effects of social status on neuromodulatory systems that drive motor activity are poorly understood. Zebrafish form a stable social relationship that consists of socially dominant and subordinate animals. The locomotor behavior patterns differ according to their social ranks. The sensitivity of the Mauthner startle escape response in subordinates increases compared to dominants while dominants increase their swimming frequency compared to subordinates. Here, we investigated the role of the endocannabinoid system (ECS) in mediating these differences in motor activities. We show that brain gene expression of key ECS protein pathways are socially regulated. Diacylglycerol lipase (DAGL) expression significantly increased in dominants and significantly decreased in subordinates relative to controls. Moreover, brain gene expression of the cannabinoid 1 receptor (CB 1 R) was significantly increased in subordinates relative to controls. Secondly, increasing ECS activity with JZL184 reversed swimming activity patterns in dominant and subordinate animals. JZL184 did not affect the sensitivity of the startle escape response in dominants while it was significantly reduced in subordinates. Thirdly, blockage of CB 1 R function with AM-251 had no effect on dominants startle escape response sensitivity, but startle sensitivity was significantly reduced in subordinates. Additionally, AM-251 did not affect swimming activities in either social phenotypes. Fourthly, we demonstrate that the effects of ECS modulation of the startle escape circuit is mediated via the dopaminergic system specifically via the dopamine D1 receptor. Finally, our empirical results complemented with neurocomputational modeling suggest that social status influences the ECS to regulate the balance in synaptic strength between excitatory and inhibitory inputs to control the excitability of motor behaviors. Collectively, this study provides new insights of how social factors impact nervous system function to reconfigure the synergistic interactions of neuromodulatory pathways to optimize motor output., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Orr, Ahn, Park, Miller, Kassai and Issa.)

The fate of many chemicals in the environment, particularly contaminants of emerging concern (CEC), have been characterised to a limited extent with a major focus on occurrence in water. This study presents the characterisation, distribution and fate of multiple chemicals including pharmaceuticals, recreational drugs and pesticides in surface water, sediment and fauna representing different food web endpoints in a typical UK estuary (River Colne, Essex, UK). A comparison of contaminant occurrence across different benthic macroinvertebrates was made at three sites and included two amphipods (Gammarus pulex &Crangon crangon), a polychaete worm (Hediste diversicolor) and a gastropod (Peringia ulvae). Overall, multiple contaminants were determined in all compartments and ranged from; -1 in surface water (n = 59 compounds), -1 in sediment (n = 39 compounds) and -1 biota (n = 33 compounds). H. diversicolor and P. ulvae (sediment dwellers) showed greater chemical body burden compared with the two swimming amphipod species sampled (up to 2.5 - 4-fold). The most frequently determined compounds in biota (100%, n = 36 samples) included; cocaine, benzyoylecgonine, carbamazepine, sertraline and diuron. Whilst some of the highest concentrations found were in species H. diverscolor and P. ulvae for psychoactive pharmaceuticals including citalopram (91 ng g -1 ), sertraline (69 ng g -1 ), haloperidol (66 ng g -1 ) and the neonicotinoid, imidacloprid (33 ng g -1 ) Sediment was noted as an important exposure route for these benthic dwelling organisms and will be critical to monitor in future studies. Overall, the analysis of multiple species and compartments demonstrates the importance of including a range of exposure pathways in order to appropriately assess chemical fates and associated risks in the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Multiple classes of environmental contaminants have been found in aquatic environments, globally. Understanding internalised concentrations in the organism could further improve the risk assessment process. The present study is concerned with the determination of several contaminant classes (107 compounds) in Gammarus pulex collected from 15 sites covering 5 river catchments across Suffolk, UK. Quantitative method performance was acceptable for 67 compounds including pharmaceuticals, pesticides, illicit drugs and drugs of abuse. A total of 56 compounds were detectable and ranged from -1 , with cocaine and lidocaine being the most frequently detected compounds present in all biota samples (n = 66). For surface water, 50 compounds were detectable and ranged from -1 . Additionally, some pesticides currently not approved for use were detected, including fenuron that reached a maximum of 16.1 ng g -1 . The internal concentrations of pesticides were used to estimate toxic pressure which showed that for the measured pesticides toxic pressure was low ranging from logTU ≤-7 to ≤-2. This methodology was extended to pharmaceuticals and drugs of abuse in a novel approach that proposed the use of pharmacological data (human therapeutic plasma concentrations) to estimate the likelihood of an effect (or effect pressure) to occur based on the internal exposure of the organism. The quantified effect pressure ranged from logEU ≤-9 to ≤1 with haloperidol showing the largest likelihood for an effect. The approach showed that several pharmaceuticals have the potential to elicit effects but further investigation surrounding thresholds for effects would be required. This new approach presented showed potential to be used to improve risk assessment for pharmaceuticals in the environment., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Modeling approaches such as quantitative structure-activity relationships (QSARs) use molecular descriptors to predict the bioavailable properties of a compound in biota. However, these models have mainly been derived based on empirical data for lipophilic neutral compounds and may not predict the uptake of ionizable compounds. The majority of pharmaceuticals are ionizable, and freshwaters can have a range of pH values that affect speciation. In this study, we assessed the uptake of 10 pharmaceuticals (acetazolamide, beclomethasone, carbamazepine, diclofenac, gemfibrozil, ibuprofen, ketoprofen, norethindrone, propranolol, and warfarin) with differing modes of action and physicochemical properties (p K a , log S, log D, log K ow , molecular weight (MW), and polar surface area (PSA)) by an in vitro primary fish gill cell culture system (FIGCS) for 24 h in artificial freshwater. Principal component analysis (PCA) and partial least-squares (PLS) regression was used to determine the molecular descriptors that influence the uptake rates. Ionizable drugs were taken up by FIGCS; a strong positive correlation was observed between log S and the uptake rate, and a negative correlation was observed between p K a , log D, and MW and the uptake rate. This approach shows that models can be derived on the basis of the physicochemical properties of pharmaceuticals and the use of an in vitro gill system to predict the uptake of other compounds. There is a need for a robust and validated model for gill uptake that could be used in a tiered risk assessment to prioritize compounds for experimental testing.

The application of machine learning has recently gained interest from ecotoxicological fields for its ability to model and predict chemical and/or biological processes, such as the prediction of bioconcentration. However, comparison of different models and the prediction of bioconcentration in invertebrates has not been previously evaluated. A comparison of 24 linear and machine learning models is presented herein for the prediction of bioconcentration in fish and important factors that influenced accumulation identified. R 2 and root mean square error (RMSE) for the test data (n = 110 cases) ranged from 0.23-0.73 and 0.34-1.20, respectively. Model performance was critically assessed with neural networks and tree-based learners showing the best performance. An optimised 4-layer multi-layer perceptron (14 descriptors) was selected for further testing. The model was applied for cross-species prediction of bioconcentration in a freshwater invertebrate, Gammarus pulex. The model for G. pulex showed good performance with R 2 of 0.99 and 0.93 for the verification and test data, respectively. Important molecular descriptors determined to influence bioconcentration were molecular mass (MW), octanol-water distribution coefficient (logD), topological polar surface area (TPSA) and number of nitrogen atoms (nN) among others. Modelling of hazard criteria such as PBT, showed potential to replace the need for animal testing. However, the use of machine learning models in the regulatory context has been minimal to date and is critically discussed herein. The movement away from experimental estimations of accumulation to in silico modelling would enable rapid prioritisation of contaminants that may pose a risk to environmental health and the food chain., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Use of zebrafish as a model organism in biomedical research has led to the generation of many genetically modified mutant lines to investigate various aspects of developmental and cellular processes. However, the broader effects of the underlying mutations on social and motor behavior remain poorly examined. Here, we compared the dynamics of social interactions in the Tüpfel long-fin nacre mutant line, which lacks skin pigmentation, to wild-type zebrafish; and we determined whether status-dependent differences in escape and swimming behavior existed within each strain. We show that despite similarities in aggressive activity, Tüpfel long-fin nacre pairs exhibit unstable social relationships characterized by frequent reversals in social dominance compared to wild-type pairs. The lack of strong dominance relationships in Tüpfel long-fin nacre pairs correlates with weak territoriality and overlapping spatial distribution of dominants and subordinates. Conversely, wild-type dominants displayed strong territoriality that severely limited the movement of subordinates. Additionally, the sensitivity of the startle escape response was significantly higher in wild-type subordinates compared to dominants. However, status-related differences in sensitivity of escape response in Tüpfel long-fin nacre pairs were absent. Finally, we present evidence suggesting that these differences could be a consequence of a disruption of proper visual social signals. We show that in wild-type pairs dominants are more conspicuous, and that in wild-type and Tüpfel long-fin nacre pairings wild-type fish are more likely to dominate Tüpfel long-fin nacres. Our results serve as a cautionary note in research design when morphologically engineered zebrafish for color differences are utilized in the study of social behavior and central nervous system function.

Pharmaceuticals have been considered 'contaminants of emerging concern' for more than 20 years. In that time, many laboratory studies have sought to identify hazard and assess risk in the aquatic environment, whilst field studies have searched for targeted candidates and occurrence trends using advanced analytical techniques. However, a lack of a systematic approach to the detection and quantification of pharmaceuticals has provided a fragmented literature of serendipitous approaches. Evaluation of the extent of the risk for the plethora of human and veterinary pharmaceuticals available requires the reliable measurement of trace levels of contaminants across different environmental compartments (water, sediment, biota - of which biota has been largely neglected). The focus on pharmaceutical concentrations in surface waters and other exposure media have therefore limited both the characterisation of the exposome in aquatic wildlife and the understanding of cause and effect relationships. Here, we compile the current analytical approaches and available occurrence and accumulation data in biota to review the current state of research in the field. Our analysis provides evidence in support of the 'Matthew Effect' and raises critical questions about the use of targeted analyte lists for biomonitoring. We provide six recommendations to stimulate and improve future research avenues., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Methods were developed to assess uptake and elimination kinetics in Gammarus pulex of nine pharmaceuticals (sulfamethazine, carbamazepine, diazepam, temazepam, trimethoprim, warfarin, metoprolol, nifedipine and propranolol) using targeted LC-MS/MS to determine bioconcentration factors (BCFs) using a 96 h toxicokinetic exposure and depuration period. The derived BCFs for these pharmaceuticals did not trigger any regulatory thresholds and ranged from 0 to 73 L kg -1 (sulfamethazine showed no bioconcentration). Metabolism of chemicals can affect accurate BCF determination through parameterisation of the kinetic models. The added selectivity of LC-MS/MS allowed us to develop confirmatory methods to monitor the biotransformation of propranolol, carbamazepine and diazepam in G. pulex. Varying concentrations of the biotransformed products; 4-hydroxypropranolol sulphate, carbamazepine-10,11-epoxide, nordiazepam, oxazepam and temazepam were measured following exposure of the precursor compounds. For diazepam, the biotransformation product nordiazepam was present at higher concentrations than the parent compound at 94 ng g -1 dw. Overall, the results indicate that pharmaceutical accumulation is low in these freshwater amphipods, which can potentially be explained by the rapid biotransformation and excretion., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)