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Abstract Background Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. Methods Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. Results Two hundred eighteen patients with stage I–III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2 mL/kg/min (IQR 10.6–14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8 mL/kg/min (IQR 15.4–23). On univariate linear regression analysis, male sex (P

Abstract Exsolution of metal nanoparticles (NPs) on perovskite oxides has been demonstrated as a reliable strategy for producing catalyst‐support systems. Conventional exsolution requires high temperatures for long periods of time, limiting the selection of support materials. Plasma direct exsolution is reported at room temperature and atmospheric pressure of Ni NPs from a model A‐site deficient perovskite oxide (La0.43Ca0.37Ni0.06Ti0.94O2.955). Plasma exsolution is carried out within minutes (up to 15 min) using a dielectric barrier discharge configuration both with He‐only gas as well as with He/H2 gas mixtures, yielding small NPs (

Abstract Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6‐guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT‐PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6‐impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6‐guided trial recommendations. The primary study outcome is the 3‐month absolute change in the composite pain intensity score assessed using Patient‐Reported Outcomes Measurement Information System (PROMIS) measures. Follow‐up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Abstract Burn severity is fundamental to post‐fire impact assessment and emergency response. Vegetation Burn Severity (VBS) can be derived from satellite observations. However, Soil Burn Severity (SBS) assessment—critical for mitigating hydrologic and geologic hazards—requires costly and laborious field recalibration of VBS maps. Here, we develop a physics‐informed Machine Learning model capable of accurately estimating SBS while revealing the intricate relationships between soil and vegetation burn severities. Our SBS classification model uses VBS, as well as climatological, meteorological, ecological, geological, and topographical wildfire covariates. This model demonstrated an overall accuracy of 89% for out‐of‐sample test data. The model exhibited scalability with additional data, and was able to extract universal functional relationships between vegetation and soil burn severities across the western US. VBS had the largest control on SBS, followed by weather (e.g., wind, fire danger, temperature), climate (e.g., annual precipitation), topography (e.g., elevation), and soil characteristics (e.g., soil organic carbon content). The relative control of processes on SBS changes across regions. Our model revealed nuanced relationships between VBS and SBS; for example, a similar VBS with lower wind speeds—that is, higher fire residence time—translates to a higher SBS. This transferrable model develops reliable and timely SBS maps using satellite and publicly accessible data, providing science‐based insights for managers and diverse stakeholders.

Abstract INTRODUCTION We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]). METHODS We used PallorMetrics to quantify optic disc pallor from fundus photographs, and pRNFL thickness from optical coherence tomography scans. Linear and logistic regression assessed relationships between retinal measures and SVD markers. Participants (N = 108, mean age 51.6) were from the PREVENT Dementia study. RESULTS Global optic disc pallor was linked to ePVSs in the basal ganglia in both left (β = 0.12, standard error [SE] = 0.05, P

Abstract Better understanding how fires respond to climate variability is an issue of current interest in light of ongoing climate change. However, evaluating the global‐scale temporal variability of fires in response to climate presents a challenge due to the intricate processes at play and the limitation of fire data. Here, we investigate the links between year‐to‐year variability of burned area (BA) and climate using BA data, the Fire Weather Index (FWI), and the Standardized Precipitation Evapotranspiration Index (SPEI) from 2001 to 2021 at ecoregion scales. Our results reveal complex spatial patterns in the dependence of BA variability on antecedent and concurrent weather conditions, highlighting where BA is mostly influenced by either FWI or SPEI and where the combined effect of both indicators must be considered. Our findings indicate that same‐season weather conditions have a more pronounced relationship with BA across various ecoregions, particularly in climatologically wetter areas. Additionally, we note that BA is also significantly associated with periods of antecedent wetness and coolness, with this association being especially evident in more arid ecoregions. About 60% of the interannual variations in BA can be explained by climatic variability in a large fraction (∼77%) of the world's burnable regions.

Abstract New results that employ Zr‐in‐rutile thermometry (ZiR) and quartz‐inclusion‐in‐garnet (QuiG) barometry constrain the P–T conditions of garnet formation in blueschists and eclogites from the island of Syros, Greece. QuiG barometry reveals that garnet from different regions across the island formed at pressures ranging from 1.1 to 1.8 GPa and ZiR thermometry on rutile inclusions in garnet constrains the minimum temperature of garnet formation to have been 475–550°C. Most importantly, there is no systematic difference in the conditions of garnet formation from different regions across the island and these results are nearly identical to those obtained from the islands of Sifnos and Ios, Greece. A model is proposed whereby the rocks from all three islands were initially metamorphosed along a relatively shallow geotherm of around 11°C/km to a depth of around 45 km and were then subjected to metamorphism along a geotherm of around 7–8°C/km, which could have been caused by either an increase in the dip of the subduction zone or an increase in the rate of subduction. Garnet formed along this steeper geotherm was accompanied by the release of significant H2O from the breakdown of chlorite over a duration of 1 Ma or less based on thermal and diffusion modeling. It is concluded that rocks from Syros, Sifnos and Ios all followed a similar, roughly counter‐clockwise prograde P–T path and that the present outcrop configuration is largely due to a complex exhumation history.

Branched chain amino acids (BCAAs) are essential for protein homeostasis, energy balance, and signaling pathways. Changes in BCAA homeostasis have emerged as pivotal contributors in the pathophysiology of several cardiometabolic diseases, including type 2 diabetes, obesity, hypertension, atherosclerotic cardiovascular disease, and heart failure. In this review, we provide a detailed overview of BCAA metabolism, focus on molecular mechanisms linking disrupted BCAA homeostasis with cardiometabolic disease, summarize the evidence from observational and interventional studies investigating associations between circulating BCAAs and cardiometabolic disease, and offer valuable insights into the potential for BCAA manipulation as a novel therapeutic strategy for cardiometabolic disease.

Abstract Automated computed tomography (CT) scan segmentation (labelling of pixels according to tissue type) is now possible. This technique is being adapted to achieve three‐dimensional (3D) segmentation of CT scans, opposed to single L3‐slice alone. This systematic review evaluates feasibility and accuracy of automated segmentation of 3D CT scans for volumetric body composition (BC) analysis, as well as current limitations and pitfalls clinicians and researchers should be aware of. OVID Medline, Embase and grey literature databases up to October 2021 were searched. Original studies investigating automated skeletal muscle, visceral and subcutaneous AT segmentation from CT were included. Seven of the 92 studies met inclusion criteria. Variation existed in expertise and numbers of humans performing ground‐truth segmentations used to train algorithms. There was heterogeneity in patient characteristics, pathology and CT phases that segmentation algorithms were developed upon. Reporting of anatomical CT coverage varied, with confusing terminology. Six studies covered volumetric regional slabs rather than the whole body. One study stated the use of whole‐body CT, but it was not clear whether this truly meant head‐to‐fingertip‐to‐toe. Two studies used conventional computer algorithms. The latter five used deep learning (DL), an artificial intelligence technique where algorithms are similarly organized to brain neuronal pathways. Six of seven reported excellent segmentation performance (Dice similarity coefficients > 0.9 per tissue). Internal testing on unseen scans was performed for only four of seven algorithms, whilst only three were tested externally. Trained DL algorithms achieved full CT segmentation in 12 to 75 s versus 25 min for non‐DL techniques. DL enables opportunistic, rapid and automated volumetric BC analysis of CT performed for clinical indications. However, most CT scans do not cover head‐to‐fingertip‐to‐toe; further research must validate using common CT regions to estimate true whole‐body BC, with direct comparison to single lumbar slice. Due to successes of DL, we expect progressive numbers of algorithms to materialize in addition to the seven discussed in this paper. Researchers and clinicians in the field of BC must therefore be aware of pitfalls. High Dice similarity coefficients do not inform the degree to which BC tissues may be under‐ or overestimated and nor does it inform on algorithm precision. Consensus is needed to define accuracy and precision standards for ground‐truth labelling. Creation of a large international, multicentre common CT dataset with BC ground‐truth labels from multiple experts could be a robust solution.

Abstract Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty‐five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p

Abstract Snow avalanches are thought to influence large wood dynamics within mountain streams, but studies that explicitly quantify their impact are minimal. In three headwater catchments of the Frying Pan River, Colorado, USA, we found that wood loads in stream reaches intersected by avalanche pathways ranged from 220 to 8,500 m3/ha and were significantly greater than in non‐avalanched reaches. Inter‐catchment differences in the number of avalanche occurrences were not reflected in control reach wood loads, suggesting that elevated loads may be restricted to the general vicinity of the avalanche pathway. However, the sizable wood volumes in avalanche reaches generated notable geomorphic impacts, indicating that avalanches can create hotspots of in‐stream geomorphic complexity and influence the overall habitat mosaic of the stream ecosystem. Loads in avalanche reaches were moreover significantly greater than literature values for similar streams and recruitment processes, emphasizing the importance of snow avalanches as a wood recruitment mechanism.

Abstract Extracellular vesicle (EV)‐carried miRNAs can influence gene expression and functional phenotypes in recipient cells. Argonaute 2 (Ago2) is a key miRNA‐binding protein that has been identified in EVs and could influence RNA silencing. However, Ago2 is in a non‐vesicular form in serum and can be an EV contaminant. In addition, RNA‐binding proteins (RBPs), including Ago2, and RNAs are often minor EV components whose sorting into EVs may be regulated by cell signaling state. To determine the conditions that influence detection of RBPs and RNAs in EVs, we evaluated the effect of growth factors, oncogene signaling, serum, and cell density on the vesicular and nonvesicular content of Ago2, other RBPs, and RNA in small EV (SEV) preparations. Media components affected both the intravesicular and extravesicular levels of RBPs and miRNAs in EVs, with serum contributing strongly to extravesicular miRNA contamination. Furthermore, isolation of EVs from hollow fiber bioreactors revealed complex preparations, with multiple EV‐containing peaks and a large amount of extravesicular Ago2/RBPs. Finally, KRAS mutation impacts the detection of intra‐ and extra‐vesicular Ago2. These data indicate that multiple cell culture conditions and cell states impact the presence of RBPs in EV preparations, some of which can be attributed to serum contamination.

Background High‐density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size‐based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size‐based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size‐based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi‐Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow‐up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size‐based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

Abstract Background Factors that influence prostate cancer treatment decisions are complex, multifaceted, and personal, and may vary by race/ethnicity. Although research has been published to quantify factors involved in decision‐making, these studies have been limited to primarily white, and to a lesser extent, Black patients, and quantitative studies are limited for discerning the cultural and contextual processes that shape decision‐making. Methods We conducted 43 semi‐structured interviews with a racially and ethnically diverse sample of patients diagnosed with low‐ and very‐low risk prostate cancer who had undergone treatment for their prostate cancer. Interviews were transcribed, independently coded, and analyzed to identify themes salient for decision‐making, with attention to sociocultural differences. Results We found racial and ethnic differences in three areas. First, we found differences in how socialized masculinity influenced patient's feelings about different treatment options. Second, we found that for some men, religion and spirituality alleviated anxiety associated with the active surveillance protocol. Finally, for racially and ethnically minoritized patients, we found descriptions of how historic and social experiences within the healthcare system influenced decision‐making. Conclusions Our study adds to the current literature by expounding on racial and ethnic differences in the multidimensional, nuanced factors related to decision‐making. Our findings suggest that factors associated with prostate cancer decision‐making can manifest differently across racial and ethnic groups, and provide some guidance for future research.

Objective Metabolic dysregulation frequently co‐occurs with obesity, which has been shown to be a risk factor for lower extremity osteoarthritis (OA). We evaluated the association between metabolic syndrome (MetS), alone and in combination with obesity, and hip OA. Methods In two parallel cross‐sectional analyses, we studied 403 women from the Study of Osteoporotic Fractures (SOF) and 2354 men from the Osteoporotic Fractures in Men (MrOS) study. We used multivariable logistic regression to evaluate associations of obesity (body mass index ≥30 kg/m2) and/or MetS (three of five National Cholesterol Education Program Adult Treatment Panel III criteria) with clinical hip OA, defined as a modified Croft score of 2 or more or total hip replacement, and pain or limited range of motion. Our analysis adjusted for demographics. Results Approximately 3.5% of SOF women and 5.4% of MrOS men had clinical hip OA. Among women, obesity was not associated with hip OA, yet those with MetS had a 365% higher odds of hip OA (95% CI: 1.37‐15.83). Among men, those who had obesity had a 115% higher odds of hip OA (95% CI: 1.39‐3.32), yet MetS was not associated with hip OA. There was no interaction between MetS, obesity, and hip OA in either women or men. Conclusion In women, but not in men, MetS was associated with hip OA. In men, but not in women, obesity was associated with hip OA. These findings suggest that mechanical effects of obesity may predominate in the pathogenesis of hip OA in men, whereas metabolic effects predominate in women.

Abstract Background The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health‐related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. Methods White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength

Abstract Measles, or rubeola, is a highly contagious acute febrile viral illness. Despite the availability of an effective vaccine since 1963, measles outbreaks continue worldwide. This article seeks to provide emergency physicians with the contemporary knowledge required to rapidly diagnose potential measles cases and bolster public health measures to reduce ongoing transmission.

Abstract Cloud‐to‐ground lightning with minimal rainfall (“dry” lightning) is a major wildfire ignition source in the western United States (WUS). Although dry lightning is commonly defined as occurring with

Abstract Background Accessibility to the immense collection of studies on noncommunicable diseases related to coronavirus disease of 2019 (COVID‐19) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an immediate focus of researchers. However, there is a scarcity of information about chronic obstructed pulmonary disease (COPD), which is associated with a high rate of infection in COVID‐19 patients. Moreover, by combining the effects of the SARS‐CoV‐2 on COPD patients, we may be able to overcome formidable obstacles factors, and diagnosis influencers. Materials and Methods A retrospective study of 280 patients was conducted at DHQ Hospital Muzaffargarh in Punjab, Pakistan. Negative binomial regression describes the risk of fixed successive variables. The association is described by the Cox proportional hazard model and the model coefficient is determined through log‐likelihood observation. Patients with COPD had their survival and mortality plotted on Kaplan–Meier curves. Results The increased risk of death in COPD patients was due to the effects of variables such as cough, lower respiratory tract infection (LRTI), tuberculosis (TB), and body‐aches being 1.369, 0.693, 0.170, and 0.217 times higher at (95% confidence interval [CI]: 0.747–1.992), (95% CI: 0.231–1.156), (95% CI: 0.008–0.332), and (95% CI: −0.07 to 0.440) while it decreased 0.396 in normal condition. Conclusion We found that the symptoms of COPD (cough, LRTI, TB, and bodyaches) are statistically significant in patients who were most infected by SARS‐CoV‐2.

Abstract The increasing complexity and impacts of fire seasons in the United States have prompted efforts to improve early warning systems for wildland fire management. Outlooks of potential fire activity at lead‐times of several weeks can help in wildland fire resource allocation as well as complement short‐term meteorological forecasts for ongoing fire events. Here, we describe an experimental system for developing downscaled ensemble‐based subseasonal forecasts for the contiguous US using NCEP's operational Climate Forecast System version 2 model. These forecasts are used to calculate forecasted fire danger indices from the United States (US) National Fire Danger Rating System in addition to forecasts of evaporative demand. We further illustrate the skill of subseasonal forecasts on weekly timescales using hindcasts from 2011 to 2021. Results show that while forecast skill degrades with time, statistically significant week 3 correlative skill was found for 76% and 30% of the contiguous US for Energy Release Component and evaporative demand, respectively. These results highlight the potential value of experimental subseasonal forecasts in complementing existing information streams in weekly‐to‐monthly fire business decision making for suppression‐based decisions and geographic reallocation of resources during the fire season, as well for proactive fire management actions outside of the core fire season.

Abstract Complex networks of relationships among and between people and nature (social‐ecological networks) play an important role in sustainability; yet, we have limited empirical understanding of their temporal dynamics. We empirically examine the evolution of a social‐ecological network in a common‐pool resource system faced with escalating social and environmental change over the past two decades. We first draw on quantitative and qualitative data collected between 2002 and 2018 in a Papua New Guinean reef fishing community to provide contextual evidence regarding the extent of social and environmental change being experienced. We then develop a temporal multilevel exponential random graph model using complete social‐ecological network data, collected in 2016 and 2018, to test key hypotheses regarding how fishing households have adapted their social ties in this context of change given their relationships with reef resources (i.e. social‐ecological ties). Specifically, we hypothesized that households will increasingly form tight‐knit, bonding social and social‐ecological network structures (H1 and H3, respectively) with similar others (H2), and that they will seek out resourceful actors with specialized knowledge that can promote learning and spur innovation (H4). Our results depict a community that is largely ‘bunkering down’ and looking inward in response to mounting risk to resource‐dependent livelihoods and a breakdown in the collaborative processes that traditionally sustained them. Community members are increasingly choosing to interact with others more like themselves (H2), with friends of friends (H1), and with those connected to interdependent ecological resources (H3)—in other words, they are showing a strong, increasing preference for forming bonding social‐ecological network structures and interacting with like‐minded, similar others. We did not find strong support for H4. Bonding network structures may decrease the risk associated with unmonitored behaviour and help to build trust, thereby increasing the probability of sustaining cooperation over time. Yet, increasing homophily and bonding ties can stifle innovation, reducing the ability to adapt to changing conditions. It can also lead to clustering, creating fault lines in the network, which can negatively impact the community's ability to mobilize and agree on/enforce social norms, which are key for managing common resources. Read the free Plain Language Summary for this article on the Journal blog.

Key Clinical Message A 64‐year‐old female presented with malaise and fever 11 days after a closed, minimally displaced humerus surgical neck fracture. MR imaging revealed an abscess around the fracture, which is a very rare occurrence in adults. Two open debridements and IV antibiotics eradicated the infection. Reverse total shoulder arthroplasty was eventually performed for fracture nonunion.

Abstract Coastal areas are some of the most densely populated and economically important regions in the world. As such, protecting the health of the human population and ecosystems at the coastal interface and understanding the impacts of environmental stressors such as air pollutants provides wide‐ranging benefits. Air quality (AQ) processes within coastal regions have been studied using ground and space‐based platforms, with intensive field campaigns focused on addressing key science questions that are typically partitioned into either direct atmospheric effects (e.g., anthropogenic emissions creating air pollution) or indirect processes and feedback loops (e.g., terrestrial/marine biogenic processes modifying atmospheric properties). The atmospheric planetary boundary layer (PBL) and its depth (or height) connect land, air, and the water surface via many pathways, especially with transport and exchange processes tied to the complexities of the coastal interface. We still cannot accurately characterize—through field, aircraft, or space‐based observations—the spatial and temporal PBL variability and processes within the PBL that couple together coastal dynamics and air quality. Several upcoming geostationary and polar‐orbiting satellite missions are likely to make significant progress in characterizing these air/land/water interactions over the next decade. Here, we present a framework of the current understanding of the PBL's role in coastal regions, primarily regarding air quality and atmospheric deposition, to motivate future concerted efforts from ground‐ and space‐based platforms to achieve a holistic understanding of the coastal interface.

Abstract Background Low back pain (LBP) is a heterogeneous disease with biological, physical, and psychosocial etiologies. Models for predicting LBP severity and chronicity have not made a clinical impact, perhaps due to difficulty deciphering multidimensional phenotypes. In this study, our objective was to develop a computational framework to comprehensively screen metrics related to LBP severity and chronicity and identify the most influential. Methods We identified individuals from the observational, longitudinal Osteoarthritis Initiative cohort (N = 4796) who reported LBP at enrollment (N = 215). OAI descriptor variables (N = 1190) were used to cluster individuals via unsupervised learning and uncover latent LBP phenotypes. We also developed a dimensionality reduction algorithm to visualize clusters/phenotypes using Uniform Manifold Approximation and Projection (UMAP). Next, to predict chronicity, we identified those with acute LBP (N = 40) and persistent LBP over 8 years of follow‐up (N = 66) and built logistic regression and supervised machine learning models. Results We identified three LBP phenotypes: a “high socioeconomic status, low pain severity group”, a “low socioeconomic status, high pain severity group”, and an intermediate group. Mental health and nutrition were also key clustering variables, while traditional biomedical factors (e.g., age, sex, BMI) were not. Those who developed chronic LBP were differentiated by higher pain interference and lower alcohol consumption (a correlate to poor physical fitness and lower soceioeconomic status). All models for predicting chronicity had satisfactory performance (accuracy 76%–78%). Conclusions We developed a computational pipeline capable of screening hundreds of variables and visualizing LBP cohorts. We found that socioeconomic status, mental health, nutrition, and pain interference were more influential in LBP than traditional biomedical descriptors like age, sex, and BMI.

Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Methods and Results Mice implanted with chronic cranial windows were trained for awake head‐fixation before experiments. One‐hour occlusion of the anterior middle cerebral artery branch was induced using single‐vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion‐fixed tissue by labeling lectin and platelet‐derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri‐ischemic cortex. Approximately half of the capillaries in the peri‐ischemic area were no longer perfused at the 3‐ and 24‐hour follow‐up (45% [95% CI, 33%–58%] and 53% [95% CI, 39%–66%] reduction, respectively; P

Abstract Introduction We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non‐demented older adults through its effects on medial temporal lobe (MTL) subregional volume. Methods Thirty‐two, non‐demented older adults with cerebrospinal fluid (CSF) (amyloid‐beta [Aβ]42/Aβ40, phosphorylated tau [p‐tau]181, total tau [t‐tau]), positron emission tomography (PET; 18F‐florbetapir), high‐resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI). Results Biomarkers of AD pathology were related to RI. Dentate gyrus (DG) and CA3 volume were uniquely associated with RI, whereas CA1 and BA35 volume were related to both RI and overall memory recall. AD pathology was associated with reduced BA35, CA1, and subiculum volume. DG volume and Aβ were independently associated with RI, whereas CA1 volume mediated the relationship between AD pathology and RI. Discussion Integrity of distinct hippocampal subfields demonstrate differential relationships with pathology and memory function, indicating specificity in vulnerability and contribution to different memory processes.

Background Cardiac failure is the primary cause of death in most patients with pulmonary arterial hypertension (PH). As pleiotropic cytokines, human resistin (Hresistin) and its rodent homolog, resistin‐like molecule α, are mechanistically critical to pulmonary vascular remodeling in PH. However, it is still unclear whether activation of these resistin‐like molecules can directly cause PH‐associated cardiac dysfunction and remodeling. Methods and Results In this study, we detected Hresistin protein in right ventricular (RV) tissue of patients with PH and elevated resistin‐like molecule expression in RV tissues of rodents with RV hypertrophy and failure. In a humanized mouse model, cardiac‐specific Hresistin overexpression was sufficient to cause cardiac dysfunction and remodeling. Dilated hearts exhibited reduced force development and decreased intracellular Ca2+ transients. In the RV tissues overexpressing Hresistin, the impaired contractility was associated with the suppression of protein kinase A and AMP‐activated protein kinase. Mechanistically, Hresistin activation triggered the inflammation mediated by signaling of the key damage‐associated molecular pattern molecule high‐mobility group box 1, and subsequently induced pro‐proliferative Ki67 in RV tissues of the transgenic mice. Intriguingly, an anti‐Hresistin human antibody that we generated protected the myocardium from hypertrophy and failure in the rodent PH models. Conclusions Our data indicate that Hresistin is expressed in heart tissues and plays a role in the development of RV dysfunction and maladaptive remodeling through its immunoregulatory activities. Targeting this signaling to modulate cardiac inflammation may offer a promising strategy to treat PH‐associated RV hypertrophy and failure in humans.

ABSTRACT The Mesoproterozoic Rossport Formation of Ontario, Canada is generally interpreted as having been deposited in an intracratonic basin, most probably a rift‐related lake. While the Rossport, overall, is dominated by sandstone and shale, the Middlebrun Bay Member, in the middle of the formation, is a carbonate unit. The Middlebrun Bay Member, in exposures on the Channel Islands and along the north Shore of Lake Superior, consists most commonly of cherty, dolomitic microbial laminites and low‐relief columnar to conical forms. In contrast to typical outcrops, the Middlebrun Bay Member on Copper Island expresses as a massive, coarsely crystalline limestone unit, devoid of stromatolites or microbial laminae. Several features suggest dissolution and replacement of a primary, soluble phase such as an evaporite mineral. The top of the unit is marked by evidence of dissolution and collapse, including large sandstone clasts let down from the overlying bed. At petrographic scale, the Copper Island Carbonate comprises millimetre‐scale anhedral spar with abundant stylolites and concentration of insoluble material at grain boundaries, indicating recrystallization from a previous phase. Geochemical data from Copper Island and from correlative stromatolitic carbonate on Channel Island and mainland Ontario are consistent with hypersaline conditions, with elevated concentrations of carbonate‐associated sulphate, V and Ba. Based on these data, the massive carbonate exposed on Copper Island is interpreted as a calcitized evaporite, probably deposited originally as gypsum, and replaced by calcite during diagenesis. These data support previous work suggesting that the Middlebrun Bay interval was deposited during a period of increased aridity and low clastic influx, and further suggest that this restricted, hypersaline lake precipitated both carbonate and gypsum, comparable to modern arid playa lakes.

Abstract Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance‐compliance time. In health, afterload stress stabilizes during steady‐state exercise. Our objective was to examine alterations of these exercise‐associated stresses in states of pre‐ and post‐capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady‐state exercise at moderate intensity in patients who exhibited Pre‐capillary (n = 22) and post‐capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR‐HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post‐capillary PH and NOR‐HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre‐capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance‐compliance time at rest (r2 = 0.843) and exercise (r2 = 0.760). Exercise resistance‐compliance time was longer in pre‐capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance‐compliance time was shortest in post‐capillary PH compared to pre‐capillary PH and NOR‐HD and associated with limited increases in exercise diastolic pressure gradient. During steady‐state, modest‐intensity exercise‐specific patterns of pulmonary vascular afterload responses were observed in pre‐ and post‐capillary PH relative to NOR‐HD. Longer resistance‐compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre‐capillary PH, while shorter resistance‐compliance time appeared to limit these increases in post‐capillary PH.

Abstract A respiratory disease epizootic at the National Bison Range (NBR) in Montana in 2016–2017 caused an 85% decline in the bighorn sheep population, documented by observations of its unmarked but individually identifiable members, the subjects of an ongoing long‐term study. The index case was likely one of a small group of young bighorn sheep on a short‐term exploratory foray in early summer of 2016. Disease subsequently spread through the population, with peak mortality in September and October and continuing signs of respiratory disease and sporadic mortality of all age classes through early July 2017. Body condition scores and clinical signs suggested that the disease affected ewe groups before rams, although by the end of the epizootic, ram mortality (90% of 71) exceeded ewe mortality (79% of 84). Microbiological sampling 10 years to 3 months prior to the epizootic had documented no evidence of infection or exposure to Mycoplasma ovipneumoniae at NBR, but during the epizootic, a single genetic strain of M. ovipneumoniae was detected in affected animals. Retrospective screening of domestic sheep flocks near the NBR identified the same genetic strain in one flock, presumptively the source of the epizootic infection. Evidence of fatal lamb pneumonia was observed during the first two lambing seasons following the epizootic but was absent during the third season following the death of the last identified M. ovipneumoniae carrier ewe. Monitoring of life‐history traits prior to the epizootic provided no evidence that environmentally and/or demographically induced nutritional or other stress contributed to the epizootic. Furthermore, the epizootic occurred despite proactive management actions undertaken to reduce risk of disease and increase resilience in this population. This closely observed bighorn sheep epizootic uniquely illustrates the natural history of the disease including the (presumptive) source of spillover, course, severity, and eventual pathogen clearance.

Abstract Background Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis. Methods and Results This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole‐body MB knockout resulted in impaired thermoregulation and cold‐ as well as drug‐induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential. Conclusions These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes.