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Background To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt‐1 (soluble Fms‐like tyrosine kinase‐1), PlGF (placental growth factor), or their impact on birthweight. Methods and Results sFlt‐1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt‐1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt‐1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester‐related variation in levels of sFlt‐1 and PlGF, after correction for relevant confounders, the sFlt‐1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt‐1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54–26.29], P=0.79; sFlt‐1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73–22.50], P=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P=0.03), and sFlt‐1 displayed a negative correlation with birthweight (r=−0.462, P

Abstract Metabolic acidosis unfavourably influences the nutritional status of patients with non‐dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta‐analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta‐analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m2, and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl‐binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid‐arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P

Abstract Stage‐based demographic methods, such as matrix population models (MPMs), are powerful tools used to address a broad range of fundamental questions in ecology, evolutionary biology and conservation science. Accordingly, MPMs now exist for over 3000 species worldwide. These data are being digitised as an ongoing process and periodically released into two large open‐access online repositories: the COMPADRE Plant Matrix Database and the COMADRE Animal Matrix Database. During the last decade, data archiving and curation of COMPADRE and COMADRE, and subsequent comparative research, have revealed pronounced variation in how MPMs are parameterized and reported. Here, we summarise current issues related to the parameterisation and reporting of MPMs that arise most frequently and outline how they affect MPM construction, analysis, and interpretation. To quantify variation in how MPMs are reported, we present results from a survey identifying key aspects of MPMs that are frequently unreported in manuscripts. We then screen COMPADRE and COMADRE to quantify how often key pieces of information are omitted from manuscripts using MPMs. Over 80% of surveyed researchers (n = 60) state a clear benefit to adopting more standardised methodologies for reporting MPMs. Furthermore, over 85% of the 300 MPMs assessed from COMPADRE and COMADRE omitted one or more elements that are key to their accurate interpretation. Based on these insights, we identify fundamental issues that can arise from MPM construction and communication and provide suggestions to improve clarity, reproducibility and future research utilising MPMs and their required metadata. To fortify reproducibility and empower researchers to take full advantage of their demographic data, we introduce a standardised protocol to present MPMs in publications. This standard is linked to www.compadre‐db.org, so that authors wishing to archive their MPMs can do so prior to submission of publications, following examples from other open‐access repositories such as DRYAD, Figshare and Zenodo. Combining and standardising MPMs parameterized from populations around the globe and across the tree of life opens up powerful research opportunities in evolutionary biology, ecology and conservation research. However, this potential can only be fully realised by adopting standardised methods to ensure reproducibility.

Background Inhibition of prostaglandin synthesis by nonsteroidal anti‐inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney‐derived PGE2 production. Methods and Results PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population‐based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross‐sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR

Abstract Climate change is intensifying the fire regime across Siberia, with the potential to alter carbon combustion and post‐fire carbon re‐accumulation trajectories. Few field‐based estimates of fire severity (e.g., carbon combustion and tree mortality) exist in Siberian larch forests (Larix spp.), which limits our ability to project how an intensified fire regime will affect regional and global climate feedbacks. Here, we present field‐based estimates of fire‐induced tree mortality and carbon loss in eastern Siberian larch forests. Our results suggest that fires in this region result in high tree mortality (means of 83% and 76% at Arctic and subarctic sites, respectively). In both absolute and relative terms, aboveground carbon loss following fire is higher in Siberian larch forests than in North America, but belowground carbon loss is considerably lower. This suggests fundamental differences in wildfire behavior and carbon dynamics between dominant vegetation types across the boreal biome.

Abstract Objective STXBP1‐related disorders are rare genetic epilepsies and neurodevelopmental disorders, but the impact of symptoms across clinical domains is poorly understood. Disease concept models are formal frameworks to assess the lived experience of individuals and their families and provide a basis for generating outcome measures. Methods We conducted semistructured, qualitative interviews with 19 caregivers of 16 individuals with STXBP1‐related disorders and 7 healthcare professionals. We systematically coded themes using NVivo software and grouped concepts into the domains of symptoms, symptom impact, and caregiver impact. We quantified the frequency of concepts throughout the lifespan and across clinical subgroups stratified by seizure history and developmental trajectories. Results Over 25 hours of interviews, we coded a total of 3626 references to 38 distinct concepts. In addition to well‐recognized clinical features such as developmental delay (n = 240 references), behavior (n = 201), and seizures (n = 147), we identified previously underrepresented symptoms including gastrointestinal (n = 68) and respiratory symptoms (n = 24) and pain (n = 30). The most frequently referenced symptom impacts were autonomy (n = 96), socialization (n = 64), and schooling (n = 61). Emotional impact (n = 354), support (n = 200), and daily life & activities (n = 108) were highly cited caregiver impacts. We found that seizures were more commonly referenced in infancy than in other age groups, while behavior and socialization were more likely to be referred to in childhood. We found that caregivers of individuals with ongoing seizures were less likely to reference developmental delay, possibly due to the relatively high impact of seizures. Significance STXBP1‐related disorders are complex conditions affecting a wide range of clinical and social domains. We comprehensively mapped symptoms and their impact on families to generate a comprehensive disease model as a foundation for clinical endpoints in future trials.

Abstract Background Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low. Patients and Methods This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet‐lymphocyte‐ratio (NLR and PLR). Programmed death‐ligand 1 (PD‐L1) expression was determined on residual material. Cachexia was defined according to Fearon et al. (2011). Skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were evaluated on computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analyses were performed for 6 months progression free survival (PFS6m) and overall survival (OS). Results Significant early weight loss (>2%) during the first 6 weeks of therapy was shown in 34 patients (35%). This patient subgroup had a significantly higher NLR and PLR at baseline. NLR and PLR were inversely correlated with SM and VAT index. Independent predictors of PFS6m were lower World Health Organization performance status (HR 0.16 [0.04–0.54] p = 0.003), higher baseline SAT index (HR 1.045 [1.02–1.08] p = 0.003), and weight loss 2% early weight loss remained a predictor of OS, independent of PD‐L1 expression (HR 2.09 [1.11–3.92] p = 0.02, HR 2.18 [1.13–4.21] p = 0.02). Conclusion We conclude that the combination of cachexia at baseline and weight loss during ICI therapy is associated with worse OS in R/M HNSCC patients, independent of PD‐L1 expression.

Abstract Understanding where, when, and why agroecosystems are changing requires quality information about ecosystems that span land tenure, ecological processes, and spatial scales. Over the past two decades, land management agencies and research groups have adopted a suite of standardized methods for monitoring rangelands, which have been implemented at over 85,000 monitoring locations globally. However, the ability to use these data to understand agroecosystem dynamics and change across scales and across land ownership has been limited because, until now, these data have not been available in a harmonized, accessible format for analyses, modeling, and decision‐support tools. We present the Landscape Data Commons, a cyberinfrastructure platform that harmonizes and aggregates standardized agroecosystem data, enables linkages to models, and facilitates analysis and interpretation of data within decision‐support tools. The Landscape Data Commons provides a community platform for users to contribute data and develop next‐generation tools to support agroecosystem management through the 21st century.

Abstract Long ncRNAs (lncRNAs) have been shown to play a biological and physiological role in various tissues including the heart. We and others have previously established that the lncRNA Oip5os1 (1700020I14Rik, OIP5‐AS1, Cyrano) is enriched in striated muscles, and its deletion in mice leads to defects in both skeletal and cardiac muscle function. In the present study, we investigated the impact of global Oip5os1 deletion on cardiac function in the setting of streptozotocin (STZ)‐induced diabetes. Specifically, we studied male WT and KO mice with or without diabetes for 24 weeks, and phenotyped animals for metabolic and cardiac endpoints. Independent of genotype, diabetes was associated with left ventricular diastolic dysfunction based on a fall in E'/A' ratio. Deletion of Oip5os1 in a setting of diabetes had no significant impact on ventricular function or ventricular weight, but was associated with left atrial dysfunction (reduced fractional shortening) and myopathy which was associated with anesthesia intolerance and premature death in the majority of KO mice tested during cardiac functional assessment. This atrial phenotype was not observed in WT diabetic mice. The most striking molecular difference was a reduction in the metabolic regulator ERRalpha in the atria of KO mice compared with WT mice. There was also a trend for a reduction in Serca2a. These findings highlight Oip5os1 as a gene of interest in aspects of atrial function in the setting of diabetes, highlighting an additional functional role for this lncRNA in cardiac pathological settings.

Abstract Animal movement is the mechanism connecting landscapes to fitness, and understanding variation in seasonal animal movements has benefited from the analysis and categorization of animal displacement. However, seasonal movement patterns can defy classification when movements are highly variable. Hidden Markov movement models (HMMs) are a class of latent‐state models well‐suited to modeling movement data. Here, we used HMMs to assess seasonal patterns of variation in the movement of pronghorn (Antilocapra americana), a species known for variable seasonal movements that challenge analytical approaches, while using a population of mule deer (Odocoileus hemionus), for whom seasonal movements are well‐documented, as a comparison. We used population‐level HMMs in a Bayesian framework to estimate a seasonal trend in the daily probability of transitioning between a short‐distance local movement state and a long‐distance movement state. The estimated seasonal patterns of movements in mule deer closely aligned with prior work based on indices of animal displacement: a short period of long‐distance movements in the fall season and again in the spring, consistent with migrations to and from seasonal ranges. We found seasonal movement patterns for pronghorn were more variable, as a period of long‐distance movements in the fall was followed by a winter period in which pronghorn were much more likely to further initiate and remain in a long‐distance movement pattern compared with the movement patterns of mule deer. Overall, pronghorn were simply more likely to be in a long‐distance movement pattern throughout the year. Hidden Markov movement models provide inference on seasonal movements similar to other methods, while providing a robust framework to understand movement patterns on shorter timescales and for more challenging movement patterns. Hidden Markov movement models can allow a rigorous assessment of the drivers of changes in movement patterns such as extreme weather events and land development, important for management and conservation.

Abstract NASA's InSight has detected a large magnitude seismic event, labeled S1222a. The event has a moment magnitude of MWMa4.7, with five times more seismic moment compared to the second largest event. The event is so large that features are clearly observed that were not seen in any previously detected events. In addition to body phases and Rayleigh waves, we also see Love waves, minor arc surface wave overtones, and multi‐orbit surface waves. At long periods, the coda event exceeds 10 hr. The event locates close to the North‐South dichotomy and outside the tectonically active Cerberus Fossae region. S1222a does not show any evident geological or tectonic features. The event is extremely rich in frequency content, extending from below 1/30 Hz up to 35 Hz. The event was classified as a broadband type event; we also observe coda decay and polarization similar to that of very high frequency type events.

Abstract Elephants frequently raid crops within their ranges in Africa and Asia. These raids can greatly impact agricultural productivity and food security for farmers. Therefore, there is a need to explore cost‐effective measures that would reduce the susceptibility of crops and agricultural fields to elephant raiding, and further promote sustainable human–elephant coexistence. Previous studies have examined the susceptibility of crop fields to elephant raids using field characteristics such as field size and proximity to water sources. However, there are limited studies investigating how different crop types, individually and in their combinations, influence crop susceptibility to elephant raiding. This study utilized data collected from crop fields raided by the African savanna elephant (Loxodonta africana) between 2008 and 2018 in the eastern Okavango Panhandle, northern Botswana. Data on crops grown, number of crop‐raiding incidences for each crop, and elephant raiding incidences were recorded for each field assessed. Incidence risks (IR) and field risk value (RV) were computed using an adaptive epidemiological approach. The results showed that elephant raiding incidents varied significantly amongst crop types over space and time (p

Abstract Objective Healthcare systems, specifically operating rooms, significantly contribute to greenhouse gas emissions. Addressing operating room environmental sustainability requires understanding current practices, opinions, and barriers. This is the first study assessing the attitudes and perceptions of otolaryngologists on environmental sustainability. Study Design Cross‐sectional virtual survey. Setting Email survey to active members of the Canadian Society of Otolaryngology–Head and Neck Surgery. Methods A 23‐question survey was developed in REDCap. The questions focused on four themes: (1) demographics, (2) attitudes and beliefs, (3) institutional practices, and (4) education. A combination of multiple choice, Likert‐scale, and open‐ended questions were employed. Results Response rate was 11% (n = 80/699). Most respondents strongly believed in climate change (86%). Only 20% strongly agree that operating rooms contribute to the climate crisis. Most agree environmental sustainability is very important at home (62%) and in their community (64%), only 46% said it was very important in the operating room. Barriers to environmental sustainability were incentives (68%), hospital supports (60%), information/knowledge (59%), cost (58%), and time (50%). Of those involved in residency programs, 89% (n = 49/55) reported there was no education on environmental sustainability or they were unsure if there was. Conclusion Canadian otolaryngologists strongly believe in climate change, but there is more ambivalence regarding operating rooms as a significant contributor. There is a need for further education and a systemic reduction of barriers to facilitate eco‐action in otolaryngology operating rooms.

Abstract Background The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. Methods We analyzed two population‐based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population‐based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. Results A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12–1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42–1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon–rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. Conclusions The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow‐up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

Abstract Despite the demonstrated effectiveness of vaccines, varying levels of hesitancy were observed among healthcare and long‐term care workers, who were prioritized in the roll out of COVID‐19 vaccines due to their high risk of exposure to SARS‐CoV‐2 transmission. However, the evidence around the measurable impact of various educational interventions to improve vaccine confidence is limited. The proposed scoping review is intended to explore any emerging research and experiences of delivering educational interventions to improve COVID‐19 vaccine confidence among health and long‐term care workforces. We aim to identify characteristics of both informal and formal educational interventions delivered during the pandemic to support COVID‐19 vaccine hesitancy. Using the guidance outlined by the Joanna Briggs Institute, we intend to search five databases including, Ovid MEDLINE and Web of Science, as well as grey literature. We will consider all study designs and reports in an effort to include a breadth of sources to ensure our review will capture preliminary evidence, as well as more exploratory experiences of COVID‐19 vaccine education delivery. Articles will be screened by three reviewers independently and the data will be charted, and results described narratively.

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long‐term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost‐of‐illness analysis with a bottom‐up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events—European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12‐month follow‐up in 2020 Euros. We estimated a disability weight for the 12‐month post‐PE status and corresponding disability adjusted life years presumably owing to PE. Disease‐specific costs in the first year of follow‐up after an incident PE case ranged between 9135 Euros and 10 620 Euros. The proportion of indirect costs was 42% to 49% of total costs. Costs were lowest in patients with ongoing cancer, mainly because productivity loss was less evident in this already burdened population. The calculated disability weight for survivors who were cancer free 12 months post‐PE was 0.017, and the estimated disability adjusted life years per incident case were 1.17. Conclusions The economic burden imposed by PE to society and affected patients is considerable, and productivity loss is its main driver. The disease burden from PE is remarkable and translates to the loss of roughly 1.2 years of healthy life per incident PE case.

Abstract Background Nail salon workers (NSW) in the United States (U.S.) are predominantly immigrant women who face a number of occupational hazards, such as biological, ergonomic, and chronic chemical exposures. Additionally, there are challenges to keeping up with the latest practices in this evolving small business industry. Licensure requirements are intended to keep not only consumers but also workers safe, however licensure requirements vary between states creating little skill, education, and occupational health and safety knowledge and practice consistency among the nail salon workforce. The current state of nail salons and licensure of workers in the State of Michigan—an overlooked state and region (Midwest) in NSW research—was determined to better characterize this workforce. Methods A Freedom of Information Act request was submitted to the Michigan Department of Licensing and Regulatory Affairs regarding nail salon establishments and their workers, formally termed manicurists, and citation data for breaches. Data were provided on the number of licensed cosmetologists and cosmetology businesses from January 2017 to March 2021. From there, the total number of licensed manicurists was determined, and the cosmetology establishment list was analyzed to see if the businesses exclusively or predominantly provided nail services. Results As of Mach 2021, there were 1372 nail salons that exclusively provided nail services and over 12,000 licensed manicurists. Over half of the disciplinary actions cited were for salons not officially licensed. Michigan has reduced licensure requirements compared to other states and no continuing education (CE) requirements for license renewals. Conclusion There is a need for industry educational and training standardization, across the nation, as well as heightened licensure requirements for these vulnerable workers. CE not only keeps workers abreast of the latest practices in the industry, but also provides them the skills and knowledge to enhance their worker health, safety, and wellbeing.

Background Consensus lacks concerning a bidirectional association between kidney function and atrial fibrillation (AF), but this is crucial information for prevention/treatment efforts for both chronic kidney disease and AF. Therefore, we investigated the bidirectional association between kidney function and AF. Methods and Results This study was a prospective cohort study including 9228 participants (mean age, 64.9 years; 57.2% women) with information on kidney function (estimated glomerular filtration rate [eGFR] based on serum creatinine [eGFRcreat], cystatin C [eGFRcys], or both [eGFRcreat‐cys], and urine albumin‐to‐creatinine ratio) and AF. Reduced kidney function was defined as eGFRcreat

Abstract The “learning health system” (LHS) concept has been defined in broad terms, which makes it challenging for health system leaders to determine exactly what is required to transform their organization into an LHS. This study provides a conceptual map of the LHS landscape by identifying the activities, principles, tools, and conditions that LHS researchers have associated with the concept. Through a multi‐step screening process, two researchers identified 79 publications from PubMed (published before January 2020) that contained information relevant to the question, “What work is required of a healthcare organization that is operating as an LHS?” Those publications were coded as to whether or not they referenced each of 94 LHS elements in the taxonomy developed by the study team. This taxonomy, named the Learning Health Systems Consolidated Framework (LHS‐CF), organizes the elements into five “bodies of work” (organizational learning, translation of evidence into practice, building knowledge, analyzing clinical data, and engaging stakeholders) and four “enabling conditions” (workforce skilled for LHS work, data systems and informatics technology in place, organization invests resources in LHS work, and supportive organizational culture). We report the frequency that each of the 94 elements was referenced across the 79 publications. The four most referenced elements were: “organization builds knowledge or evidence,” “quality improvement practices are standard practice,” “patients and family members are actively engaged,” and “organizational culture emphasizes and supports learning.” By dissecting the LHS construct into its component elements, the LHS‐CF taxonomy can serve as a useful tool for LHS researchers and practitioners in defining the aspects of LHS they are addressing. By assessing how often each element is referenced in the literature, the study provides guidance to health system leaders as to how their organization needs to evolve in order to become an LHS ‐ while also recognizing that each organization should emphasize elements that are most aligned with their mission and goals.

Abstract Objective To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80–150 mg/kg/day). Methods Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). Results Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient

Abstract Background Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions. Methods We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003–2008. We included 26 population‐based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department. Results MPM patients mostly received chemotherapy alone (41%) or no cancer‐directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer‐directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department. Conclusions There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services. Key points Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer‐directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions. What this study adds: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.

Abstract We identify a disciplinary divide in how the environmental impacts of urbanization are presented in ecology and urban planning journals. We analyzed the sentiments expressed in 202,900 journal articles and found that articles in ecology journals discuss urbanization three times more negatively relative to urban planning journals. Articles in both disciplines identified the negative local impacts of urban growth on biodiversity, habitat, and other ecological outcomes. However, urban planning research also considered the positive global‐scale benefits of cities in enabling more efficient settlement patterns that reduce greenhouse gas emissions and energy consumption. These diverging perspectives are likely due to the different scales and scopes of the two disciplines, but also because of different counterfactuals: the alternative to urbanization might be car‐dependent exurbs, or simply no new development within the focal study area. Interdisciplinary collaborations may provide a path to reconcile the different perspectives and boost sustainability.

Abstract Background Impulsivity is a core feature of attention‐deficit/hyperactivity disorder (ADHD). Previous work using the delay discounting task to assess impulsivity reveals that adolescents with ADHD tend to prefer a smaller‐immediate reward over a larger‐delayed reward, and this relates to problematic choices in daily life. To gain a better understanding of daily decision‐making in adolescence, it is important to examine the social context, as peers have a major influence on decisions. Peer influence often has a negative connotation, but also provides an opportunity to promote positive outcomes. To date, it is unclear if peers affect impulsive decision‐making in adolescents with ADHD, for better or for worse. Methods The aim of this preregistered study was to examine the effect of peer feedback on impulsive choice in male adolescents with and without ADHD (ages 13–23; N = 113). We utilized an adapted delay discounting task that was administered alone, in a social condition, and alone again. In the social condition, adolescents received either (between‐subjects) manipulated impulsive or non‐impulsive peer feedback. Impulsive peer feedback consisted of likes for choosing the smaller immediate reward, whereas non‐impulsive peers endorsed choosing the larger delayed reward. Results Preregistered analyses showed that non‐impulsive peer feedback resulted in decreased impulsive choice, whereas impulsive peer feedback did not alter decision‐making in adolescents with and without ADHD. Explorative analyses of inattention and hyperactivity‐impulsivity symptoms in the total sample, irrespective of diagnosis, showed that lower hyperactivity–impulsivity and more inattention symptoms were associated with increased susceptibility to non‐impulsive peer feedback. Conclusions Together, these findings indicate that peers may provide an opportunity to decrease impulsivity and emphasize individual differences in susceptibility to non‐impulsive peer feedback related to inattention and hyperactivity–impulsivity. Therefore, peer feedback may be a promising component in behavioral peer‐supported interventions in adolescents with ADHD.

Abstract Background Adolescents with conduct problems (CP) are characterised by difficulties with social relationships and display atypical social cognition, such as when interpreting emotional expressions or engaging in social problem‐solving. One important aspect of social cognition that warrants investigation is the degree to which these adolescents factor others' views into their already held beliefs, and strategies used to do so. Effective social information use enables attunement to social environment, cooperation, and social problem‐solving. Difficulties in this regard could contribute to problems in social interactions in adolescents with CP, and may vary with adolescents' high (CP/HCU) versus low levels of callous‐unemotional traits (CP/LCU). Methods We compared social information use in boys (11–16 years) with CP/HCU (n = 32), CP/LCU (n = 31) and typically developing (TD) peers (n = 45), matched for IQ. Participants provided estimates of numbers of animals on a screen, saw another adolescent's estimate, and could adjust their initial estimate. We compared two aspects of social information use: (1) degree of adjustment of initial estimate towards another's estimate and (2) strategy use when adjusting estimates. Results Degree of adjustment towards another's estimate did not vary across groups, but strategy use did. Adolescents with CP/LCU compromised less following social information than TD peers. Conclusions Findings suggest that while adolescents with CP are able to take social information into account, those with CP/LCU use this information in a way that differs from other groups and could be less efficient. This warrants further systematic investigation as it could represent a target for behaviour management strategies. Overall, this study highlights the need for more research delineating the social‐cognitive profile of adolescents with CP/LCU.

Abstract Animals that rely extensively on scavenging rather than hunting must exploit resources that are inherently patchy, dangerous, or subject to competition. Though it may be expected that scavengers should therefore form opportunistic feeding habits in order to survive, a broad species diet may mask specialization occurring at an individual level. To test this, we used stable isotope analysis to analyze the degree of specialization in the diet of the Tasmanian devil, one of few mammalian species to develop adaptations for scavenging. We found that the majority of individuals were dietary specialists, indicating that they fed within a narrow trophic niche despite their varied diet as a species. Even in competitive populations, only small individuals could be classified as true trophic generalists; larger animals in those populations were trophic specialists. In populations with reduced levels of competition, all individuals were capable of being trophic specialists. Heavier individuals showed a greater degree of trophic specialization, suggesting either that mass is an important driver of diet choice or that trophic specialization is an efficient foraging strategy allowing greater mass gain. Devils may be unique among scavenging mammals in the extent to which they can specialize their diets, having been released from the competitive pressure of larger carnivores.

Abstract Background Foot disorders may limit independence and reduce quality of life for older adults. Obesity is a risk factor for foot conditions; both mechanical load and metabolic effects may contribute to these conditions. This study determined cross‐sectional associations between inflammatory markers and foot disorders. Methods Participants were drawn from the Framingham Foot Study (2002–2008). C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) were each examined for associations with foot pain, forefoot pain, hindfoot pain, hallux valgus, hallux rigidus, and toe deformities (claw, hammer, or overlapping toes). Unadjusted and adjusted (age, body mass index, physical activity, smoking status) sex‐specific logistic regression was performed. Results Of 909 participants, 54% were women (mean age 65 ± 9 years), 20% had foot pain, 29% had hallux valgus, 3% had hallux rigidus, and 27% had toe deformities. In unadjusted models, higher CRP (OR [95% CI] = 1.5 [1.1, 2.0]) and IL‐6 (OR [95% CI] = 1.8 [1.2, 2.6]) were associated with foot pain among men; higher CRP was associated with foot pain (OR [95% CI] = 1.3 [1.0, 1.5]) among women. Higher CRP (OR [95% CI] = 1.9 [1.1, 3.2]) and IL‐6 (OR [95% CI] = 2.4 [1.2, 4.7]) were associated with forefoot pain in men. Higher CRP was associated with hindfoot pain ([95% CI] = 1.8 [1.2, 2.6]) in women. After adjustment, CRP ([95% CI] = 1.5 [1.1, 2.0]) and IL‐6 ([95% CI] = 1.8 [1.2, 2.6]) remained associated with foot pain in men, and IL‐6 with forefoot pain ([95% CI] = 2.9 [1.4, 6.1]) in men. No associations with structural foot disorders were observed. Conclusions Inflammation may impact foot pain. Future work assessing whether inflammation is part of the mechanism linking obesity to foot pain may identify areas for intervention and prevention.

Abstract Introduction Resting cerebral blood flow (CBF) and perfusion measures have been used to determine brain health. Studies showing variation in resting CBF with age and fitness level using different imaging approaches have produced mixed findings. We assess the degree to which resting CBF measures through transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI provide complementary information in older and younger, fit and unfit cohorts. Methods Thirty‐five healthy volunteers (20 younger: 24 ± 7y; 15 older: 66 ± 7y) completed two experimental sessions (TCD/MRI). Aging and fitness effects within and between imaging modalities were assessed. Results Middle cerebral artery blood velocity (MCAv, TCD) was lower and transit time (MRI) slower in older compared with younger participants (p

Abstract Introduction An increasing number of studies are using magnetoencephalography (MEG) to study dementia. Here we define a common methodological framework for MEG resting‐state acquisition and analysis to facilitate the pooling of data from different sites. Methods Two groups of patients with mild cognitive impairment (MCI, n = 84) and healthy controls (n = 84) were combined from three sites, and site and group differences inspected in terms of power spectra and functional connectivity. Classification accuracy for MCI versus controls was compared across three different types of MEG analyses, and compared with classification based on structural MRI. Results The spectral analyses confirmed frequency‐specific differences in patients with MCI, both in power and connectivity patterns, with highest classification accuracy from connectivity. Critically, site acquisition differences did not dominate the results. Discussion This work provides detailed protocols and analyses that are sensitive to cognitive impairment, and that will enable standardized data sharing to facilitate large‐scale collaborative projects.

Abstract The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal), is a significant conservation threat to salamander biodiversity in Europe, although its potential to affect North American species is poorly understood. We tested the susceptibility of two genera (Eurycea and Pseudotriton) and three populations of lungless salamanders (Plethodontidae) to Bsal. All species became infected with Bsal and two (Pseudotriton ruber and Eurycea wilderae) developed chytridiomycosis. We also documented that susceptibility of E. wilderae differed among populations. Regardless of susceptibility, all species reduced feeding when exposed to Bsal at the highest zoospore dose, and P. ruber and one population of E. wilderae used cover objects less. Our results indicate that Bsal invasion in eastern North America could have significant negative impacts on endemic lungless salamander populations. Future conservation efforts should include surveillance for Bsal in the wild and in captivity, and championing legislation that requires and subsidizes pathogen‐free trade of amphibians.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with increased risk of cardiovascular events and mortality that can be attributed to accelerated atherosclerosis. This pilot study aimed to investigate if changes in blood parameters were compatible with atherosclerotic events in RA patients. To this aim, 45 RA women (aged more than 18 years), and 25 age and gender‐matched healthy donors (HD) were included. Biomarkers of oxidative stress, platelet activation and platelet aggregation were analysed in RA patients at baseline and after six months of treatment with disease modifying anti‐rheumatic drugs (DMARDs). Flow cytometry analysis revealed that ca. 4% of platelets was in activated state (evaluated in term of Annexin V and PAC‐1 positivity) in RA patients at baseline, and that the 76% of platelets displayed mitochondrial hyperpolarization. Moreover, platelets from RA patients at baseline aggregated more than those from HD after whole blood treatment with adenosine diphosphate. Interestingly, platelet aggregation in patients at baseline positively correlated with disease activity measured by DAS28 score. After six months of treatment with DMARDs, platelet activation and platelet aggregation reached values comparable to those of HD. Our preliminary data suggest that platelets might play an active role in the atherosclerosis occurring in RA patients.

Abstract Recent regional mountain pine beetle (MPB) outbreaks have generated unprecedented tree mortality across the fire‐prone landscapes of western North American forests and could potentially modify fire severity and postfire ecological effects. In 2012, 2013, and 2014, three fires burned through high mortality, gray‐phase lodgepole pine‐dominated forests in the plateau regions of central interior British Columbia, Canada, providing an opportunity to test for interactions between MPB outbreaks and wildfires. We inventoried 63 plots that spanned gradients of outbreak severity, fire severity, and burning conditions in a wilderness setting. Our objective was to evaluate the influence of outbreak severity on fire severity by assessing typical first‐order fire effects as well as legacy structure related to the consumption of woody biomass on snags/trees. We found no evidence of a relationship between outbreak severity and fire severity for six of seven first‐order fire effects, with the exception of deep charring. We found evidence that legacy structure in the form of consumed branch structure and deep char development had greater odds of occurrence on MPB‐killed snags compared to trees killed during wildfire. Our results indicate two key findings. First, fire severity as it relates to most first‐order fire effects measures is not influenced by outbreak severity, instead it is more strongly influenced by the interaction of fuels, weather, and topography during fire events. Second, our results highlight how the interaction between outbreak severity and fire severity alters postfire structural legacies and their functional attributes, which could have important ecosystem implications.

Background The American Heart Association Go Red for Women campaign has improved awareness of cardiovascular disease (CVD) among adult women aged 25 years and older. Little is known about awareness among younger women. Methods and Results We assessed awareness of CVD and prevention efforts among 331 young women aged 15 to 24 years using the American Heart Association National Women's Health Study survey. We compared responses from this cohort to the 2012 American Heart Association online survey of 1227 women aged 25 years and older. Only 33 (10.0%) young women correctly identified CVD as the leading cause of death in women. This was significantly lower than awareness among all adult women in 2012 (785 [64.0%]) and among women aged 25 to 34 years (90 of 168 [53.6%]) (P

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Background The state of the HIV epidemic in the Philippines has been described as “low and slow”, which is in stark contrast to many other countries in the region. A review of the conditions for HIV spread in the Philippines is necessary. Methods We evaluated the current epidemiology, trends in behaviour and public health response in the Philippines to identify factors that could account for the current HIV epidemic, as well as to review conditions that may be of concern for facilitating an emerging epidemic. Results The past control of HIV in the Philippines cannot be attributed to any single factor, nor is it necessarily a result of the actions of the Filipino government or other stakeholders. Likely reasons for the epidemic's slow development include: the country's geography is complicated; injecting drug use is relatively uncommon; a culture of sexual conservatism exists; sex workers tend to have few clients; anal sex is relatively uncommon; and circumcision rates are relatively high. In contrast, there are numerous factors suggesting that HIV is increasing and ready to emerge at high rates, including: the lowest documented rates of condom use in Asia; increasing casual sexual activity; returning overseas Filipino workers from high‐prevalence settings; widespread misconceptions about HIV/AIDS; and high needle‐sharing rates among injecting drug users. There was a three‐fold increase in the rate of HIV diagnoses in the Philippines between 2003 and 2008, and this has continued over the past year. HIV diagnoses rates have noticeably increased among men, particularly among bisexual and homosexual men (114% and 214% respective increases over 2003‐2008). The average age of diagnosis has also significantly decreased, from approximately 36 to 29 years. Conclusions Young adults, men who have sex with men, commercial sex workers, injecting drug users, overseas Filipino workers, and the sexual partners of people in these groups are particularly vulnerable to HIV infection. There is no guarantee that a large HIV epidemic will be avoided in the near future. Indeed, an expanding HIV epidemic is likely to be only a matter of time as the components for such an epidemic are already present in the Philippines.