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Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Abstract Nucleation and subsequent growth of new aerosol particles in the atmosphere is a major source of cloud condensation nuclei and persistent large uncertainty in climate models. Newly formed particles need to grow rapidly to avoid scavenging by pre-existing aerosols and become relevant for the climate and air quality. In the continental atmosphere, condensation of oxygenated organic molecules is often the dominant mechanism for rapid growth. However, the huge variety of different organics present in the continental boundary layer makes it challenging to predict nanoparticle growth rates from gas-phase measurements. Moreover, recent studies have shown that growth rates of nanoparticles derived from particle size distribution measurements show surprisingly little dependency on potentially condensable vapors observed in the gas phase. Here, we show that the observed nanoparticle growth rates in the sub-10 nm size range can be predicted in the boreal forest only for springtime conditions, even with state-of-the-art mass spectrometers and particle sizing instruments. We find that, especially under warmer conditions, observed growth is slower than predicted from gas-phase condensation. We show that only a combination of simple particle-phase reaction schemes, phase separation due to non-ideal solution behavior, or particle-phase diffusion limitations can explain the observed lower growth rates. Our analysis provides first insights as to why atmospheric nanoparticle growth rates above 10 nm h−1 are rarely observed. Ultimately, a reduction of experimental uncertainties and improved sub-10 nm particle hygroscopicity and chemical composition measurements are needed to further investigate the occurrence of such a growth rate-limiting process.

Abstract Background Women who experience adverse pregnancy outcomes (APOs; gestational hypertension, preeclampsia (PE), gestational diabetes (GD), preterm birth (PTB), small or large for gestational age, miscarriage, multiple miscarriages, stillbirth, and offspring with major congenital anomalies) have increased risk of developing cardiovascular disease (CVD). We aimed to compare cardiometabolic health trajectories across the life course between women with and without APOs. Methods We studied 187,186 women with a registered pregnancy in the UK Clinical Practice Research Datalink (CPRD) GOLD linked to Hospital Episode Statistics. Fractional polynomial multilevel models were used to compare trajectories of cardiometabolic risk factors (body mass index [BMI], blood pressure [BP], cholesterol, and glucose) between women with and without a history of APOs (individual APOs in any pregnancy and number of APOs). We explored two underlying time axes: (1) time relative to first pregnancy (from 10 years before first pregnancy to 15 years after) and (2) age. Models controlled for age at first pregnancy, residential area deprivation, non-singleton pregnancy, parity, smoking status, ethnicity, and medications use. Results Women with a history of PE, gestational hypertension, or GD had higher BMI, BP, and glucose 10 years before first pregnancy compared to women without these APOs. These differences persisted 15 years post-first pregnancy. Women with a history of GD had a steeper post-partum rise in glucose. Women who experienced multiple (3 +) miscarriage, stillbirth, and/or medically indicated PTB had higher BP and BMI before and after pregnancy, with BP trajectories converging 15 years after first pregnancy. Women who experienced multiple APOs had the most adverse measurements across all cardiometabolic risk factors, with more unfavourable mean levels with each additional APO. There was little difference in cardiometabolic trajectories between women with and without a history of 1 or 2 miscarriages or congenital anomalies. Conclusions Women with APOs had adverse cardiometabolic profiles before first pregnancy, persisting up to 15 years post-pregnancy. Findings highlight the potential for targeted public health interventions to promote good cardiometabolic health in young adults transitioning from contraceptive use to planning pregnancies. APOs may identify young women who could benefit from monitoring CVD risk factors and interventions to improve cardiometabolic health.

Abstract Background Income is associated with many health outcomes, but it is unclear how far this reflects a causal relationship. Mendelian randomisation (MR) uses genetic variation between individuals to investigate causal effects and may overcome some of the confounding issues inherent in many observational study designs. Methods We used two-sample MR using data from unrelated individuals to estimate the effect of log occupational income on indicators of mental health, physical health, and health-related behaviours. We investigated pleiotropy (direct effects of genotype on the outcome) using robust MR estimators, CAUSE, and multivariable MR including education as a co-exposure. We also investigated demographic factors and dynastic effects using within-family analyses, and misspecification of the primary phenotype using bidirectional MR and Steiger filtering. Results We found that a 10% increase in income lowered the odds of depression (OR 0.92 [95% CI 0.86–0.98]), death (0.91 [0.86–0.96]), and ever-smoking (OR 0.91 [0.86–0.96]), and reduced BMI (− 0.06 SD [− 0.11, − 0.003]). We found little evidence of an effect on alcohol consumption (− 0.02 SD [− 0.01, 0.05]) or subjective wellbeing (0.02 SD [− 0.003, 0.04]), or on two negative control outcomes, childhood asthma (OR 0.99 [0.87, 1.13]) and birth weight (− 0.02 SD, [− 0.01, 0.05]). Within-family analysis and multivariable MR including education and income were imprecise, and there was substantial overlap between the genotypes associated with income and education: out of 36 genetic variants significantly associated with income, 29 were also significantly associated with education. Conclusions MR evidence provides some limited support for causal effects of income on some mental health outcomes and health behaviours, but the lack of reliable evidence from approaches accounting for family-level confounding and potential pleiotropic effects of education places considerable caveats on this conclusion. MR may nevertheless be a useful complement to other observational study designs since its assumptions and limitations are radically different. Further research is needed using larger family-based genetic cohorts, and investigating the overlap between income and other socioeconomic measures.

Abstract Background The surgical time-out is a critical safety measure used in the operating room (OR). We examined the mediating relationship of the length of the time-out between team perceived usefulness of the time-out, and the rate at which the circulating nurse left the OR to retrieve instruments. Methods 60 cardiac surgical teams were observed performing their work. The length of the time-out and the rate at which the circulating nurse left the OR was obtained by observation of the surgical team. We administered a survey with a 7-point Likert scale to assess the surgical staff’s perceived usefulness of the time-out at the end of the surgery. An analysis was conducted to test if length of the time-out mediated the relationship between perceived usefulness of the time-out and rate at which the nurse leaves the OR to retrieve an instrument useful for the surgery. Results The relationship of the length of the time-out with the rate at which the nurse leaves the OR was non-significant (β = 0.089, p = .496). However, the relationship between perceived usefulness of the time-out with the length of the time-out was significant (β = 0.346, p

Abstract The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23–4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05–1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01–1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.

Abstract Background Mathematical models and advanced analytics play an important role in policy decision making and mobilizing action. The Imperial College Coronavirus Disease 2019 (COVID-19) Response Team (ICCRT) provided continuous, timely and robust epidemiological analyses to inform the policy responses of governments and public health agencies around the world. This study aims to quantify the policy impact of ICCRT outputs, and understand which evidence was considered policy-relevant during the COVID-19 pandemic. Methods We collated all outputs published by the ICCRT between 01-01-2020 and 24-02-2022 and conducted inductive thematic analysis. A systematic search of the Overton database identified policy document references, as an indicator of policy impact. Results We identified 620 outputs including preprints (16%), reports (29%), journal articles (37%) and news items (18%). More than half (56%) of all reports and preprints were subsequently peer-reviewed and published as a journal article after 202 days on average. Reports and preprints were crucial during the COVID-19 pandemic to the timely distribution of important research findings. One-fifth of ICCRT outputs (21%) were available to or considered by United Kingdom government meetings. Policy documents from 41 countries in 26 different languages referenced 43% of ICCRT outputs, with a mean time between publication and reference in the policy document of 256 days. We analysed a total of 1746 policy document references. Two-thirds (61%) of journal articles, 39% of preprints, 31% of reports and 16% of news items were referenced in one or more policy documents (these 217 outputs had a mean of 8 policy document references per output). The most frequent themes of the evidence produced by the ICCRT reflected the evidence-need for policy decision making, and evolved accordingly from the pre-vaccination phase [severity, healthcare demand and capacity, and non-pharmaceutical interventions (NPIs)] to the vaccination phase of the epidemic (variants and genomics). Conclusion The work produced by the ICCRT affected global and domestic policy during the COVID-19 pandemic. The focus of evidence produced by the ICCRT corresponded with changing policy needs over time. The policy impact from ICCRT news items highlights the effectiveness of this unique communication strategy in addition to traditional research outputs, ensuring research informs policy decisions more effectively.

Abstract Southeast Asia includes several global biodiversity hotspots and bats account for nearly one-third of mammal species currently known in the region. While acoustic methods have become widespread in bat research, basic information is often lacking on the echolocation calls produced by Asian bat species. Since such information can aid a wide variety of research and conservation initiatives, descriptions of the calls emitted by Asian bats are fundamental. The aim of our study was to provide a standardized analysis and description of the Vietnamese bat echolocation calls. We analyzed call recordings of 87 species arranged in eight families. This constitutes 74% of the echolocating bats presently known in Vietnam and includes the first call descriptions for five taxa. Our use of an open-source software and the deposition of recordings in the ChiroVox repository will facilitate comparative studies in Asia and the information we provide represents one of the most comprehensive bioacoustic databases for Asian bats to date.

Children born to parents with fewer years of education are more likely to have depression, anxiety, and attention-deficit hyperactivity disorder (ADHD), but it is unclear to what extent these associations are causal. We estimated the effect of parents' educational attainment on children's depressive, anxiety, and ADHD traits at age 8 years, in a sample of 40,879 Norwegian children born in 1998-2009 and their parents. We used within-family Mendelian randomization, which employs genetic variants as instrumental variables, and controlled for direct genetic effects by adjusting for children's polygenic indexes. We found little evidence that mothers' or fathers' educational attainment independently affected children's depressive, anxiety, or ADHD traits. However, children's own polygenic scores for educational attainment were independently and negatively associated with these traits. Results suggest that differences in these traits according to parents' education may reflect direct genetic effects more than genetic nurture. Consequences of social disadvantage for children's mental health may however be more visible in samples with more socioeconomic variation, or contexts with larger socioeconomic disparities than present-day Norway. Further research is required in populations with more educational and economic inequality and in other age groups.

Background There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone. Methods and findings We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink. We included adults diagnosed with severe mental illness (i.e., bipolar disorder, schizophrenia, and other non-organic psychoses) who were prescribed a new antipsychotic between 2005 and 2017, with a 2-year follow-up to 2019. The primary outcome was total cholesterol at 1 year (cardiometabolic safety). The main secondary outcome was psychiatric hospitalisation (effectiveness). Other outcomes included body weight, blood pressure, all-cause discontinuation, and mortality. Analyses adjusted for baseline confounders, including sociodemographics, diagnoses, concomitant medications, and cardiometabolic parameters. We included 26,537 patients (aripiprazole, n = 3,573, olanzapine, n = 8,554, quetiapine, n = 8,289, risperidone, n = 6,121). Median (IQR) age was 53 (42-67) years, 55.4% were female, 82.3% White, and 18.0% were diagnosed with schizophrenia. Patients prescribed aripiprazole had similar total cholesterol levels after 1 year to those prescribed olanzapine (adjusted mean difference [aMD], -0.03, 95% CI, -0.09 to 0.02, p = 0.261), quetiapine (aMD, -0.03, 95% CI, -0.09 to 0.03, p = 0.324), and risperidone (aMD, -0.01, 95% CI, -0.08 to 0.05, p = 0.707). However, there was evidence that patients prescribed aripiprazole had better outcomes on other cardiometabolic parameters, such as body weight and blood pressure, especially compared to olanzapine. After additional adjustment for prior hospitalisation, patients prescribed aripiprazole had similar rates of psychiatric hospitalisation as those prescribed olanzapine (adjusted hazard ratio [aHR], 0.91, 95% CI, 0.82 to 1.01, p = 0.078), quetiapine (aHR, 0.94, 95% CI, 0.85 to 1.04, p = 0.230), or risperidone (aHR, 1.01, 95% CI, 0.91 to 1.12, p = 0.854). Conclusions Data from our large, powered, diverse, real-world target trial emulation sample, followed over 2 years, suggest that adults diagnosed with severe mental illness prescribed aripiprazole have similar total cholesterol 1 year after first prescription compared to those prescribed olanzapine, quetiapine, and risperidone. However, patients prescribed aripiprazole had better outcomes on some other cardiometabolic parameters, and there was little evidence of differences in effectiveness. Our findings inform a common clinical dilemma and contribute to the evidence base for real-world clinical decision-making on antipsychotic choice for patients diagnosed with severe mental illness., Author(s): Alvin Richards-Belle 1,*, Naomi Launders 1, Sarah Hardoon 1, Al Richards 2, Kenneth K.C. Man 3,4,5,6, Neil M. Davies 1,7,8, Elvira Bramon 1,9, Joseph F. Hayes 1,9, David P.J. [...]

Abstract During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

Blood transfusion, a vital medical intervention, is susceptible to errors in the laboratory phase, which can lead to severe consequences. This systematic review explores the literature on laboratory errors in blood transfusion, highlighting the impact of these errors on patient safety and outcomes. It also presents strategies for error prevention and management. The review underscores the potential for improvement in blood transfusion services through ongoing quality improvement efforts, a responsibility for all of us. After a comprehensive search and analysis of relevant literature published from 2014 to 2024 under PARSMA2020 guidelines, nine articles met the inclusion criteria, revealing a range of errors across different stages of the transfusion process. Preanalytical errors were found to be the most common. Procedural deviations, insufficient collaboration, and work fatigue among medical staff were identified as the causes of these errors. The review suggests that implementing educational and contentious training programs for medical staff, along with highly accountable policies, could significantly reduce these errors, thereby reducing total mortality and morbidity rates.

Atmospheric simulation chambers continue to be indispensable tools for research in the atmospheric sciences. Insights from chamber studies are integrated into atmospheric chemical transport models, which are used for science-informed policy decisions. However, a centralized data management and access infrastructure for their scientific products had not been available in the United States and many parts of the world. ICARUS (Integrated Chamber Atmospheric data Repository for Unified Science) is an open access, searchable, web-based infrastructure for storing, sharing, discovering, and utilizing atmospheric chamber data [https://icarus.ucdavis.edu]. ICARUS has two parts: a data intake portal and a search and discovery portal. Data in ICARUS are curated, uniform, interactive, indexed on popular search engines, mirrored by other repositories, version-tracked, vocabulary-controlled, and citable. ICARUS hosts both legacy data and new data in compliance with open access data mandates. Targeted data discovery is available based on key experimental parameters, including organic reactants and mixtures that are managed using the PubChem chemical database, oxidant information, nitrogen oxide (NOx) content, alkylperoxy radical (RO2) fate, seed particle information, environmental conditions, and reaction categories. A discipline-specific repository such as ICARUS with high amounts of metadata works to support the evaluation and revision of atmospheric model mechanisms, intercomparison of data and models, and the development of new model frameworks that can have more predictive power in the current and future atmosphere. The open accessibility and interactive nature of ICARUS data may also be useful for teaching, data mining, and training machine learning models.

Heuristics can inform human decision making in complex environments through a reduction of computational requirements (accuracy-resource trade-off) and a robustness to overparameterisation (less-is-more). However, tasks capturing the efficiency of heuristics typically ignore action proficiency in determining rewards. The requisite movement parameterisation in sensorimotor control questions whether heuristics preserve efficiency when actions are nontrivial. We developed a novel action selection-execution task requiring joint optimisation of action selection and spatio-temporal skillful execution. State-appropriate choices could be determined by a simple spatial heuristic, or by more complex planning. Computational models of action selection parsimoniously distinguished human participants who adopted the heuristic from those using a more complex planning strategy. Broader comparative analyses then revealed that participants using the heuristic showed combined decisional (selection) and skill (execution) advantages, consistent with a less-is-more framework. In addition, the skill advantage of the heuristic group was predominantly in the core spatial features that also shaped their decision policy, evidence that the dimensions of information guiding action selection might be yoked to salient features in skill learning.

IntroductionMelittin is a potent antimicrobial peptide from bee venom that is effective against both Gram-positive and Gram-negative bacteria. However, it is extremely toxic to mammalian cells and, as yet, has no clinical use. Modifications to its amino acid sequence, cyclization, truncation, and dimerization have been attempted in order to reduce its toxicity whilst maintaining its antimicrobial activity.MethodsIn this study, we targeted the three lysine residues present in melittin and substituted them with lysine homologs containing shorter side chains (ornithine, Orn, diaminobutyric acid, Dab, and diaminopropanoic acid, Dap) and made both parallel and antiparallel melittin dimers to observe how lysine substitution and dimerization affects its activity and toxicity. The antibacterial activity of melittin and its analogs was tested against S. aureus (Gram-positive bacteria) and E. coli (Gram-negative bacteria), and cytotoxicity was tested against the mammalian cell lines HEK293 and H4IIE.ResultsOverall, dimerization and lysine substitution exhibited improved antimicrobial activity toward E. coli and limited improvement toward S. aureus. However, mammalian cell toxicity was only marginally reduced compared to native melittin. Interestingly, the parallel dimer was found to be marginally more active than the antiparallel dimer, indicating orientation maybe important for activity, although both dimers were less effective than the native and Lys-analog peptides toward S. aureus. Of the Lys substitutions, Dab and Dap improved melittin’s activity toward E. coli.DiscussionDimerization and Lys substitution of melittin improved the antimicrobial activity toward Gram-negative bacteria but did not significantly improve its activity toward Gram-positive bacteria. Some analogs also displayed reduced toxicity toward HEK293 and H4IIE cells but overall remained toxic at bactericidal concentrations. Our data indicates that although highly antibacterial, melittin’s toxicity is the major drawback in its potential use.

Introduction : Independent Living residences for older adults can be divided into two categories and require better definitions for research purposes; the purpose of this manuscript is to provide those definitions and explore variation in provided services and resident characteristics: (a) Subsidized age-based housing (55+) (Department of Housing and Urban Development (HUD) housing units for low-income adults), and (b) non-subsidized age-based housing. Methods: Residents in the two settings were compared: 37 subsidized locations ( p = 289 residents) and 19 non-subsidized ( p = 208). Aging support services in each housing type were quantified. Results: Subsidized residents are more likely to be female (84.6% vs. 70.2%, p = .0002) and have fair-poor health (36.5% vs. 12.5%, p

This paper draws on both a theoretical understanding and a semi-autoethnographic approach of the lived experience of working class adult learners in higher education during the COVID-19 global pandemic. In particular, the paper warns of the doxic notion of current working class struggles being singularly attributed to COVID-19. Rather it is vital to assert that the societal structures that frame and reproduce inequality -- written by the dominant classes and cultures -- are the root of the problem. The daily struggles of working class adult learners have been amplified by the pandemic, but through Freire's love as a political force, there is space for radical hope.

BackgroundFalls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk.MethodsWe assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL.ResultsFor recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months.ConclusionsAcross a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects.Clinicaltrialsgov identifier: NCT02475850.

Reactive oxygen species (ROS) and environmentally persistent free radicals (EPFR) play an important role in chemical transformation of atmospheric aerosols and adverse aerosol health effects. This study investigated the effects of nitrogen oxides (NOx) during photooxidation of α-pinene and naphthalene on the EPFR content and ROS formation from secondary organic aerosols (SOA). Electron paramagnetic resonance (EPR) spectroscopy was applied to quantify EPFR content and ROS formation. While no EPFR were detected in α-pinene SOA, we found that naphthalene SOA contained about 0.7 pmol μg-1 of EPFR, and NOx has little influence on EPFR concentrations and oxidative potential. α-Pinene and naphthalene SOA generated under low NOx conditions form OH radicals and superoxide in the aqueous phase, which was lowered substantially by 50-80% for SOA generated under high NOx conditions. High-resolution mass spectrometry analysis showed the substantial formation of nitroaromatics and organic nitrates in a high NOx environment. The modeling results using the GECKO-A model that simulates explicit gas-phase chemistry and the radical 2D-VBS model that treats autoxidation predicted reduced formation of hydroperoxides and enhanced formation of organic nitrates under high NOx due to the reactions of peroxy radicals with NOx instead of their reactions with HO2. Consistently, the presence of NOx resulted in the decrease of peroxide contents and oxidative potential of α-pinene SOA.