Abstract Active travel (cycling, walking) is beneficial for the health due to increased physical activity (PA). However, active travel may increase the intake of air pollution, leading to negative ...health consequences. We examined the risk–benefit balance between active travel related PA and exposure to air pollution across a range of air pollution and PA scenarios. The health effects of active travel and air pollution were estimated through changes in all-cause mortality for different levels of active travel and air pollution. Air pollution exposure was estimated through changes in background concentrations of fine particulate matter (PM2.5 ), ranging from 5 to 200 μg/m3. For active travel exposure, we estimated cycling and walking from 0 up to 16 h per day, respectively. These refer to long-term average levels of active travel and PM2.5 exposure. For the global average urban background PM2.5 concentration (22 μg/m3) benefits of PA by far outweigh risks from air pollution even under the most extreme levels of active travel. In areas with PM2.5 concentrations of 100 μg/m3, harms would exceed benefits after 1 h 30 min of cycling per day or more than 10 h of walking per day. If the counterfactual was driving, rather than staying at home, the benefits of PA would exceed harms from air pollution up to 3 h 30 min of cycling per day. The results were sensitive to dose–response function (DRF) assumptions for PM2.5 and PA. PA benefits of active travel outweighed the harm caused by air pollution in all but the most extreme air pollution concentrations.
Context The mental health benefits of physical activity are well established. However, less is known about whether the relationship between physical activity and mental health is consistent across ...different life domains. It is important to understand how context may influence the relationship between physical activity and mental health so that interventions and policy guidelines can be tailored to maximize positive effects. Evidence acquisition In 2015, systematic searches of four databases identified 13,435 records, of which 98 studies met the inclusion criteria. Evidence synthesis Included studies were published between 1988 and 2015 and had a combined sample size of 648,726. Of the 98 included studies, 93 examined leisure-time physical activity, 14 examined work-related physical activity, 15 examined transport physical activity, 16 examined household physical activity, three examined school sport, and three examined physical education. Multi-level meta-analyses showed that leisure-time physical activity ( r =0.13) and transport physical activity ( r =0.13) both had a positive association with mental health. Leisure-time physical activity ( r = –0.11) and school sport ( r = –0.09) both had an inverse association with mental ill-health. However, physical activity was not consistently associated with lower mental ill-health across domains, as work-related physical activity was positively associated with mental ill-health ( r =0.09). Household physical activity and participation in physical education had no relationship with mental health or mental ill-health. Conclusions The domain in which physical activity occurs influences the relationship between physical activity and mental health and should, therefore, be considered when developing interventions, treatment programs, and policy guidelines.
Per- and polyfluoroalkyl substances in the environment Evich, Marina G; Davis, Mary J B; McCord, James P ...
Science (American Association for the Advancement of Science),
02/2022, Volume:
375, Issue:
6580
Journal Article
Peer reviewed
Open access
Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS ...are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water.
X-ray photoelectron (XPS) experiments at normal and grazing emission are performed, demonstrating the labile nature of the anatase TiO2(101) surface after argon cluster ion sputtering and the ...propensity of oxygen vacancies to migrate subsurface at room temperature. Near-ambient XPS (NAP-XPS) shows that molecular water adsorbs on the anatase TiO2(101) surface at pressures of 0.6 mbar and above, at room temperature, in a mixed molecular and dissociated state. Water adsorbs in a similar fashion on both sputtered and stoichiometric surfaces and reaches a saturation point between 0.6 and 1.8 mbar at room temperature. This means there is little difference in reactivity with regards to water adsorption on both sputtered and stoichiometric surfaces, giving credence to the theory that anatase has superior photocatalytic activity over rutile due to the tendency of oxygen vacancies to lie subsurface, therefore being able to contribute to photocatalysis without being quenched by adsorbates.
Global concern over widely documented declines in pollinators
has led to the identification of anthropogenic stressors that, individually, are detrimental to bee populations
. Synergistic ...interactions between these stressors could substantially amplify the environmental effect of these stressors and could therefore have important implications for policy decisions that aim to improve the health of pollinators
. Here, to quantitatively assess the scale of this threat, we conducted a meta-analysis of 356 interaction effect sizes from 90 studies in which bees were exposed to combinations of agrochemicals, nutritional stressors and/or parasites. We found an overall synergistic effect between multiple stressors on bee mortality. Subgroup analysis of bee mortality revealed strong evidence for synergy when bees were exposed to multiple agrochemicals at field-realistic levels, but interactions were not greater than additive expectations when bees were exposed to parasites and/or nutritional stressors. All interactive effects on proxies of fitness, behaviour, parasite load and immune responses were either additive or antagonistic; therefore, the potential mechanisms that drive the observed synergistic interactions for bee mortality remain unclear. Environmental risk assessment schemes that assume additive effects of the risk of agrochemical exposure may underestimate the interactive effect of anthropogenic stressors on bee mortality and will fail to protect the pollinators that provide a key ecosystem service that underpins sustainable agriculture.
Summary Background Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium ...retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure. Methods In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18–79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or ≥135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25–50 mg), bisoprolol (5–10 mg), doxazosin modified release (4–8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number, NCT02369081. Findings Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients completed all treatment cycles. The average reduction in home systolic blood pressure by spironolactone was superior to placebo (–8·70 mm Hg 95% CI −9·72 to −7·69; p<0·0001), superior to the mean of the other two active treatments (doxazosin and bisoprolol; −4·26 –5·13 to −3·38; p<0·0001), and superior when compared with the individual treatments; versus doxazosin (–4·03 –5·04 to −3·02; p<0·0001) and versus bisoprolol (–4·48 –5·50 to −3·46; p<0·0001). Spironolactone was the most effective blood pressure-lowering treatment, throughout the distribution of baseline plasma renin; but its margin of superiority and likelihood of being the best drug for the individual patient were many-fold greater in the lower than higher ends of the distribution. All treatments were well tolerated. In six of the 285 patients who received spironolactone, serum potassium exceeded 6·0 mmol/L on one occasion. Interpretation Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition. Funding The British Heart Foundation and National Institute for Health Research.
When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may ...also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, Americamysis bahia with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater) and stressful conditions (diluted seawater). The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis.
Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation between AFLP diversity and population fitness overall; however, AFLP markers performed poorly at detecting modest but consequential losses of genetic diversity. High diversity lines in the stressful environment showed some evidence of relative improvement as the experiment progressed while the low diversity lines did not.
The combined effects of reduced average fitness and increased variability contributed to increased extinction rates for very low diversity populations. More modest losses of genetic diversity resulted in measurable decreases in population fitness; AFLP markers did not always detect these losses. However when AFLP markers indicated lost genetic diversity, these losses were associated with reduced population fitness.
Convolutional neural networks (CNNs) are deep learning network architectures that have pushed forward the state-of-the-art in a range of computer vision applications and are increasingly popular in ...medical image analysis. However, training of CNNs is time-consuming and challenging. In medical image analysis tasks, the majority of training examples are easy to classify and therefore contribute little to the CNN learning process. In this paper, we propose a method to improve and speed-up the CNN training for medical image analysis tasks by dynamically selecting misclassified negative samples during training. Training samples are heuristically sampled based on classification by the current status of the CNN. Weights are assigned to the training samples and informative samples are more likely to be included in the next CNN training iteration. We evaluated and compared our proposed method by training a CNN with (SeS) and without (NSeS) the selective sampling method. We focus on the detection of hemorrhages in color fundus images. A decreased training time from 170 epochs to 60 epochs with an increased performance-on par with two human experts-was achieved with areas under the receiver operating characteristics curve of 0.894 and 0.972 on two data sets. The SeS CNN statistically outperformed the NSeS CNN on an independent test set.
For the past 30 years, improvements in the survival of patients with osteosarcoma have been mostly incremental. Despite evidence of genomic instability and a high frequency of chromothripsis and ...kataegis, osteosarcomas carry few recurrent targetable mutations, and trials of targeted agents have been generally disappointing. Bone has a highly specialized immune environment and many immune signalling pathways are important in bone homeostasis. The success of the innate immune stimulant mifamurtide in the adjuvant treatment of non-metastatic osteosarcoma suggests that newer immune-based treatments, such as immune checkpoint inhibitors, may substantially improve disease outcome.
Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line ...drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation or efflux. Using this method, we identified resistance-linked genes for eight compounds with anti-tubercular activity. Four of the genes have previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS and Pks13 represent novel targets in protein translation and cell-wall biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13, AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and the availability of whole-cell active inhibitors greatly increases their potential for drug discovery.
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