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Teachers are pivotal in creating safe and efficacious learning environments for ethnic minority students. Research suggests that teachers' multicultural attitudes, self-efficacy, and wellbeing at work may all play important roles in this endeavor. Using survey data on 433 teachers in Belgium, Denmark, Finland, Norway, Sweden, and the United Kingdom, the present study used structural equation models to analyze the paths between teachers' multicultural attitudes and work-related wellbeing (work dedication and exhaustion), and whether self-efficacy mediates these paths. We further investigated how these associations differ between teachers of reception classes for migrant and refugee students versus teachers of multi-ethnic mainstream classes. The results show that positive multicultural attitudes were directly associated with high level of work dedication, but not with work exhaustion. Self-efficacy mediated the association between multicultural attitudes and work-related wellbeing, indicated by both higher work dedication and lower work exhaustion. Concerning the role of teacher's class type, self-efficacy mediated the association between positive multicultural attitudes and work dedication for both types of teachers, whereas the mediation to low work exhaustion was only evident in mainstream class teachers. To conclude, teachers' multicultural attitudes and work-related wellbeing are mediated by self-efficacy and this important link should be acknowledged when designing professional development programs in order to create supportive and competent learning environments for all students.

Abstract Marine sediments are archives of environmental change with pollutants potentially acting as chronographic markers of the Anthropocene. Particularly, the vertical transport and burial, as well as slow degradation rate of microplastics, indicate an eventual incorporation into the geological record. A high-resolution reconstruction of microplastics records requires high sedimentation rates, and in Disko Bay (Greenland), this quality coincides with a need for plastic pollution data. Here, a Greenlandic sediment core dated back to 1930 ± 2 was reconstructed for microplastics accumulation via micro-Fourier transform infrared spectroscopy. We show 85 years of fluctuating microplastics accumulation (987 − 16,645 particles Kg−1) down to 20 µm and diversified into eight polymers. Polyethylene (47%) and polypropylene (32%) were more abundantly present through time. Microplastics accumulation increases significantly after 1950 along with major socio-economic development in the area, suggesting an influence from regional stressors. Regional microplastics reconstructions must therefore be considered in the pursuit of an Anthropocene global plastic horizon.

Phytochemical investigation of the leaf extract of Uvaria grandiflora Roxb. ex Hornem led to the isolation and identification of two new highly oxygenated cyclohexenes, uvariagrandols A (1) and B (2), together with seven known compounds (3–9). Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. The (1S,2S,3R,6S) absolute configuration of uvariagrandols A and B was established by the comparison of the experimental and calculated electronic circular dichroism (ECD). (+)-Grandifloracin (9) displayed cytotoxicity against SW480 and K562 cell lines with IC50 values of 154.9 and 60.9 μM, respectively. 6-Methoxyzeylenol (5) had α-glucosidase inhibitory activity with the IC50 value of 34.1 μM.

Background: Refugee and non-refugee migrant youths may carry a double burden of past adversities and post-migration stress while trying to continue schooling and adapt to their new social and cultural environment. Executive functioning skills are central to learning and navigating in the new context. Knowledge of how young migrants’ executive functioning is associated with stressful factors and positive or potentially protective factors, could contribute to understanding and possibly finding ways to support these young learners.Objective: To investigate how potentially stressful and positive factors are associated with executive function skills.Method: In a secondary, explorative analysis of questionnaire responses from 1312 migrant students in secondary schools in five European countries, the associations of planning- and initiative executive function skills (PIS-EF) with stressful factors (e.g. emotional and behavioural problems, daily stress, discrimination) and positive factors (e.g. resilience, school belonging, social support) were analysed by linear regression. Furthermore, differences between male/female and refugee/non-refugee migrants were examined.Results: Positive factors accounted for almost one-fifth of the variance in the students’ self-reported PIS-EF and stress factors only one-tenth. Resilience showed the strongest association with students’ PIS-EF, followed by Prosocial behaviour and School belonging. Hyperactivity, and symptoms of anxiety and depression were negatively associated with PIS-EF. Posttraumatic stress symptoms were minimally associated with the investigated aspects of executive functions. Adjusted for other variables, no variables showed significant differences in the association with EF between males and females, and refugee and non-refugee migrant students.Conclusions: Positive factors were more strongly associated with executive functioning than stressful factors and could represent pathways to strengthen executive functioning. To support migrant youths’ functioning, the school, healthcare, and social systems should take a resource-oriented perspective and lay the ground for migrant youth's feeling of belongingness and active use of their personal resources.

ABSTRACTBackground: High levels of post-traumatic stress are well documented among refugees. Yet, refugee adolescents display high heterogeneity in their type of trauma and symptom levels.Objective: Following the recurrent plea for validated trauma screening tools, this study investigated the psychometric properties of the Children’s Revised Impact of Event Scale (CRIES-8) among refugee adolescents from Afghanistan (n = 148), Syria (n = 234), and Somalia (n = 175) living in Europe.Method: The model fit for the confirmatory factor structures was tested, as well as measurement invariance between the three groups. The robustness of results was evaluated by testing measurement invariance between recently arrived and settled adolescents, and between different response labelling options. Reliability (α, ω, and ordinal α), criterion validity, and prevalence estimates were calculated.Results: The intrusion subscale showed a better stable model fit than the avoidance subscale, but the two-factor structure was mainly supported. Configural measurement invariance was achieved between Afghan and Somali adolescents, and strong measurement invariance between Syrian and Somali adolescents. The results were robust considering the time living in the host country and response labelling styles. Reliability was low among Afghan and Syrian adolescents (.717−.856), whereas it was higher among Somali adolescents (.831−.887). The total score had medium-sized correlations with emotional problems (.303−.418) and low correlations with hyperactivity (.077−.155). There were statistically significant differences in symptom prevalence: Afghan adolescents had higher prevalence (55.5%) than Syrian (42.8%) and Somali (37%) adolescents, and unaccompanied refugee minors had higher symptom prevalence (63.5%) than accompanied adolescents (40.7%).Conclusions: This study mostly supports the use of the CRIES-8 among adolescents from Afghanistan, Syria, and Somalia, and even comparative analyses of group means. Variation in reliability estimates, however, makes diagnostic predictions difficult, as the risk of misclassification is high.

Summary: Background: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort. Methods: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseline until end of follow-up, road, railway, and aircraft noise was estimated at a residential level. Incident AF was ascertained via linkage to nationwide patient registries. Cox proportional hazards models were utilized to estimate associations between running 5-year time-weighted mean transportation noise (Lden) and AF after adjusting for sociodemographics, lifestyle, and air pollution. Findings: We identified 18,939 incident AF cases over a median follow-up of 19.6 years. Road traffic noise was associated with AF, with a hazard ratio (HR) and 95% confidence interval (CI) of 1.02 (1.00–1.04) per 10-dB of 5-year mean time-weighted exposure, which changed to 1.03 (1.01–1.06) when implementing a 53-dB cut-off. In effect modification analyses, the association for road traffic noise and AF appeared strongest in women and overweight and obese participants. Compared to exposures ≤40 dB, aircraft noise of 40.1–50 and > 50 dB were associated with HRs of 1.04 (0.93–1.16) and 1.12 (0.98–1.27), respectively. Railway noise was not associated with AF. We found a HR of 1.19 (1.02–1.40) among people exposed to noise from road (≥45 dB), railway (>40 dB), and aircraft (>40 dB) combined. Interpretation: Road traffic noise, and possibly aircraft noise, may be associated with elevated risk of AF. Funding: NordForsk.

Chronic stress and elevated cortisol are associated with adverse metabolic profiles and lifestyle patterns, systemic low-grade inflammation, and increased chronic disease risk; however, it is less clear how the degree of cortisol fluctuations impacts these parameters. Adult men and women (18-70y) were recruited to participate in a 5-day observational study, in which they underwent a baseline health and body composition assessment, completed 5-day diet, exercise, and stress records, and provided saliva samples in the morning, afternoon, and evening to measure fluctuations in cortisol, interleukin-1β (IL-1β), and IL-6. Degree of cortisol variability over the 5-day period (highest cortisol measure - lowest cortisol measure) was used to classify subjects into high (n = 9) and low (n = 9) cortisol fluctuation groups. Participants with greater fluctuations in salivary cortisol had higher salivary cortisol concentrations on average, which was attributed to higher maximal and morning cortisol. A greater proportion of individuals with higher cortisol flux worked in first responder/emergency professions, and exhibited minimal dietary pattern differences compared to those with low cortisol flux. While body fat percentage and mass positively correlated with minimum salivary cortisol measures, body composition and blood pressure did not differ between low vs. high salivary cortisol flux groups. Interestingly, we observed diurnal patterns of salivary IL-1β concentrations, with higher IL-1β in the morning, and greater afternoon IL-1β in the high cortisol flux group compared to the low cortisol flux group. Independent of cortisol flux, waking satiety and intake patterns of dietary nutrients and food groups/type differentially correlated with salivary cytokine concentrations in a time of day-dependent manner. Our findings suggest that greater fluctuations in cortisol are associated with distinct diurnal salivary cortisol and IL-1β concentrations but minimal lifestyle and dietary factors, whereas dietary patterns are strongly and differentially associated with salivary cytokine profiles.

Abstract Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

Abstract Sediment discharged from the Greenland Ice Sheet delivers nutrients to marine ecosystems around Greenland and shapes seafloor habitats. Current estimates of the total sediment flux are constrained by observations from land-terminating glaciers only. Addressing this gap, our study presents a budget derived from observations at 30 marine-margin locations. Analyzing sediment cores from nine glaciated fjords, we assess spatial deposition since 1950. A significant correlation is established between mass accumulation rates, normalized by surface runoff, and distance down-fjord. This enables calculating annual sediment flux at any fjord point based on nearby marine-terminating outlet glacier melt data. Findings reveal a total annual sediment flux of 1.324 + /− 0.79 Gt yr-1 over the period 2010-2020 from all marine-terminating glaciers to the fjords. These estimates are valuable for studies aiming to understand the basal ice sheet conditions and for studies predicting ecosystem changes in Greenland’s fjords and offshore areas as the ice sheet melts and sediment discharge increase.

Abstract Understanding the genetic basis of convergence at broad phylogenetic scales remains a key challenge in biology. Kingfishers (Aves: Alcedinidae) are a cosmopolitan avian radiation with diverse colors, diets, and feeding behaviors—including the archetypal plunge-dive into water. Given the sensory and locomotor challenges associated with air-water transitions, kingfishers offer a powerful opportunity to explore the effects of convergent behaviors on the evolution of genomes and phenotypes, as well as direct comparisons between continental and island lineages. Here, we use whole-genome sequencing of 30 diverse kingfisher species to identify the genomic signatures associated with convergent feeding behaviors. We show that species with smaller ranges (i.e., on islands) have experienced stronger demographic fluctuations than those on continents, and that these differences have influenced the dynamics of molecular evolution. Comparative genomic analyses reveal positive selection and genomic convergence in brain and dietary genes in plunge-divers. These findings enhance our understanding of the connections between genotype and phenotype in a diverse avian radiation.

Nutritional status, sex, and physical activity have been implicated in severe COVID-19 illness; however, the role of lifestyle factors and nutritional status in determining an individual's response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines is less well characterized. We evaluated whether self-reported side effects following SARS-CoV2 vaccination differed by body mass index (BMI) and lifestyle factors. We further evaluated whether associations between lifestyle, nutritional status, and self-reported side effects differed by sex or use of hormone-based medications. A survey was administered between May–September 2021 to collect respondents' self-reported demographics, dietary patterns, physical activity, medication and supplement use, history of COVID-19 illness, and SARS-CoV2 vaccine side effects. A total of 82 participants (61.2 % female, 38.8 % male) completed the survey and were included in the final analysis. Females trended toward reporting a greater level of subjective stress (71 %) and engaged in less physical activity (43.2 %) compared to males. While severity of COVID-19 illness and vaccine side effects did not differ by sex and there were no differences in dietary patterns between individuals reporting mild vs. more severe side effects, individuals with a higher BMI trended toward reporting a greater severity of vaccine side effects. Survey participants who engaged in physical activity for more than 30 min per day trended toward reporting a lower severity of side effects compared to those exercising for 30 min a day or less after the first dose (86.7 % vs. 50.0 %), whereas the opposite trend was observed following the second mRNA vaccine dose. In addition, survey participants reporting higher stress levels experienced a greater severity of side effects of the first SARS-CoV2 mRNA vaccine dose compared to those reporting lower stress levels (42.9 % vs. 2.0 %). Further, a greater percentage (75 %) of respondents taking combined oral contraceptives reported experiencing side effects following the first SARS-CoV2 mRNA vaccine dose, whereas participants not using hormone-based contraceptives were more likely to report not experiencing side effects (61.3 %). Together, our findings suggest that self-reported side effects from SARS-CoV2 mRNA vaccines differ by lifestyle characteristics and use of combined oral contraceptives. Further investigation is warranted to determine whether targeting these lifestyle factors is an effective strategy to mitigate vaccine side effects, and whether public health education pertaining to lifestyle and anticipated side effects may reduce the barriers to vaccine acceptance.

Liver X receptor (LXR) agonists, including synthetic ligands or naturally-occurring oxysterols, exert promising lipid-modulating, anti-inflammatory, and anti-tumor effects. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) whole cell mass spectrometry (MS) shows promise in chronic disease and food science research, clinical diagnostics of cancer cells and bacterial pathogens, and drug/nutraceutical discovery due to its relatively low-cost, rapid, reliable, and high-throughput ability to identify unique cell phenotypes and differentiation states of immune cells that play essential roles in chronic metabolic and inflammatory disease pathophysiology. However, optimization of whole cell MALDI-TOF MS-based methods to assess cellular changes in response to pharmaceutical and/or nutraceutical treatment warrants further study. Thus, we investigated whether whole cell MALDI-TOF MS could detect cellular phenotype changes of human stem-like erythroleukemia K562 cells – a model for chronic myelogenous leukemia (CML) – induced by the LXR agonist TO-901317, a synthetic ligand that mimics effects of naturally-occurring oxysterols, which are oxidized cholesterol derivatives formed under conditions of high cellular cholesterol concentrations and in food products. TO-901317 dose- and time-dependently altered mRNA expression of cholesterol flux genes, including ATP-binding cassette transporter A1 (ABCA1), LDL-receptor (LDLR), HMG-CoA reductase (HMGCR), and reduced cellular cholesterol content by 22.9% at 24 h. TO-901317 additionally dose- and time-dependently impacted K562 cell viability, number, size, and reduced mRNA expression of the anti-apoptotic gene BCL2L1 by 43.3%. These effects corresponded to induced gene expression of erythroid markers and hemoglobin content, suggesting that LXR activation may promote erythroid lineage differentiation. Whole cell MALDI-TOF MS mass fingerprinting revealed distinct proteomic phenotypes between TO-901317 vs. untreated cells, and identified histone 2 A and histone H4 as uniquely expressed proteins. These findings not only elucidate a novel role for LXR agonists in a model of CML, but demonstrate that mass fingerprints obtained by whole cell MALDI-TOF mass spectrometry effectively distinguish between treatment-induced cell phenotypes.

ObjectivesWe evaluated studies that used the World Health Organization’s (WHO) AirQ and AirQ+ tools for air pollution (AP) health risk assessment (HRA) and provided best practice suggestions for future assessments.MethodsWe performed a comprehensive review of studies using WHO’s AirQ and AirQ+ tools, searching several databases for relevant articles, reports, and theses from inception to Dec 31, 2022.ResultsWe identified 286 studies that met our criteria. The studies were conducted in 69 countries, with most (57%) in Iran, followed by Italy and India (∼8% each). We found that many studies inadequately report air pollution exposure data, its quality, and validity. The decisions concerning the analysed population size, health outcomes of interest, baseline incidence, concentration-response functions, relative risk values, and counterfactual values are often not justified, sufficiently. Many studies lack an uncertainty assessment.ConclusionOur review found a number of common shortcomings in the published assessments. We suggest better practices and urge future studies to focus on the quality of input data, its reporting, and associated uncertainties.

Albendazole (a benzimidazole) and ivermectin (a macrocyclic lactone) are the two most commonly co-administered anthelmintic drugs in mass-drug administration programs worldwide. Despite emerging resistance, we do not fully understand the mechanisms of resistance to these drugs nor the consequences of delivering them in combination. Albendazole resistance has primarily been attributed to variation in the drug target, a beta-tubulin gene. Ivermectin targets glutamate-gated chloride channels (GluCls), but it is unknown whether GluCl genes are involved in ivermectin resistance in nature. Using Caenorhabditis elegans, we defined the fitness costs associated with loss of the drug target genes singly or in combinations of the genes that encode GluCl subunits. We quantified the loss-of-function effects on three traits: (i) multi-generational competitive fitness, (ii) fecundity, and (iii) development. In competitive fitness and development assays, we found that a deletion of the beta-tubulin gene ben-1 conferred albendazole resistance, but ivermectin resistance required the loss of two GluCl genes (avr-14 and avr-15). The fecundity assays revealed that loss of ben-1 did not provide any fitness benefit in albendazole conditions and that no GluCl deletion mutants were resistant to ivermectin. Next, we searched for evidence of multi-drug resistance across the three traits. Loss of ben-1 did not confer resistance to ivermectin, nor did loss of any single GluCl subunit or combination confer resistance to albendazole. Finally, we assessed the development of 124 C. elegans wild strains across six benzimidazoles and seven macrocyclic lactones to identify evidence of multi-drug resistance between the two drug classes and found a strong phenotypic correlation within a drug class but not across drug classes. Because each gene affects various aspects of nematode physiology, these results suggest that it is necessary to assess multiple fitness traits to evaluate how each gene contributes to anthelmintic resistance.

School-based psychosocial interventions are increasingly put forward as a way to support young refugees’ and migrants’ well-being and mental health in resettlement. However, the evidence on these interventions’ effectiveness remains scarce and scholars denounce particular gaps in the evidence to date, pointing to a lack of large-scale, controlled studies and studies including social outcome measures. This cluster randomized study aims to strengthen the evidence base on school-based psychosocial interventions for refugee and migrant youth by assessing the effect of two interventions, Classroom Drama and Welcome to School, on youth’s mental health, resilience, and social relations in Belgium, Denmark, Norway, and the United Kingdom. Multilevel analyses were conducted separately for the two interventions (Classroom Drama, n = 307, ages 11-19; Welcome to School, n = 251, ages 11-23), using separate no-treatment control groups. Our analyses indicated a significant main, positive effect of Classroom Drama on perceived family support, and an effect on perceived support from friends that was moderated by country: in the United Kingdom, the intervention group reported an increase in perceived friend support, whereas the control group reported a decrease. Furthermore, baseline resilience moderated the effect of the Classroom Drama intervention on behavioral difficulties and well-being. No effects of Welcome to School on any of the outcome variables were found. Overall, this study provides novel, nuanced evidence on school-based psychosocial interventions for refugee and migrant adolescents.

Objectives To explore the associations of long-term exposure to air pollution with onset of all human health conditions.Design Prospective phenome-wide association study.Setting Denmark.Participants All Danish residents aged ≥30 years on 1 January 2000 were included (N=3 323 612). After exclusion of individuals with missing geocoded residential addresses, 3 111 988 participants were available for the statistical analyses.Main outcome measure First registered diagnosis of every health condition according to the International Classification of Diseases, 10th revision, from 2000 to 2017.Results Long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were both positively associated with the onset of more than 700 health conditions (ie, >80% of the registered health conditions) after correction for multiple testing, while the remaining associations were inverse or insignificant. As regards the most common health conditions, PM2.5 and NO2 were strongest positively associated with chronic obstructive pulmonary disease (PM2.5: HR 1.06 (95% CI 1.05 to 1.07) per 1 IQR increase in exposure level; NO2: 1.14 (95% CI 1.12 to 1.15)), type 2 diabetes (PM2.5: 1.06 (95% CI 1.05 to 1.06); NO2: 1.12 (95% CI 1.10 to 1.13)) and ischaemic heart disease (PM2.5: 1.05 (95% CI 1.04 to 1.05); NO2: 1.11 (95% CI 1.09 to 1.12)). Furthermore, PM2.5 and NO2 were both positively associated with so far unexplored, but highly prevalent outcomes relevant to public health, including senile cataract, hearing loss and urinary tract infection.Conclusions The findings of this study suggest that air pollution has a more extensive impact on human health than previously known. However, as this study is the first of its kind to investigate the associations of long-term exposure to air pollution with onset of all human health conditions, further research is needed to replicate the study findings.

Abstract Background Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. Methods Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. Results During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10–5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted

Abstract Pleistocene sea‐level change played a significant role in the evolution and assembly of island biotas. The formation of land bridges between islands during Quaternary glacial maxima, when sea levels were more than 120 metres below present‐day sea levels, often facilitated historical dispersal and gene flow between islands that are today geographically disconnected. Despite the importance of Pleistocene sea‐level change, few software packages exist that model the effects of this phenomenon in a standardised and generalised manner. Here, we present PleistoDist, an R package that allows users to visualise and quantify the effects of Pleistocene sea‐level change on islands over time, and test multiple temporally explicit hypotheses of inter‐island dispersal and community assembly. Re‐analysing published datasets, we demonstrate how using PleistoDist to account for historical sea‐level change can provide greater explanatory power when analysing extant island communities, and show how population genetic simulations can be used to generate spatiotemporally explicit neutral expectations of population genetic structure across island archipelagos.

IntroductionFederal agencies are increasingly expected to adopt enterprise risk management (ERM). However, public sector adoption of ERM has typically focused on the economic efficiency of tax-financed activities based on control-based practices. This reflects an emphasis on quantifiable concerns that invariably directs attention to risk, that (by definition) relates to identifiable and measurable events, thereby downplaying uncertain and unknown aspects of public exposures. This is a potentially serious shortcoming as government entities often act as society's risk managers of last resort. When extreme events happen what were previously considered private matters can quickly turn into public obligations. Hence, there is a need for proactive assessments of the evolving public risk landscape to discern unpredictable-even unknowable-developments.MethodsThe article reviews recent empirical studies on public risk management practices, effects of digitalization in public sector institutions, current strategic management research, and insights uncovered from a recent study of risk management practices in federal agencies. On this basis, the article explains how the ability to generate value from ERM can be enhanced when it intertwines with local responsive initiatives and central strategic risk analyses. It can form a dynamic adaptive risk management process where insights from dispersed actors inform updated risk analyses based on local autonomy and open exchange of information. This approach builds on specific structural features embedded in culture-driven aspirations to generate collaborative solutions. Its functional mode is an interactive control system with open discussions across levels and functions in contrast to conventional diagnostic controls that monitor predetermined key performance indicators (KPIs) and key risk indicators (KRIs).FindingsBacked by theoretical rationales and empirical research evidence, it is found that applications of ERM frameworks can produce positive results but is unable to deal with a public risk landscape characterized by uncertain unpredictable conditions with potentially extreme outcome effects. It is shown how interactive exchange of fast local insights and slow integrated strategic risk analyses supported by digitized data processing can form a dynamic adaptive system that enable public sector institutions to deal with emergent high-scale exposures. It is explained how the requirement for conducive organizational structures and supportive values require a new strategic risk leadership approach, which is contrasted to observed practices in federal agencies that are constrained by prevailing public governance requirements.DiscussionThe need to deal with uncertainty and unknown conditions demands a cognitive shift in current thinking from a primary focus on risk to also appraise complexity and prepare for the unexpected where data-driven methods can uncover emergent exposures through dynamic information processing. This requires strategic risk leaders that recognize the significance of complex public exposures with many unknowns and a willingness to facilitate digitalized information processing rooted in a collaborative organizational climate. If handled properly, adoption of ERM in public risk management can consider emergent dimensions in complex public exposures applying interactive information processing as a dynamic adaptive risk management approach incorporating digitized methods to solicit collective intelligence for strategic risk updating.

One of the primary obstacles in current cancer treatments lies in the extensive heterogeneity of genetic and epigenetic changes that occur in each arising tumour. However, an additional challenge persists, as certain types of cancer display shared immune deficiencies in the antigen processing machinery (APM). This includes the downregulation of human leukocyte antigen (HLA) class I molecules, which serve as peptide antigen receptors for T lymphocyte recognition that plays a crucial role in killing emerging tumours. Consequently, this contributes to immune escape in metastatic disease. Notably, current cell-based immunotherapies primarily focusing on T lymphocytes and the implementation of immune checkpoint inhibitor modalities have largely ignored the crucial task of reversing immune escape. This oversight may explain the limited success of these approaches becoming more effective cancer immunotherapies. Hence, there is a critical need to prioritize the discovery of new therapeutic candidates that can effectively address immune escape and synergize with evolving immunotherapy strategies. In this context, we identified curcuphenol in a cell-based screen from a library of marine extracts as a chemical entity that reverses the immune-escape phenotype of metastatic cancers. To advance these findings toward clinical efficacy, the present study describes the synthesis of analogues of naturally occurring curcuphenol with enhanced chemical properties and biological efficacy. Here we test the hypothesis that these curcuphenol analogues can evoke the power of the immune system to reduce the growth of metastatic disease in tumour bearing animals. Our findings indicate that these compounds effectively restore the expression of APM genes in metastatic tumours and inhibit the growth of highly invasive tumours in preclinical models, thereby counteracting the common immune evasion phenomenon observed in metastatic cancers. We conclude that cancer immunotherapies capable of boosting APM expression, hold great potential in maximizing the effectiveness of immune blockade inhibitors and eradicating invasive tumours.

Abstract Background Associations of birthweight, childhood body size and pubertal timing with breast cancer risks by menopausal status and tumor receptor subtypes are inconclusive. Thus, we investigated these associations in a population-based cohort of Danish women. Methods We studied 162,419 women born between 1930 and 1996 from the Copenhagen School Health Records Register. The register includes information on birthweight, measured childhood weights and heights at the age of 7–13 years, and computed ages at the onset of the growth spurt (OGS) and at peak height velocity (PHV). The Danish Breast Cancer Cooperative Group database provided information on breast cancer (n = 7510), including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and menopausal status. Hormone replacement therapy use came from the Danish National Prescription Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression. Results We found that birthweight was not associated with any breast cancer subtypes. While childhood BMI was not statistically significantly associated with ER+ tumors nor consistently with ER− tumors among pre-menopausal women, consistent inverse associations were found among postmenopausal women. At the age of 7 years, the HRs for postmenopausal ER+ and ER− tumors were 0.90 (95% CI 0.87–0.93) and 0.84 (95% CI 0.79–0.91) per BMI z-score, respectively. Similarly, childhood BMI was inversely associated with pre- and postmenopausal HER2− tumors, but not with HER2+ tumors. Childhood height was positively associated with both pre- and postmenopausal ER+ tumors, but not with ER− tumors. At the age of 7 years, the HRs for postmenopausal ER+ and ER− tumors were 1.09 (95% CI 1.06–1.12) and 1.02 (95% CI 0.96–1.09) per height z-score, respectively. In general, childhood height was positively associated with HER2+ and HER2− tumors among pre- and postmenopausal women. Ages at OGS and PHV were not associated with any breast cancer subtypes. Conclusions We showed that a high BMI and short stature in childhood are associated with reduced risks of certain breast cancer subtypes. Thus, childhood body composition may play a role in the development of breast cancer.

This article presents a reduced-order model of the highly turbulent wind turbine wake dynamics. The model is derived using a large eddy simulation (LES) database, which cover a range of different wind speeds. The model consists of several sub-models: (1) dimensionality reduction using proper orthogonal decomposition (POD) on the global database, (2) projection in modal coordinates to get time series of the dynamics, (3) interpolation over the parameter space that enables the prediction of unseen cases, and (4) stochastic time series generation to generalize the modal dynamics based on spectral analysis. The model is validated against an unseen LES case in terms of the modal time series properties as well as turbine performance and aero-elastic responses. The reduced-order model provides LES accuracy and comparable distributions of all channels. Furthermore, the model provides substantial insights about the underlying flow physics, how these change with respect to the thrust coefficient CT, and whether the model is constructed for single wake or deep array conditions. The predictive and stochastic capabilities of the reduced-order model can effectively be viewed as a generalization of a LES for statistically stationary flows, and the model framework can be applied to other flow cases than wake dynamics behind wind turbines.

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.

Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using

Wind farm flow control (WFFC) is a topic of interest at several research institutes and industry and certification agencies worldwide. For reliable performance assessment of the technology, the efficiency and the capability of the models applied to WFFC should be carefully evaluated. To address that, the FarmConners consortium has launched a common benchmark for code comparison under controlled operation to demonstrate its potential benefits, such as increased power production. The benchmark builds on available data sets from previous field campaigns, wind tunnel experiments, and high-fidelity simulations. Within that database, four blind tests are defined and 13 participants in total have submitted results for the analysis of single and multiple wakes under WFFC. Here, we present Part I of the FarmConners benchmark results, focusing on the blind tests with large-scale rotors. The observations and/or the model outcomes are evaluated via direct power comparisons at the upstream and downstream turbine(s), as well as the power gain at the wind farm level under wake steering control strategy. Additionally, wake loss reduction is also analysed to support the power performance comparison, where relevant. The majority of the participating models show good agreement with the observations or the reference high-fidelity simulations, especially for lower degrees of upstream misalignment and narrow wake sector. However, the benchmark clearly highlights the importance of the calibration procedure for control-oriented models. The potential effects of limited controlled operation data in calibration are particularly visible via frequent model mismatch for highly deflected wakes, as well as the power loss at the controlled turbine(s). In addition to the flow modelling, the sensitivity of the predicted WFFC benefits to the turbine representation and the implementation of the controller is also underlined. The FarmConners benchmark is the first of its kind to bring a wide variety of data sets, control settings, and model complexities for the (initial) assessment of farm flow control benefits. It forms an important basis for more detailed benchmarks in the future with extended control objectives to assess the true value of WFFC.

The power performance of a wind turbine in complex terrain is studied by means of large eddy simulations (LESs). The simulations show that the turbine performance is significantly different compared to what should be expected from the available wind. The reason for this deviation is that the undisturbed flow field behind the turbine is non-homogeneous and therefore results in a very different wake development and induction than seen for a turbine in flat homogeneous terrain.

Climate warming and the resulting acceleration of freshwater discharge from the Greenland Ice Sheet are impacting Arctic marine coastal ecosystems, with implications for their biological productivity. To accurately project the future of coastal ecosystems and place recent trends into perspective, palaeo-records are essential. Here, we show runoff estimates from the late 19th century to the present day for a large sub-Arctic fjord system (Nuup Kangerlua, southwest Greenland) influenced by both marine- and land-terminating glaciers. We followed a multiproxy approach to reconstruct spatial and temporal trends in primary production from four sediment core records, including diatom fluxes and assemblage composition changes and biogeochemical and sedimentological proxies (total organic carbon, nitrogen, C/N ratio, biogenic silica, δ13C, δ15N, and grain-size distribution). We show that an abrupt increase in freshwater runoff in the mid-1990s was reflected by a 3-fold increase in biogenic silica fluxes in the glacier-proximal area of the fjord. In addition to increased productivity, freshwater runoff modulates the diatom assemblages and drives the dynamics and magnitude of the diatom spring bloom. Our records indicate that marine productivity is higher today than it has been at any point since the late 19th century and suggest that increased mass loss of the Greenland Ice Sheet may continue promoting high productivity levels at sites proximal to marine-terminating glaciers. We highlight the importance of palaeo-records in offering a unique temporal perspective on ice–ocean–ecosystem responses to climate forcing beyond existing remote sensing or monitoring time series.

This article investigates school belonging among migrant students and how this changed during the Covid‐19 pandemic. Drawing on quantitative data gathered from 751 migrant students in secondary schools in six European countries (Belgium, Denmark, Finland, Norway, Sweden, and the UK), we examined the impact of Covid‐19 school closures, social support, and post‐traumatic stress symptoms on changes in school belonging. Linear regression showed a non‐significant decrease in school belonging, and none of the studied variables had a significant effect on this change in our whole sample. However, sensitivity analysis on a subsample from three countries (Denmark, Finland, and the UK) showed a small but significant negative effect of increasing post‐traumatic stress symptoms on school belonging during Covid‐19 school closures. Given that scholarship on school belonging during Covid‐19 is emergent, this study delineates some key areas for future research on the relationship between wellbeing, school belonging, and inclusion.

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

Colorful signals in nature provide some of the most stunning examples of rapid phenotypic evolution. Yet, studying color pattern evolution has been historically difficult owing to differences in perceptual ability of humans and analytical challenges with studying how complex color patterns evolve. Island systems provide a natural laboratory for testing hypotheses about the direction and magnitude of phenotypic change. A recent study found that plumage colors of island species are darker and less complex than continental species. Whether such shifts in plumage complexity are associated with increased rates of color evolution remains unknown. Here, we use geometric morphometric techniques to test the hypothesis that plumage complexity and insularity interact to influence color diversity in a species-rich clade of colorful birds—kingfishers (Aves: Alcedinidae). In particular, we test three predictions: (1) plumage complexity enhances interspecific rates of color evolution, (2) plumage complexity is lower on islands, and (3) rates of plumage color evolution are higher on islands. Our results show that more complex plumages result in more diverse colors among species and that island species have higher rates of color evolution. Importantly, we found that island species did not have more complex plumages than their continental relatives. Thus, complexity may be a key innovation that facilitates evolutionary response of individual color patches to distinct selection pressures on islands, rather than being a direct target of selection itself. This study demonstrates how a truly multivariate treatment of color data can reveal evolutionary patterns that might otherwise go unnoticed.

Objectives: Pilot assessment of an equine-assisted services intervention for Veterans with posttraumatic stress disorder. Design: Prospective cohort. Setting: A large Veterans Administration healthcare system. Intervention: Two sessions of instruction in horsemanship skills and two sessions of trail rides. Main outcome measures: Safety and feasibility of recruitment, retention, providing the intervention, and measuring outcomes, as well as acceptability of the intervention to the population studied were the main outcome measures. Results: There were no injuries among the 18 participants, 6 staff, or 11 equines over the 3 months of the study. Eleven of 12 (92 %) planned intervention sessions were provided, with one being canceled due to weather. Out of approximately 1800 potential subjects, 21 were enrolled within three months and three dropped out before the first session. The mean number of sessions attended was 3 % and 52 % of participants completed all sessions. The mean PACES score for all sessions together was 109 (SD = 12), with a range of 50–126. Pre- to one-month post-intervention exploratory results indicated increased psychological flexibility (p = 0.008) and positive affect (p = 0.008) as measured by the Acceptance and Action Questionnaire II and the Positive and Negative Affect Scale, respectively as well as decreased PTSD (p = 0.001) and depressive symptoms (p = 0.017) as measured by the PTSD Checklist for DSM 5 and the Beck Depression Inventory, respectively. Conclusions: Results suggest the intervention can be conducted with minimal risk. Further, it was feasible to recruit participants as well as provide the intervention and measure exploratory outcomes. Session attendance and PACES scores indicate acceptability to the Veteran population. The exploratory results will provide sample size estimates for future randomized controlled studies of this intervention Future studies should plan for missed sessions due to weather and consider compensating subjects to enhance retention. Finally, this work provides preliminary evidence that this intervention, without a mental health treatment component, might benefit the mental health of Veterans with PTSD.

Introduction Cigarette smoking prevalence is significantly higher among people with mental health problems than among the general population. Smoking accounts for much of the reduction in life expectancy associated with mental illness, why the high co-occurrence of smoking and mental health illness is a major public health concern. Persons belonging to socioeconomical disadvantaged groups have higher risk of mental health conditions and also higher smoking rates. Objectives In this study we aim to examine smoking trajectories among adult smokers between 2012 and 2020. Furthermore, we aim to investigate differences in smoking trajectories by adult depression by taking into consideration participants intergenerational socioeconomic mobility (ISEM). Methods Analyses were based on data from CONSTANCES, a French general population cohort conducted from 2012 to 2020. In total were 107,734 participants included after exclusion of never smokers. Depression was measured by the CES-D scale, and depression was classified with a score ≥16. ISEM is based on childhood (maternal and parental occupational grade) and adult socioeconomic position (SEP), and low ISEM includes those with low SEP as child and adult and high ISEM those with consistent high SEP. Group-based trajectories modelling (GBTM) was used to determine smoking status trajectories. To address the association between ISEM and smoking trajectory class we used multinomial logistic regression with former smokers as reference class adjusted for depression, household income, sex and age. Results We identified five smoking trajectories 1) Former smokers (56.6%), 2) Long-term smokers (26.4%), 3) Intermediate smokers (3.3%), 4) Early quitters (5.0%) and 5) Late quitters (8.7%). Preliminary results from multinomial logistic regression showed that persons with low ISEM had higher odds of depression (OR [95%CI]=1.91 [1.77;2.06]) than those with high ISEM. Participants with low ISEM had higher odds of being long-term smoking than former smokers compared to those with high ISEM (ORa [95%CI]=1.55 [1.43;1.67]). Furthermore, those with low ISEM had lower odds of being in any of the other smoking trajectory groups vs. former smokers compared to those with high ISEM (ORa [95%CI]=0.82 [0.69;0.97]) for intermediate smokers, ORa [95%CI]=0.75 [0.66;0.85]) for early quitters, and ORa [95%CI]=0.78 [0.70;0.87]) for late quitters). Conclusions Preliminary results showed an association between ISEM and smoking trajectories in our study. Persons with low ISEM are more likely to be long-term smokers. Future analysis should consider the effect of depression as a mediating factor on the association between ISEM and smoking trajectories. Disclosure of Interest None Declared

Emerging cancers are sculpted by neo-Darwinian selection for superior growth and survival but minimal immunogenicity; consequently, metastatic cancers often evolve common genetic and epigenetic signatures to elude immune surveillance. Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery (APM) that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Fascinating ethnographic and experimental findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty. Here, we screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules such as Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in a wide variety of metastatic tumours that subsequently sensitizing tumours to T lymphocyte recognition. Remarkably, H3K27Ac ChIPseq analysis established that cannabigerol and gamma interferon induce overlapping epigenetic signatures and key gene pathways in metastatic tumours related to cellular senescence, as well as APM genes involved in revealing metastatic tumours to the adaptive immune response. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease. Finally, the fundamental discovery of the ability of cannabinoids to alter epigenetic programs may help elucidate many of the pleiotropic medicinal effects of cannabinoids on human physiology.

Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson’s Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10−5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.

Background: The majority of studies have shown higher greenness exposure associated with reduced mortality risks, but few controlled for spatially correlated air pollution and traffic noise exposures. We aim to address this research gap in the ELAPSE pooled cohort. Methods: Mean Normalized Difference Vegetation Index (NDVI) in a 300-m grid cell and 1-km radius were assigned to participants’ baseline home addresses as a measure of surrounding greenness exposure. We used Cox proportional hazards models to estimate the association of NDVI exposure with natural-cause and cause-specific mortality, adjusting for a number of potential confounders including socioeconomic status and lifestyle factors at individual and area-levels. We further assessed the associations between greenness exposure and mortality after adjusting for fine particulate matter (PM2.5), nitrogen dioxide (NO2) and road traffic noise. Results: The pooled study population comprised 327,388 individuals who experienced 47,179 natural-cause deaths during 6,374,370 person-years of follow-up. The mean NDVI in the pooled cohort was 0.33 (SD 0.1) and 0.34 (SD 0.1) in the 300-m grid and 1-km buffer. In the main fully adjusted model, 0.1 unit increment of NDVI inside 300-m grid was associated with 5% lower risk of natural-cause mortality (Hazard Ratio (HR) 0.95 (95% CI: 0.94, 0.96)). The associations attenuated after adjustment for air pollution [HR (95% CI): 0.97 (0.96, 0.98) adjusted for PM2.5; 0.98 (0.96, 0.99) adjusted for NO2]. Additional adjustment for traffic noise hardly affected the associations. Consistent results were observed for NDVI within 1-km buffer. After adjustment for air pollution, NDVI was inversely associated with diabetes, respiratory and lung cancer mortality, yet with wider 95% confidence intervals. No association with cardiovascular mortality was found. Conclusions: We found a significant inverse association between surrounding greenness and natural-cause mortality, which remained after adjusting for spatially correlated air pollution and traffic noise.

Background: The association between long-term exposure to air pollution and mortality from cardiorespiratory diseases is well established, yet the evidence for other diseases remains limited. Objectives: To examine the associations of long-term exposure to air pollution with mortality from diabetes, dementia, psychiatric disorders, chronic kidney disease (CKD), asthma, acute lower respiratory infection (ALRI), as well as mortality from all-natural and cardiorespiratory causes in the Danish nationwide administrative cohort. Methods: We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (warm season) were estimated using European-wide hybrid land-use regression models (100 m × 100 m) and assigned to baseline residential addresses. We used Cox proportional hazard models to evaluate the association between air pollution and mortality, accounting for demographic and socioeconomic factors. We additionally applied indirect adjustment for smoking and body mass index (BMI). Results: During 47,023,454 person-years of follow-up, 803,881 people died from natural causes. Long-term exposure to PM2.5 (mean: 12.4 µg/m3), NO2 (20.3 µg/m3), and/or BC (1.0 × 10-5/m) was statistically significantly associated with all studied mortality outcomes except CKD. A 5 µg/m3 increase in PM2.5 was associated with higher mortality from all-natural causes (hazard ratio 1.11; 95% confidence interval 1.09–1.13), cardiovascular disease (1.09; 1.07–1.12), respiratory disease (1.11; 1.07–1.15), lung cancer (1.19; 1.15–1.24), diabetes (1.10; 1.04–1.16), dementia (1.05; 1.00–1.10), psychiatric disorders (1.38; 1.27–1.50), asthma (1.13; 0.94–1.36), and ALRI (1.14; 1.09–1.20). Associations with long-term exposure to ozone (mean: 80.2 µg/m3) were generally negative but became significantly positive for several endpoints in two-pollutant models. Generally, associations were attenuated but remained significant after indirect adjustment for smoking and BMI. Conclusion: Long-term exposure to PM2.5, NO2, and/or BC in Denmark were associated with mortality beyond cardiorespiratory diseases, including diabetes, dementia, psychiatric disorders, asthma, and ALRI.

The actuator line method is a widely used technique to model wind turbines in computational fluid dynamics, as it significantly reduces the required computational expense in comparison to simulations using geometrically resolved blades. Actuator line coupled to an aeroelastic solver enables not only the study of detailed wake dynamics but also aeroelastic loads, flexible blade deformation and how this interacts with the flow. Validating aeroelastic actuator line predictions of blade loading, deflection and turbine wakes in complex inflow scenarios is particularly relevant for modern turbine designs and wind farm studies involving realistic inflows, wind shear or yaw misalignment. This work first implements a vortex-based smearing correction in an aeroelastic coupled actuator line, and performs a grid resolution and smearing parameter study which demonstrates significant improvement in the blade loading and in the numerical dependencies of predicted thrust and power output. A validation is then performed using a 2.3 MW turbine with R = 40 m radius, comparing against blade resolved fluid-structure interaction simulations and full-scale measurement data, in both laminar and turbulent inflows including both high shear and high yaw misalignment. For an axisymmetric laminar inflow case, the agreement between blade resolved and actuator line simulations is excellent, with prediction of integrated quantities within 0.2%. In more complex flow cases, good agreement is seen in overall trends but the actuator line predicts lower blade loading and flapwise deflection, leading to underpredictions of thrust by between 5.3% and 8.4%. The discrepancies seen can be attributed to differences in wake flow, induction, the reliance of the actuator line on the provided airfoil data and the force application into the computational domain. Comparing the wake between coupled actuator line and blade resolved simulations for turbulent flow cases also shows good agreement in wake deficit and redirection, even under high yaw conditions. Overall, this work validates the implementation of the vortex-based smearing correction and demonstrates the ability of the actuator line to closely match blade loading and deflection predictions of blade resolved simulations in complex flows, at a significantly lower computational cost.

Lipid metabolism contributes to the regulation of leukocyte activity and immune responses, and may serve as a therapeutic target in the pathophysiology and clinical management of autoimmune disorders. In addition to lipid-lowering properties, statins have been shown to exert anti-inflammatory and immunomodulatory effects within the context of autoimmunity. Importantly, autoimmune incidence and lipid markers differ between men and women, suggesting that the relationship between lipid metabolism and immune function may vary by sex. Therefore, we investigated whether a predictive, sex-specific relationship exists between serum lipids, statin use, and antinuclear antibodies (ANA)—a routine clinical marker of autoimmunity and immune dysfunction—in U.S. men and women (>20 years old; n = 1,526) from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Within this population, a greater proportion of women were positive for ANA (ANA+) and had higher ANA titers, as compared to men. While we did not observe statistical differences in average total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), or triglyceride levels in ANA positive (ANA+) vs. ANA negative (ANA–) men or women, we observed that a greater proportion of ANA+ women had high total cholesterol levels (>240 mg/dL) when compared to ANA+ men (13.0 vs. 9.0%), and that a greater percentage of ANA+ women had low HDL-C as compared to ANA+ men (29.2 vs. 19.6%). However, in logistic regression models, total cholesterol, LDL-C, and HDL-C levels were not able to predict ANA status, whereas elevated serum triglycerides (150 to < 200 mg/dL) were significantly less likely to be ANA+ vs. ANA– (OR 0.33; 95% CI 0.11–0.92) in men only. Interestingly, women who reported taking statins have significantly lower odds of being ANA+ (OR 0.25; 95% CI 0.09–0.76), whereas no significant association between statin use and ANA status was observed in men. Together, our findings provide novel insight into the relationship between lipid metabolism and autoimmunity by elucidating the limited, albeit sex-specific utility of routine clinical serum lipid levels to predict ANA status at the population level, while further identifying a sex-specific and protective role for statins in predicting ANA status in women.

Strategies to combat COVID-19 include vaccines and Monoclonal Antibody Therapy. While vaccines aim to prevent development of symptoms, Monoclonal Antibody Therapy aims to prevent the progression of mild to severe disease. An increasing number of COVID-19 infections in vaccinated patients raised the question of whether vaccinated and unvaccinated COVID-19 positive patients respond differently to Monoclonal Antibody Therapy. The answer can help prioritize patients if resources are scarce. We performed a retrospective study to evaluate and compare the outcomes and risks for disease progression between vaccinated and unvaccinated COVID-19 patients treated with Monoclonal Antibody Therapy by measuring the number of Emergency Department visits and hospitalizations within 14 days as well as the progression to severe disease, defined through the Intensive Care Unit admissions within 14 days, and death within 28 days from the Monoclonal Antibody infusion. From 3898 included patients, 2009 (51.5%) were unvaccinated at the time of Monoclonal Antibody infusion. Unvaccinated patients had more Emergency Department visits (217 vs. 79, p < 0.0001), hospitalizations (116 vs. 38, p < 0.0001), and progression to severe disease (25 vs. 19, p = 0.016) following treatment with Monoclonal Antibody Therapy. After adjustment for demographics and comorbidities, unvaccinated patients were 2.45 times more likely to seek help in the Emergency Department and 2.70 times more likely to be hospitalized. Our data suggest the added benefit between the COVID-19 vaccine and Monoclonal Antibody Therapy.

Gonioridleylactam (1), a new compound, is a unique dimeric aristolactam isolated from the EtOAc extract of the twigs of Goniothalamus ridleyi King. The structure of gonioridleylactam (1) consists of two different aristolactams linked together with two methylenedioxy bridges at C–3/C–3′ and C–4/C–4′, generating a ten-membered ring of [1,3,6,8]tetraoxecine. A new natural product, gonioridleyindole (3-hydroxymethyl-1-methyl-1H-benz[f]indole-4,9-dione, 2), together with eight known compounds (3–10) were also isolated from this plant. Their structures were extensively characterized by spectroscopic methods and comparisons were made with the literature. Compounds 1–4, 7, and 9 were evaluated for their α-glucosidase inhibitory activity. Of these, 3,5-demethoxypiperolide (7) displayed the highest α-glucosidase inhibitory activity, with an IC50 value of 1.25 µM.