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Nanotopographic surfaces are a powerful tool for studying and controlling cell behavior. However, the fabrication of nanotopographic master patterns using conventional photolithography is expensive, which limits the range of designs that can be explored. In this study, a method is demonstrated for the photoreshaping of large‐area patterns of nanoridges. The original master pattern is created using conventional lithography, and an azopolymer replica is prepared using soft lithography. The manipulation of the nanoridges is achieved by projecting light with specific polarizations and exposure times, resulting in controllable widening, buckling, or removal of the ridges. The reprogrammed azopolymer master patterns can then be replicated, creating reproducible new nanotopographies that can be transferred into other materials using a molding procedure. Diffraction can be used for in situ monitoring of the reprogramming during exposure. Image‐analysis methods are used to characterize buckled ridges as a function of exposure time. The response of MCF10A epithelial cells are investigated to buckled nanoridges. A substantial impact of buckling on the dynamics and location of actin polymerization, as well as on the distribution and lengths of contiguous polymerized regions is also observed. [ABSTRACT FROM AUTHOR]

Academic researchers faced a multitude of challenges posed by the COVID‐19 pandemic, including widespread shelter‐in‐place orders, workplace closures, and cessation of in‐person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web‐based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty. There were 116 musculoskeletal (MSK) researchers with varying demographic backgrounds who completed the survey. Of respondents, 48.3% (n = 56) believed that musculoskeletal funding opportunities decreased because of COVID‐19, with faculty members more likely to hold this belief compared to nonfaculty researchers (p = 0.008). Amongst MSK researchers, 88.8% (n = 103) reported research activity was limited by COVID‐19, and 92.2% (n = 107) of researchers reported their research was not able to be refocused on COVID‐19‐related topics, with basic science researchers less likely to be able to refocus their research compared to clinical researchers (p = 0.030). Additionally, 47.4% (n = 55) reported a decrease in manuscript submissions since the onset of the pandemic. Amongst 51 trainee researchers, 62.8% (n = 32) reported a decrease in job satisfaction directly attributable to the COVID‐19 pandemic. In summary, study findings indicated that MSK researchers struggled to overcome challenges imposed by the pandemic, reporting declines in funding opportunities, research productivity, and manuscript submission. Trainee researchers experienced significant disruptions to critical research activities and worsening job satisfaction. Our findings motivate future efforts to support trainees in developing their careers and target the recovery of MSK research from the pandemic stall. [ABSTRACT FROM AUTHOR]

Background: Magnetic hyperthermia (MHT) has emerged as a promising therapeutic approach in the field of radiation oncology due to its superior precision in controlling temperature and managing the heating area compared to conventional hyperthermia. Recent studies have proposed solutions to address clinical safety concerns associated with MHT, which arise from the use of highly concentrated magnetic nanoparticles and the strong magnetic field needed to induce hyperthermic effects. Despite these efforts, challenges remain in quantifying therapeutic outcomes and developing treatment plan systems for combining MHT with radiation therapy (RT). Purpose: This study aims to quantitatively measure the therapeutic effect, including radiation dose enhancement (RDE) in the magnetic hyperthermia‐radiation combined therapy (MHRT), using the equivalent radiation dose (EQD) estimation method. Methods: To conduct EQD estimation for MHRT, we compared the therapeutic effects between the conventional hyperthermia‐radiation combined therapy (HTRT) and MHRT in human prostate cancer cell lines, PC3 and LNCaP. We adopted a clonogenic assay to validate RDE and the radiosensitizing effect induced by MHT. The data on survival fractions were analyzed using both the linear‐quadradic model and Arrhenius model to estimate the biological parameters describing RDE and radiosensitizing effect of MHRT for both cell lines through maximum likelihood estimation. Based on these parameters, a new survival fraction model was suggested for EQD estimation of MHRT. Results: The newly designed model describing the MHRT effect, effectively captures the variations in thermal and radiation dose for both cell lines (R2 > 0.95), and its suitability was confirmed through the normality test of residuals. This model appropriately describes the survival fractions up to 10 Gy for PC3 cells and 8 Gy for LNCaP cells under RT‐only conditions. Furthermore, using the newly defined parameter r, the RDE effect was calculated as 29% in PC3 cells and 23% in LNCaP cells. EQDMHRT calculated through this model was 9.47 Gy for PC3 and 4.71 Gy for LNCaP when given 2 Gy and MHT for 30 min. Compared to EQDHTRT, EQDMHRT showed a 26% increase for PC3 and a 20% increase for LNCaP. Conclusions: The proposed model effectively describes the changes of the survival fraction induced by MHRT in both cell lines and adequately represents actual data values through residual analysis. Newly suggested parameter r for RDE effect shows potential for quantitative comparisons between HTRT and MHRT, and optimizing therapeutic outcomes in MHRT for prostate cancer. [ABSTRACT FROM AUTHOR]

In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university‐affiliated practice sites across Indiana. The overarching goal of this PGx implementation program was to facilitate the sustainable adoption of genotype‐guided prescribing into routine clinical care. To accomplish this goal, we pursued the following specific objectives: (i) to integrate PGx testing into existing healthcare system processes; (ii) to implement drug–gene pairs with high‐level evidence and educate providers and pharmacists on established clinical management recommendations; (iii) to engage key stakeholders, including patients to optimize the return of results for PGx testing; (iv) to reduce health disparities through the targeted inclusion of underrepresented populations; (v) and to track third‐party reimbursement. This tutorial details our multifaceted PGx implementation program, including descriptions of our interventions, the critical challenges faced, and the major program successes. By describing our experience, we aim to assist other clinical teams in achieving sustainable PGx implementation in their health systems. [ABSTRACT FROM AUTHOR]

SUMMARY Cultivar Williams 82 has served as the reference genome for the soybean research community since 2008, but is known to have areas of genomic heterogeneity among different sub‐lines. This work provides an updated assembly (version Wm82.a6) derived from a specific sub‐line known as Wm82‐ISU‐01 (seeds available under USDA accession PI 704477). The genome was assembled using Pacific BioSciences HiFi reads and integrated into chromosomes using HiC. The 20 soybean chromosomes assembled into a genome of 1.01Gb, consisting of 36 contigs. The genome annotation identified 48 387 gene models, named in accordance with previous assembly versions Wm82.a2 and Wm82.a4. Comparisons of Wm82.a6 with other near‐gapless assemblies of Williams 82 reveal large regions of genomic heterogeneity, including regions of differential introgression from the cultivar Kingwa within approximately 30 Mb and 25 Mb segments on chromosomes 03 and 07, respectively. Additionally, our analysis revealed a previously unknown large (>20 Mb) heterogeneous region in the pericentromeric region of chromosome 12, where Wm82.a6 matches the ‘Williams’ haplotype while the other two near‐gapless assemblies do not match the haplotype of either parent of Williams 82. In addition to the Wm82.a6 assembly, we also assembled the genome of ‘Fiskeby III,’ a rich resource for abiotic stress resistance genes. A genome comparison of Wm82.a6 with Fiskeby III revealed the nucleotide and structural polymorphisms between the two genomes within a QTL region for iron deficiency chlorosis resistance. The Wm82.a6 and Fiskeby III genomes described here will enhance comparative and functional genomics capacities and applications in the soybean community. [ABSTRACT FROM AUTHOR]

In social psychology these days it is commonplace to read or hear that liberal‐leftists and conservative‐rightists are every bit as “moral”; prejudiced and intolerant; susceptible to misinformation, “fake news,” and conspiratorial thinking; lax about upholding democratic standards; and prone to terrorism and political violence. Upon careful inspection, however, I conclude that every one of these claims is false or misleading. Liberal‐leftists in the United States and elsewhere are demonstrably more committed than conservative‐rightists to humanistic‐egalitarian values, deliberative reasoning, and adherence to democratic norms. In Western societies, acts of authoritarian aggression, hate crimes, and political violence are overwhelmingly more likely to come from the right than the left. As a witness to Nazi atrocities, Kurt Lewin deeply understood the role of historical, economic, and political forces in human lives and the interdependence between democracy and social science. He rejected moral relativism and what I call “both‐sideology” and offered a sophisticated critique of anti‐democratic tendencies. There are perfectly understandable reasons why people—especially academics and journalists—would be tempted to draw parallels between the left and right, and indeed there are many similarities as well as dissimilarities between liberal‐leftists and conservative‐rightists. However, the uncritical adoption of both‐sideology threatens liberal democracy itself and, with it, the only social science worth having. What we—as citizens and social scientists—need now is a renewal and revitalization of Lewin's critical‐emancipatory legacy before it is too late. [ABSTRACT FROM AUTHOR]

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 (<30 nm diameter). To prove the practical utility of exsolved NPs, various experiments aimed at assessing their catalytic performance for methanation from synthesis gas, CO, and CH4 oxidation are carried out. Low‐temperature and atmospheric pressure plasma exsolution are successfully demonstrated and suggest that this approach could contribute to the practical deployment of exsolution‐based stable catalyst systems. [ABSTRACT FROM AUTHOR]

Aim: Substantial progress has been made to map biodiversity and its drivers across the planet at multiple scales, yet studies that quantify the evolutionary processes that underpin this biodiversity, and test their drivers at multiple scales, are comparatively rare. Studying most fish species, we quantify rates of body size evolution to test the role of fundamental salinity habitats in shaping rates of evolution at multiple scales. We also determine how four additional factors shape evolutionary rates. Location: Global. Time Period: Extant species. Major Taxa Studied: Actinopterygii. Methods: In up to 1710 comparisons studying over 27,000 species, we compare rates of body size evolution among five salinity habits using 13 metrics. The comparisons span a molecular tree, 100 supertrees, and 10 scales of observation to test for robust patterns and reveal how patterns change with scale. Then, three approaches assess the role of three non‐salinity factors on rates, and an alternative habitat scheme tests if lakes influence evolutionary rates. Results: Rates of size evolution rarely differ consistently between salinity habitats; rate patterns are highly clade‐ and scale dependent. One exception is freshwater‐brackish fishes, which possess among the highest size rates of any salinity, showing higher rates than euryhaline fishes in most groupings studied at most scales, and versus marine, freshwater and marine–brackish habitats at numerous scales. Additionally, species richness had the greatest potential to predict phenotypic rates, followed by branch duration, then absolute values of body size. Lacustrine environments were consistently associated with high rates of size evolution. Main Conclusions: We reveal the rate patterns that underpin global body size diversity for fishes, identifying factors that play a limited role in shaping rates of size evolution, such as salinity, and those such as species richness, age and lake environments that consistently shape evolutionary rates across half of vertebrate diversity. [ABSTRACT FROM AUTHOR]

Catchment‐scale sediment storage is conceptualized as increasing in magnitude downstream, although reach‐scale controls may override this trend. We use empirical data from a literature review and two numerical models to quantitatively estimate sediment storage across the Colorado River Basin, USA. We use assumed alluvial thickness with floodplains delineated in the GFPLAIN model from 30 m digital elevation models. We use the SWAT+ model based on model‐estimated (i) groundwater storage and (ii) sediment storage. Existing studies indicate that sediment stored in floodplains and on low terraces is ~0.3–6 m thick. A first‐order approximation of volumetric storage capacity for natural floodplains is ~105 m3 per km. Sediment storage volumes of floodplains are ~108–1011 m3 over river lengths of 101–103 m. For the modeling estimates, we evaluated sediment storage by stream order and by elevation band within the Upper and Lower Colorado River Basins. Comparisons among the outputs cause us to place more confidence in the GFPLAIN and SWAT+ aquifer volume estimates. Each method includes substantial uncertainty and constitutes a first‐order approximation. Results suggest using 21 and 130 billion cubic meters as approximate lower and upper bounds for total sediment storage in the Upper Basin and 314 and 482 billion cubic meters as approximate lower and upper bounds for the Lower Basin. The largest proportion of sediment is stored in the montane and steppe zones in the Upper Basin and in the Sonoran zone in the Lower Basin. [ABSTRACT FROM AUTHOR]

An exponential rise in the atmospheric vapour pressure deficit (VPD) is among the most consequential impacts of climate change in terrestrial ecosystems. Rising VPD has negative and cascading effects on nearly all aspects of plant function including photosynthesis, water status, growth and survival. These responses are exacerbated by land–atmosphere interactions that couple VPD to soil water and govern the evolution of drought, affecting a range of ecosystem services including carbon uptake, biodiversity, the provisioning of water resources and crop yields. However, despite the global nature of this phenomenon, research on how to incorporate these impacts into resilient management regimes is largely in its infancy, due in part to the entanglement of VPD trends with those of other co‐evolving climate drivers. Here, we review the mechanistic bases of VPD impacts at a range of spatial scales, paying particular attention to the independent and interactive influence of VPD in the context of other environmental changes. We then evaluate the consequences of these impacts within key management contexts, including water resources, croplands, wildfire risk mitigation and management of natural grasslands and forests. We conclude with recommendations describing how management regimes could be altered to mitigate the otherwise highly deleterious consequences of rising VPD. Summary statement: Rising atmospheric vapour pressure deficit (or VPD) is one of the most widespread and significant consequences of climate warming for terrestrial ecosystems. This article reviews the mechanistic bases of these usually deleterious impacts and synthesises that information into a set of management recommendations to mitigate them. [ABSTRACT FROM AUTHOR]

Background: Young adults with elevated LDL‐C may experience increased burden of additional cardiovascular disease (CVD) risk factors. It is unclear how much LDL‐C levels, a modifiable factor, correlate with non‐LDL‐C CVD risk factors among young adults or how strongly these CVD risk factors are associated with long‐term predicted CVD risk. We quantified clustering of non‐LDL‐C CVD risk factors by LDL‐C among young adults to assess the association between non‐LDL‐C and LDL‐C risk factors with predicted CVD risk in young adults. Methods: The current analysis is a cross‐sectional study of adults < 40 years with an LDL‐C< 190 mg/dL participating in the National Health and Nutrition Examination Survey (NHANES) between January 2015 and March 2020. We measured the prevalence of non‐LDL‐C risk factors by LDL‐C and association between LDL‐C and non‐LDL‐C risk factors with predicted risk of CVD by the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations. Results: Among 2108 young adults, the prevalence of LDL‐C ≥ 130 mg/dL was 15.5%. Compared with young adults with LDL‐C < 100 mg/dL, those with LDL‐C 100–< 130, 130–< 160, and 160–< 190 mg/dL had greater non‐LDL‐C risk factors. Both LDL‐C and non‐LDL‐C risk factors were independently associated with a 30‐year risk of CVD (OR 1.05, 95% CI 1.03–1.07 and OR 1.17, 95% CI 1.12–1.23, respectively). The association of LDL‐C and 30‐year risk did not vary by non‐LDL‐C risk factor burden (pinteraction = 0.43). Conclusion: Non‐LDL‐C risk factors cluster among increasing levels of LDL‐C in young adults. Greater guidance on how to manage cardiovascular risk factors in young adults is needed. [ABSTRACT FROM AUTHOR]

The enzyme CbA5H, a [FeFe]‐hydrogenase from Clostridium beijerinckii, has previously been shown to survive exposure to oxygen, making it a promising candidate for biotechnological applications. Thus far [NiFe]‐hydrogenases are typically considered for such applications, due to the superior O2‐tolerance and therefore simplified enzyme handling. However, methods for production of [FeFe]‐hydrogenases are generally more successful than for other classes of hydrogenases, therefore in this work we focus on demonstrating scalable CbA5H production, and report results with active enzyme prepared in bioreactors (up to 10 L) with >20‐fold improvement in purified enzyme yield. We then go on to confirm excellent H2/H+‐cycling activity of the air‐purified protein, highlighting that CbA5H can be prepared and isolated without the need for complex and expensive infrastructure. Next, we demonstrate good stability of the air‐purified CbA5H both in solution assays, and as a heterogenous catalyst system when immobilized on a carbon support. Finally, we successfully implement this enzyme within previously demonstrated biotechnologies for flavin and NADH recycling, highlighting its relevance in chemical synthesis, and we demonstrate production of an important API precursor, 3‐quinuclidinol at >0.4 g scale in standard benchtop hydrogenation infrastructure, with >100,000 CbA5H turnovers over 18 operational hours. [ABSTRACT FROM AUTHOR]

The evolution of animals and their gut symbionts is a complex phenomenon, obscured by lability and diversity. In social organisms, transmission of symbionts among relatives may yield systems with more stable associations. Here, we study the history of a social insect symbiosis involving cephalotine ants and their extracellular gut bacteria, which come predominantly from host‐specialized lineages. We perform multi‐locus phylogenetics for symbionts from nine bacterial orders, and map prior amplicon sequence data to lineage‐assigned symbiont genomes, studying distributions of rigorously defined symbionts across 20 host species. Based on monophyly and additional hypothesis testing, we estimate that these specialized gut bacteria belong to 18 distinct lineages, of which 15 have been successfully isolated and cultured. Several symbiont lineages showed evidence for domestication events that occurred later in cephalotine evolutionary history, and only one lineage was ubiquitously detected in all 20 host species and 48 colonies sampled with amplicon 16S rRNA sequencing. We found evidence for phylogenetically constrained distributions in four symbionts, suggesting historical or genetic impacts on community composition. Two lineages showed evidence for frequent intra‐lineage co‐infections, highlighting the potential for niche divergence after initial domestication. Nearly all symbionts showed evidence for occasional host switching, but four may, more often, co‐diversify with their hosts. Through our further assessment of symbiont localization and genomic functional profiles, we demonstrate distinct niches for symbionts with shared evolutionary histories, prompting further questions on the forces underlying the evolution of hosts and their gut microbiomes. [ABSTRACT FROM AUTHOR]

Aim: Surgery for complex colorectal cancer is elaborate: preoperative assessment, patient selection, radiological interpretation, operative strategy, operative technical skills, operative standardization, postoperative care and management of complications are all critical components. Given this complexity, training that encompasses all these crucial aspects to generate suitably edified surgeons is essential. To date, no curriculum exists to guide training in advanced and recurrent pelvic malignancy, particularly for complex colorectal cancer. Such a curriculum would potentially offer numerous advantages, not only for individual surgeons but also for research, governance, international collaboration and benchmarking. The aim of this study was to design and develop a framework for a curriculum for fellowship training in complex colorectal cancer that encompasses pelvic exenteration surgery. Method: Kern described a six‐step method for curriculum design that is now widely adopted in medical education. Our study utilizes steps 1–4 of Kern's method to develop a syllabus and assessment framework for curriculum development for fellowship training in complex colorectal cancer encompassing pelvic exenteration. A literature review was conducted to address step 1, followed by targeted needs assessment in step 2 by conducting focus groups with trainees, fellows and experts to identify learning needs and goals with objective setting for step 3. An expert consensus group then voted on these recommendations and developed educational strategy recommendations as step 4. For the purposes of brevity, 'pelvic exenteration' in the text is taken to also encompass extended and multivisceral resections that fall under the remit of complex [colorectal] cancer. Results: Step 1 of Kern's method identified a gap in the literature on curricula in complex cancer surgery. Step 2 identified key areas regarded as learning needs by trainees, including anatomy, hands‐on experience and case volume. Step 3 defined the goals and objectives of a fellowship curriculum, defined in six domains including theoretical knowledge, decision‐making, technical skills, postoperative management and continuing professional development. Finally, as a prelude to stages 5 and 6, a strategy for implementation and for feedback and assessment was agreed by an expert consensus meeting that defined case volume (a minimum of 20 pelvic exenteration operations within a fellowship period) and coverage of this syllabus with derived metrics. Conclusions: Our working group has developed a curriculum framework for advanced fellowship training in complex cancer in the UK. Validation is needed through implementation, and affirmation of its utility, both nationally and internationally, must be sought. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: Post‐fire impact assessment and hazard mitigation heavily relies on burn severity metrics. Vegetation burn severity (VBS)—most relevant for ecological impacts—can be remotely sensed, but soil burn severity (SBS)—most relevant for hydrological impacts—requires laborious field recalibration of VBS maps. Lack of near real‐time SBS information is currently a data gap. Climate change‐driven weather whiplash can narrow the time interval between large wildfires and the ensuing precipitation events, requiring tools for rapid and accurate assessment of SBS without the need for laborious field recalibration of satellite‐derived metrics. Here we developed a physic‐informed Machine Learning model that can accurately develop SBS maps using readily available data without the need for resource and time intensive field assessments of burn severity. Additionally, SBS maps are developed for only a small fraction (less than 0.1%) of all wildfires in the US. Our model can develop SBS maps for all satellite‐observed wildfires in the western US, and has the potential to accomplish this task globally with further training. Finally, our model exhibited scalability with additional data, and was able to extract universal functional relationships between vegetation and soil burn severities across the western US. Key Points: Soil burn severity (SBS) assessment is key for hydrological hazard mitigationVegetation burn severity (VBS) can be remotely sensed, SBS is measured in the fieldPhysics‐informed Machine Learning models to translate VBS to SBS are developed [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

This study investigated the effects of once‐a‐day (OAD) and twice‐a‐day (TAD) milking strategies on Cheddar cheese properties, within an Irish pasture‐based system. Cheese derived from OAD milk was more yellow, with significantly higher b* values and a significantly higher β‐carotene content. A significantly higher cheese yield also resulted from OAD milk. Compositional data were largely consistent with previously reported results, and no meaningful differences were found in texture, proteolysis, pH, volatile‐organic‐compounds and free‐fatty‐acid profile. Indications are that OAD milking does not negatively impact Cheddar quality, providing valuable insights for those considering milking frequency impacts on this key dairy product. [ABSTRACT FROM AUTHOR]

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle‐aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non‐carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross‐sectional study, we investigated textural properties of T1‐weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT‐Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel‐based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non‐carriers. Textural maps were generated and were subsequently harmonised using voxel‐wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non‐carriers at midlife and have established associations of textural features with ageing and sex. [ABSTRACT FROM AUTHOR]

Aim: Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that lifestyle and/or behavioural interventions, such as participation in Special Olympics, decreases the risk of developing diabetes in adults with IDD could help minimize health disparities and promote overall health in this population. Methods: This was a 20‐year retrospective cohort study of adults with IDD (30–39 years) in the province of Ontario, Canada, that compared hazard rates of diabetes among Special Olympics participants (n = 4145) to non‐participants (n = 31,009) using administrative health databases housed at ICES. Using cox proportional hazard models, crude and adjusted hazard ratios were calculated for the association between the primary independent variable (Special Olympics participation status) and the dependent variable (incident diabetes cases). Results: After controlling for other variables, the hazard ratio comparing rates for developing diabetes between Special Olympics participants and non‐participants was 0.85. This represents a 15% reduction in the hazard among Special Olympics participants when followed for up to 20 years. This result was statistically significant and represents a small effect size. Conclusions: Special Olympics could be considered a complex intervention that promotes physical activity engagement through sport participation, health screenings, and the promotion of healthy eating habits through educational initiatives. This study provides evidence that Special Olympics participation decreases the rate for developing diabetes. [ABSTRACT FROM AUTHOR]

Summary: Plant survival to a potential plethora of diverse environmental insults is underpinned by coordinated communication amongst organs to help shape effective responses to these environmental challenges at the whole plant level. This interorgan communication is supported by a complex signal network that regulates growth, development and environmental responses. Nitric oxide (NO) has emerged as a key signalling molecule in plants. However, its potential role in interorgan communication has only recently started to come into view. Direct and indirect evidence has emerged supporting that NO and related species (S‐nitrosoglutathione, nitro‐linolenic acid) are mobile interorgan signals transmitting responses to stresses such as hypoxia and heat. Beyond their role as mobile signals, NO and related species are involved in mediating xylem development, thus contributing to efficient root–shoot communication. Moreover, NO and related species are regulators in intraorgan systemic defence responses aiming an effective, coordinated defence against pathogens. Beyond its in planta signalling role, NO and related species may act as ex planta signals coordinating external leaf‐to‐leaf, root‐to‐leaf but also plant‐to‐plant communication. Here, we discuss these exciting developments and emphasise how their manipulation may provide novel strategies for crop improvement. [ABSTRACT FROM AUTHOR]

Background Objectives Material and methods Results Discussion Conclusion Sex hormones are likely to be important determinants of COVID‐19 severity, and two opposing explanations regarding severity, the low‐androgen‐driven and high‐androgen‐driven theories, seek to explain this pattern. Digit ratios are sex dependent (males < females) and are claimed to be markers for both prenatal and postnatal testosterone.Here, we use a measure of COVID‐19severity (hospitalization), compare digit ratios in patients and controls and consider whether vaccination status changed these associations.Four digits were measured (2D, 3D, 4D, 5D). There were 194 participants (94 hospitalized patients [45 men] and 100 controls [53 men]) in Sample I and 162 participants (100 hospitalized [42 men], including 40 vaccinated and 62 controls [32 men]) in Sample II. Six ratios were calculated (2D:3D; 2D:4D; 2D:5D; 3D:4D; 3D:5D, 4D:5D) and compared between COVID‐19 hospitalized and non‐hospitalized patients and vaccinated and non‐vaccinated.In comparison to controls, we found higher (“feminized”) means in patient ratios that included 5D (2D:5D; 3D:5D; 4D:5D) in both samples. The differences were independent of sex and age. Hospitalized patients with COVID‐19 have higher (feminized) means and higher standard deviations (SDs) for 5D digit ratios.Digit ratios are sex dependent (males < females) and are considered as markers for both prenatal and postnatal testosterone. If verified in future studies, the results will be helpful in regard to targeting mortality‐reducing therapies for COVID‐19 in certain groups of patients.We conclude that the association between high (feminized) 5D ratios and hospitalization supports the low‐androgen‐driven theory of COVID‐19 severity. [ABSTRACT FROM AUTHOR]

Rangelands in the southwestern United States represent a current stronghold for northern bobwhite (Colinus virginianus); however, bobwhite populations in rangelands exhibit extreme inter‐annual variability in abundance in relation to fluctuating weather patterns. Recent declining bobwhite population trends within this region have led to the supposition that landscape‐scale processes, such as habitat loss and fragmentation and predation from increased raptor abundance, may be acting in conjunction with weather to reduce bobwhite populations. Our objective was to determine the relative effects of these factors on bobwhite populations in the rangeland environments of Texas and Oklahoma, USA. We obtained publicly available datasets for bobwhite counts (Breeding Bird Survey, state‐agency roadside counts), weather (PRISM), land cover (National Land Cover Database), and raptors (Christmas Bird Counts) for 3 5‐year periods (1990–1994, 1999–2003, 2009–2013). Data were collected at route and landscape scales based on routes within the Rio Grande Plains region of Texas and the Central Mixed Grass Prairie region of Texas and Oklahoma. We used generalized linear mixed models with a backward selection approach to determine top models for each dataset based on scale and ecoregion. Covariate relationships with bobwhite abundance followed expected patterns, with positive relationships with habitat, precipitation, and minimum temperatures and negative relationships with maximum temperatures and raptor abundance. Weather variables were the factors most consistently selected within both regions, while minimum winter temperature was overall the top variable. These relationships occurred within a landscape still containing relatively vast amounts of unfragmented bobwhite habitat (>60% rangeland; >15 million ha). Management within these regions should be focused on retaining habitat at a broad scale, while managing for suitable cover at a local scale to help mitigate weather effects. [ABSTRACT FROM AUTHOR]

The current study examined 98 participants' preferences for five pictorial stimuli. The researchers used a verbal multiple‐stimulus‐without‐replacement (VMSWO) preference assessment with each participant to identify high‐preference and low‐preference pictorial stimuli. Next, participants viewed each pictorial stimulus in a randomized order on a computer while using a hand dynamometer that measured the amount of force they exerted to increase or maintain the visual clarity of each image. The results indicate that over 75% of participants' force response ranks corresponded with participants' VMSWO high‐preference stimuli, VMSWO low‐preference stimuli, or both. The results of the current study provide further evidence for the use of conjugate schedules in the assessment of stimulus preference with potential for use as a reinforcer assessment. Implications along with directions for future research and limitations of the findings are discussed. [ABSTRACT FROM AUTHOR]

Inter‐annual precipitation in California is highly variable, and future projections indicate an increase in the intensity and frequency of hydroclimatic "whiplash." Understanding the implications of these shocks on California's water system and its degree of resiliency is critical from a planning perspective. Therefore, we quantify the resilience of reservoir services provided by water and hydropower systems in four basins in the western Sierra Nevada. Using downscaled runoff from 10 climate model outputs, we generated 200 synthetic hydrologic whiplash sequences of alternating dry and wet years to represent a wide range of extremes and transitional conditions used as inputs to a water system simulation model. Sequences were derived from upper (wet) and lower (dry) quintiles of future streamflow projections (2030–2060). Results show that carryover storage was negatively affected in all basins, particularly in those with lower storage capacity. All basins experienced negative impacts on hydropower generation, with losses ranging from 5% to nearly 90%. Reservoir sizes and inflexible operating rules are a particular challenge for flood control, as in extremely wet years spillage averaged nearly the annual basins' total discharge. The reliability of environmental flows and agricultural deliveries varied depending on the basin, intensity, and duration of whiplash sequences. Overall, wet years temporarily rebound negative drought effects, and greater storage capacity results in higher reliability and resiliency, and lesser volatility in services. We highlight potential policy changes to improve flexibility, increase resilience, and better equip managers to face challenges posed by whiplash while meeting human and environmental needs. Plain Language Summary: Inter‐annual precipitation is naturally highly variable in California, and future projections indicate an increase in the intensity and frequency of hydroclimatic "whiplash." This study investigates the potential impacts of these hydroclimatic events to comprehend their implications on California's water system and its level of resilience, which holds critical importance from a planning perspective. We focus on four basins in the western Sierra Nevada, to quantify the resilience of reservoir services provided by the water and hydropower systems in the region. Using downscaled runoff data from 10 climate models, we generated 200 synthetic hydrologic whiplash sequences to represent combinations of extreme wet and dry conditions. Results show that all basins experienced negative effects on carryover storage, with losses ranging from 5% to nearly 90%, consequently decreasing hydropower generation. Flood control is challenged during extremely wet years due to reservoir sizes and operating rules. The reliability of environmental flows and agricultural deliveries varied across basins and whiplash sequences. Wet years tend to mitigate negative drought effects temporarily, and greater storage capacity improved the reliability and resilience of services. We highlight the need for potential policy changes to enhance flexibility and resilience, and equip managers to face challenges posed by whiplash. Key Points: Wet years can temporarily rebound negative drought effects, although challenging flood control due to reservoir sizes and operating rules.Environmental flows and agricultural deliveries oscillated depending on the basin, intensity, and duration of whiplash sequences.Greater storage capacity generally provided greater reliability and resiliency, and lesser volatility in water and power services. [ABSTRACT FROM AUTHOR]

This study examined a conjugate approach for evaluating auditory stimulus preference for 81 participants using force as a continuous response dimension. First, the researchers used a verbal preference assessment to evaluate each participant's preference for listening to five genres of music. This process identified high‐preference and low‐preference music for each participant. Thereafter, the researchers exposed each participant to the five music genres in a randomized order while using a hand dynamometer to measure their response force to increase the auditory clarity of the music. The results indicate (a) 63% of the participants' high‐preference music genres corresponded to the genre for which they exerted the highest mean force and (b) most participants' low‐preference music genres corresponded to the genre for which they exerted the lowest mean force. These findings are consistent with those from Davis et al. (2021) and further support using conjugate preparations for measuring the relative value of some stimulus events. [ABSTRACT FROM AUTHOR]

Large wood is inherently mobile in naturally functioning river corridors, yet river management commonly introduces wood that is anchored to limit hazards. Wood that is periodically mobilized is important for: replacing stationary large wood that performs diverse physical and ecological functions; contributing to the disturbance regime of the river corridor; diversifying wood decay states; dispersing organisms and propagules; providing refugia during floodplain inundation and in mobile‐bed channels; dissipating flow energy; and supplying wood to downstream environments including lakes, coastlines, the open ocean, and the deep sea. We briefly review what is known about large wood mobility in river corridors and suggest priorities for ongoing research and river management, including: structural designs that can pass mobile wood; enhancing piece diversity of introduced wood that is anchored in place; quantifying wood mobilization and transport characteristics in natural and managed river corridors; and enhancing documentation of the benefits of wood mobility. [ABSTRACT FROM AUTHOR]

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 < 0.05) and right eyes (β = 0.13, SE = 0.05, P < 0.05). Associations were also noted in different disc sectors. No pRNFL associations with SVD markers were found. DISCUSSION: Optic disc pallor correlated with ePVSs in the basal ganglia, suggesting retinal examination may be a useful method to study brain health changes related to SVD. Highlights: Optic disc pallor is linked to enlarged perivascular spaces in basal ganglia.There is no association between peripapillary retinal nerve fiber layer thickness and cerebral small vessel disease markers.Optic disc examination could provide insights into brain health.The sample included 108 midlife adults from the PREVENT Dementia study. [ABSTRACT FROM AUTHOR]

Background/Objective: The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4‐repeat‐tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β‐amyloid status. Methods: Twenty‐five people with CBS, and 32 age‐/sex‐/education‐matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB‐J non‐displaceable binding potential (BPND), AD‐tau pathology by [18F]AV‐1451 BPND, and gray matter volume by T1‐weighted magnetic resonance imaging. Participants with CBS had β‐amyloid imaging with 11C‐labeled Pittsburgh Compound‐B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy‐rating‐scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. Results: Compared to controls, patients with CBS had higher [18F]AV‐1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β‐amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. Discussion: Distinct patterns of [11C]UCB‐J and [18F]AV‐1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: In the context of changing climatic conditions, it is increasingly important to better understand the relationship between climate and fires. This study proposes a method that evaluates climatic conditions, either antecedent to or coincident with the fire season or the composite effect of both. It shows that the interannual variability of the global burned area for the period 2001 to 2021 is explained by climatic factors by around 60%. Our results also indicate that climatic drivers concurrent to the fire season prevail moderately over the antecedents. This suggests that the expected increase in burned area due to warmer and/or drier conditions can be mitigated where these climate conditions limit fuel availability. Key Points: 2/3 of the interannual variations in area burned are explained by climate in a substantial portion of the world's burnable regionsSame‐fire‐season weather is moderately more important than antecedent‐fire‐season weather for burned area variabilityBurned area is associated with antecedent wet and cool periods especially in the more arid areas [ABSTRACT FROM AUTHOR]

Ecosystem state transitions can be ecologically devastating or be a restoration success. State transitions are common within aquatic systems worldwide, especially considering human‐mediated changes to land use and water use. We created a transferable conceptual framework to enable multiscale assessments of state resilience and early warnings of state transitions that can inform strategic restorations and avoid ecosystem collapse. The conceptual framework integrated machine learning predictions with ecosystem state concepts (e.g., state classification, gradients of vulnerability, and recovery potential leading to state transitions) and was devised to investigate possible environmental drivers. As an application of the framework, we generated prediction probabilities of submersed aquatic vegetation (SAV) presence at nearly 10,000 sites in the Upper Mississippi River (United States). Then, we used an interpretability method to explain model predictions to gain insights into possible environmental drivers and thresholds or linear responses of SAV presence and absence. Model accuracy was 89% without spatial bias. Average water depth, suspended solids, substrate, and distance to nearest SAV were the best predictors and likely environmental drivers of SAV habitat suitability. These environmental drivers exhibited nonlinear, threshold‐type responses for SAV. All the results are also presented in an online dashboard to explore results at many spatial scales. The habitat suitability model outputs and prediction explanations from many spatial scales (4 m to 400 km of river reach) can inform research and restoration planning. [ABSTRACT FROM AUTHOR]

Introduction: Digit ratio (2D:4D: the relative length of the 2nd and 4th digit) is thought to be a negative correlate of prenatal testosterone. The 2D:4D is related to oxygen metabolism, but the precise nature of this relationship is unclear. The purpose of the present study was to consider associations between digit ratios (right 2D:4D, left 2D:4D, right–left 2D:4D [Dr‐l]) and VO2max and ventilatory thresholds (VT1 and VT2). Methods: One hundred and thirty‐three Caucasian (n = 133) professional football players competing in Cyprus participated in the study. Players underwent anthropometric measurements, and digit lengths were measured from hand scans. They also completed an incremental cardiopulmonary test to exhaustion on a treadmill. Results: There were negative correlations between digit ratios and VO2max (right 2D:4D, r = −.65; left 2D:4D r = −.37, both p <.0001; Dr‐l r = −.30, p =.0005). There were no relationships between digit ratios and VT1. For VT2, there were negative relationships with digit ratios (right 2D:4D, r = −.43, p <.0001; left 2D:4D, r = −.21 and Dr‐l, r = −.21, both p =.02). Digit ratios are negatively related to VO2max with large (right 2D:4D) and medium (left 2D:4D, Dr‐l) effect sizes. For VT2, there were also negative correlations, which were medium (right 2D:4D) and small (left 2D:4D, Dr‐l). Conclusion: Our findings may help clarify the relationships between digit ratios and high‐intensity actions for extended periods, which are dependent on efficient oxygen metabolism. [ABSTRACT FROM AUTHOR]

Background and Objectives: When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time. Materials and Methods: Simulation methods are applied to create a cohort of donor recruits and patients over a 10‐year time horizon. New recruits are added to the registry each year, while some existing donors 'age‐out' upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry. Results: There are increased matches in non‐White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants. Conclusion: Preferentially recruiting from non‐Caucasian populations reduces the number of matches from Canadian sources because increases in non‐Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood‐brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD. METHODS: MINERVA was a single‐center, phase II, randomized, double‐blind, placebo‐controlled trial. Forty‐four participants with moderate‐to‐severe SVD took minocycline or placebo for 3 months. Co‐primary outcomes were microglial signal (determined using 11C‐PK11195 positron emission tomography) and BBB permeability (using dynamic contrast‐enhanced MRI). RESULTS: Forty‐four participants were recruited between September 2019 and June 2022. Minocycline had no effect on 11C‐PK11195 binding (relative risk [RR] 1.01, 95% confidence interval [CI] 0.98–1.04), or BBB permeability (RR 0.97, 95% CI 0.91–1.03). Serum inflammatory markers were not affected. DISCUSSION: 11C‐PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease‐causing remains unclear. INTERNATIONAL CLINICAL TRIALS REGISTRY PORTAL IDENTIFIER: ISRCTN15483452 Highlights: We found focal areas of increased microglial signal and increased blood‐brain barrier permeability in patients with small vessel disease.Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging.Blood‐brain barrier permeability was dynamic but MRI‐derived measurements correlated well with CSF/serum albumin ratio.Advanced neuroimaging is a feasible outcome measure for mechanistic clinical trials. [ABSTRACT FROM AUTHOR]

Vaspin is a serine protease inhibitor that protects against adipose tissue inflammation and insulin resistance, two key drivers of adipocyte dysfunction and metabolic disorders in obesity. Inhibition of target proteases such as KLK7 has been shown to reduce adipose tissue inflammation in obesity, while vaspin binding to cell surface GRP78 has been linked to reduced obesity‐induced ER stress and insulin resistance in the liver. However, the molecular mechanisms by which vaspin directly affects cellular processes in adipocytes remain unknown. Using fluorescently labeled vaspin, we found that vaspin is rapidly internalized by mouse and human adipocytes, but less efficiently by endothelial, kidney, liver, and neuronal cells. Internalization occurs by active, clathrin‐mediated endocytosis, which is dependent on vaspin binding to the LRP1 receptor, rather than GRP78 as previously thought. This was demonstrated by competition experiments and RNAi‐mediated knock‐down in adipocytes and by rescuing vaspin internalization in LRP1‐deficient Pea13 cells after transfection with a functional LRP1 minireceptor. Vaspin internalization is further increased in mature adipocytes after insulin‐stimulated translocation of LRP1. Although vaspin has nanomolar affinity for LRP1 clusters II‐IV, binding to cell surface heparan sulfates is required for efficient LRP1‐mediated internalization. Native, but not cleaved vaspin, and also vaspin polymers are efficiently endocytosed, and ultimately targeted for lysosomal degradation. Our study provides mechanistic insight into the uptake and degradation of vaspin in adipocytes, thereby broadening our understanding of its functional repertoire. We hypothesize the vaspin‐LRP1 axis to be an important mediator of vaspin effects not only in adipose tissue but also in other LRP1‐expressing cells. [ABSTRACT FROM AUTHOR]

Background: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors =8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. Methods: Eligible patients =30 years old with newly diagnosed EWS =8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. Results: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. Conclusion: This study demonstrates that definitive RT for pediatric and young adult patients with EWS =8 cm provides high rates of local control, while maintaining a tolerable toxicity profile. [ABSTRACT FROM AUTHOR]

Background: Most fractures occur in women aged ≥80 years but competing mortality unrelated to fracture may limit the benefit of osteoporosis drug therapy for some women in late life. Our primary aim was to develop separate prediction models for non‐spine fracture (NSF) and mortality before fracture to identify subsets of women with varying fracture versus mortality risks. Methods: Separate prediction models were developed for NSF and mortality before NSF for 4895 women aged ≥80 years enrolled in the Study of Osteoporotic Fractures (SOF) or the Health Aging and Body Composition (HABC) study. Proportional hazards models modified to account for competing mortality were used to identify candidate risk factors for each outcome. Predictors associated with NSF or mortality (p < 0.2) were included in separate competing risk models to estimate the cumulative incidence of NSF and mortality before NSF during 5 years of follow‐up. This process was repeated to develop separate prediction models for hip fracture and mortality before hip fracture. Results: Significant predictors of NSF (race, total hip BMD, grip strength, prior fracture, falls, and use of selective serotonin reuptake inhibitors, benzodiazepines, or oral/transdermal estrogen) differed from predictors of mortality before NSF (age, walking speed, multimorbidity, weight change, shrinking, smoking, self‐rated health, dementia, and use of warfarin). Within nine subsets of women defined by tertiles of risk, 5‐year outcomes varied from 28% NSF and 8% mortality in the high‐risk NSF/low‐risk mortality subset, to 9% NSF and 22% mortality in the low‐risk NSF/high‐risk mortality subset. Similar results were seen for predictors of hip fracture and mortality before hip fracture. Conclusion: Considerable variation in 5‐year competing mortality risk is present among women in late life with similar 5‐year NSF risk. Both fracture risk and life expectancy should inform shared clinical decision‐making regarding initiation or continuation of osteoporosis drug therapy for women aged ≥80 years. [ABSTRACT FROM AUTHOR]

Vertical profiles of nitric oxide (NO) concentration are derived between 120 and 250 km using updated NO emission rates measured by Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. The Naval Research Laboratory Mass Spectrometer Incoherent Scatter Radar (MSIS) 2.1 model is used to provide the required parameters of temperature, atomic oxygen number density, and molecule oxygen number density needed to derive the NO concentrations using a non‐local thermodynamic equilibrium (non‐LTE) model. The SABER NO concentration shows a significant correlation with solar activity with larger peak NO concentrations and higher altitude extent during solar maximum years compared to those during the solar minimum years. The SABER NO agrees well with the MSIS 2.1 NO at altitudes above 120 km for all latitudes, while the pronounced SABER‐MSIS NO discrepancy below 120 km is likely due to the temperature underestimation by MSIS 2.1. A detailed error analysis is presented and considers systematic and random errors in all the terms in the non‐LTE model used to derive the NO concentration. Random error in MSIS 2.1 temperature and atomic oxygen dominates the uncertainty in single NO profiles above 120 km. We estimated a systematic error up to ∼36% between 120 and 250 km during solar maximum years. Plain Language Summary: Nitric oxide (NO) is a minor constituent of the Earth's thermosphere and regulates the energy budget by emitting infrared radiation that cools the region. Understanding the distribution of the NO concentration is important in understanding the energy redistribution in the Earth's upper atmosphere. In this paper, a new NO concentration data set between 120 and 250 km from January 2002 to the present day is derived from the latest Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) NO emission measurements and Mass Spectrometer Incoherent Scatter Radar (MSIS) 2.1 empirical model of temperature and O, and O2 number density. The derived SABER NO concentration varies with solar activity. The SABER NO agrees well with the empirical MSIS 2.1 NO between 120 and 250 km. Below 120 km, the temperature may be warmer than predicted by MSIS 2.1, leading to a substantial difference between SABER NO and MSIS 2.1 NO. A comprehensive error analysis considering systematic and random errors in all the terms in the model used to derive the NO concentration from SABER data shows that the systematic uncertainty of the SABER NO density is up to 36% above 120 km. Key Points: The nitric oxide (NO) 5.3 μm infrared emission rates derived from Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) measurements have been updatedVertical profiles of NO concentration, spanning 20+ years, are derived from the SABER NO emission rates, and Mass Spectrometer Incoherent Scatter Radar (MSIS) 2.1 T, n(O), and n(O2)The SABER NO concentrations exhibit good agreement (±30%) with those in the MSIS 2.1 empirical model between 120 and 250 km [ABSTRACT FROM AUTHOR]

Background: Precision medicine, sometimes referred to as personalized medicine, is rapidly changing the possibilities for how people will engage health care in the near future. As technology to support precision medicine exponentially develops, there is an urgent need to proactively improve our understanding of precision medicine and pose important research questions (RQs) related to its inclusion in the education and training of future emergency physicians. Methods: A seven‐step process was employed to develop a research agenda exploring the intersection of precision and emergency medicine education/training. A literature search of articles about precision medicine was conducted first, which informed the creation of future four scenarios in which trainees and practicing physicians regularly discuss and incorporate precision medicine tools into their discussions and work. Based on these futurist narratives, potential education RQs were generated by an expert panel. A total of 59 initial questions were subsequently categorized and refined to a priority list through a nominal group voting method. The top/priority questions were presented at the 2023 SAEM Consensus Conference on Precision Medicine, Austin, Texas, for further input. Results: Eight high‐value education RQs were developed, reflecting a holistic view of the challenges and opportunities for precision medicine education in the knowledge, skills, and attitudes relevant to emergency medicine. These questions contend with topics such as most effective pedagogical methods; intended resulting outcomes and behaviors; the generational differences between practicing emergency physicians, educators, and future trainees; and the desires and expectations of patients. Conclusions: Emergency medicine and emergency physicians must be prepared to understand precision medicine and incorporate this information into their "toolbox" of thinking, problem solving, and communication with patients and colleagues. This research agenda on how best to educate future emergency physicians in the use of personalized data to provide optimal health care is the focus of this article. [ABSTRACT FROM AUTHOR]

Designing an electrocatalyst with low Pt content is an immediate need for essential reactions in low temperature fuel cell systems. In the present work, La0.9925Ba0.0075Al0.995Pt0.005O3 is aimed at using with low (only 0.5%) Pt doping as an electrocatalyst for oxygen reduction reaction (ORR). The low doping level renders exsolution of 1–2 nm nanoparticles with uniform dispersion upon reduction in H2/N2 at low temperatures. Pt exsolved perovskite oxides deliver significantly enhanced catalytic activity for ORR and improved stability in alkaline media. This study demonstrates that LaAlO3 with low noble metal content holds immense potential as an electrocatalyst in real fuel cell systems. [ABSTRACT FROM AUTHOR]

This special article describes the achievements and impact of Dr. Todd Siu‐Toa Ing, MBBS, (1933–2023) on the field of nephrology as recounted by a colleague from Hong Kong, a U.S. nephrologist ex‐trainee, and the daughter of an important mentor. Dr. Ing was a founding member of the International Society for Hemodialysis. He made important discoveries regarding the diagnosis of renal tubular acidosis and electrolyte transport in the gastrointestinal tract and published many innovative findings relating to peritoneal and hemodialysis. He was especially interested in nephrology and dialysis education and was co‐editor of a Handbook of Dialysis that has been in publication in five editions since 1988 with translation into many foreign languages. Dr. Ing was very supportive of nephrology in China as well as Chinese nephrologists practicing in the United States, and was a founding member of the Chinese American Society of Nephrology. [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: The metamorphism of rocks in subduction zones releases large quantities of H2O, which ultimately helps flux melting in the overlying mantle leading to explosive island arc volcanism and provides a trigger for large earthquakes. One of the dominant processes that produce large amounts of H2O is the formation of the mineral garnet. Here, we present results that constrain the pressure and temperature conditions for the formation of garnet from three islands in the Greek Cyclades: Syros, Sifnos, and Ios. Our results indicate that garnet formed in different rocks on all three islands in a similar subduction channel along a trajectory where the pressure increase was relatively rapid and the temperature remained nearly constant. The duration of garnet formation in the entire suite of samples is estimated to have occurred in 1 million years or less, during which time significant quantities of fluid are inferred to have been released and which most likely had a major impact on volcanism and seismicity in the region while subduction was active. Key Points: Blueschist and eclogite assemblages do not necessarily reflect equilibrium crystallizationExhumation following garnet growth must occur within 1 Ma to preserve compositional zoningThe prograde subduction P–T path in the Cyclades is concave upward with initial shallow subduction followed by near isothermal loading [ABSTRACT FROM AUTHOR]

In order to examine the progressive chemical evolution of halogens (F, Cl, Br, I) in altered ocean crust (AOC) during prograde subduction, this study compares bulk and in situ halogen concentrations in mafic samples from three petrogenetically related exhumed terrains in the Western Alps (the Chenaillet ophiolite, the Queyras ophiolites of the Schistes Lustrés, and the Monviso ophiolite). Samples from the Chenaillet ophiolite represent oceanic crust unaffected by metamorphic halogen loss and define a protolith halogen content (122 μg/g F, 29 μg/g Cl, 82 ng/g Br, and 98 ng/g I). Samples from the Queyras ophiolites experienced blueschist facies conditions, undergoing recrystallization and halogen loss (74 μg/g F, 19 μg/g Cl, 70 ng/g Br, and 63 ng/g I). Eclogite facies samples from the Monviso meta‐ophiolite exhibit markedly reduced Cl (8 μg/g Cl) and Br (42 ng/g Br) contents relative to samples from Chenaillet and Queyras. Using electron probe microanalysis (EPMA), F and Cl host minerals (e.g., amphibole, chlorite, epidote) are identified and characterized in selected samples, showing a broad distribution of F and Cl, lending support to the view that halogen devolatilization in the subducting slab occurs continuously and is not dependent on the breakdown of a particular phase. In situ Cl concentrations decrease significantly between sub‐greenschist and blueschist assemblages. Fluorine is retained within subducting AOC and is decoupled from the heavy halogens (Cl, Br, I), which undergo continuous devolatilization during prograde metamorphism. Plain Language Summary: Halogens are volatile elements found predominantly in the Earth's oceans and sediments. During hydrothermal processes, they bond with other elements to form volatile‐bearing minerals. Tectonic processes can bring halogen‐enriched rocks into subduction zones, regions where one tectonic plate submerges beneath another. Subduction governs the transport of material from Earth's surface to its interior, influencing the chemical evolution of the crust, atmosphere, hydrosphere, and mantle. As the subducting plate carries rocks to greater depths beneath the surface, volatile‐bearing minerals destabilize, releasing volatile components as fluids. Halogens alter the properties of subduction‐derived fluids and impact the behavior of other biologically, climatically, and economically important elements (e.g., H2O, CO2, Au). Due to the influential role of halogens in subduction zone environments, the timing and extent of halogen loss must be constrained. This study investigates metamorphic rock samples from the Western Alps which underwent halogen‐enrichment followed by subduction and devolatilization. Results show that halogens behave differently from each other. Fluorine is not removed; it is retained until deep in the subduction zone and is returned to the Earth's mantle. The efficient removal of the other halogens occurs early in subduction (<60 km depth) and is not linked to the destabilization of a specific mineral. Key Points: Exhumed ophiolites in the Western Alps record prograde subduction zone metamorphism and halogen devolatilization of altered ocean crustResults show halogen decoupling. Fluorine is retained, whereas heavy halogens are mobilized from mafic rocks in the subducting slabDevolatilization of altered ocean crust occurs early in subduction; a significant portion of Cl, Br, and I is lost prior to eclogite facies [ABSTRACT FROM AUTHOR]

The twisted‐winged parasite genus Stylops has a history of different species concepts with varying host specificity resulting in diverse species diversity estimates in different regions of the Holarctic. The adoption of a supergeneralist species concept in Europe, proposing synonymization of all Western Palaearctic Stylops species, did not facilitate taxonomic clarity and obscured the available life‐history data in the region for decades. Lack of molecular data has allowed divergent opinions on species hypotheses and little opportunity for evaluating them in this morphologically challenging genus. To solve these discrepancies and gain novel information about host associations, we applied whole‐genome sequencing to 163 specimens, representing a significant portion of putative European species. We evaluate the existing and conflicting species hypotheses with molecular species delimitation using Species bOundry Delimitation using Astral (SODA) and use a maximum likelihood phylogeny to investigate host associations of the species. Furthermore, we evaluate the effect of a number of loci used in SODA for the number of inferred species. We find justification for synonymization of multiple species and indications of undescribed species, as well as new host–parasite relationships. We show that the number of inferred species in SODA is exceedingly and positively correlated with the number of loci used, urging for cautious application. The results of our study bring clarity to the Western Palaearctic species diversity of Stylops. Furthermore, the comprehensive molecular dataset generated in this study will be a valuable resource for future studies on Stylops and the evolution of parasites in general. [ABSTRACT FROM AUTHOR]

Lack of ecological knowledge is a major challenge for effective conservation of threatened plant species in Australia as disturbance events, such as wildfire, increase in frequency and magnitude. Rapid on‐ground surveys are increasingly important to inform recovery strategies for rare and threatened plants in response to extreme wildfire events, yet resources are rarely available to deploy time‐sensitive surveys. Here, we utilize a rapid on‐ground survey and monitoring program to document basic biological and ecological information for 21 rare and threatened plant species from the New England bioregion in northern New South Wales, which were affected by the catastrophic 2019–2020 megafires. Our results fill an important knowledge gap of ecology, population size, distribution and response to fire for these taxa, document for the first time a species distribution pattern within the Torrington State Conservation Area and reveal previously undocumented plant–insect interactions for nine species, including likely pollination of Persoonia terminalis ssp. terminalis and Monotaxis macrophylla by native bee (Hymenoptera) and fly (Diptera) species. Our findings reveal that two species (Cassinia heleniae and Hakea macrorrhyncha) have scarce distribution and low population sizes, despite neither having a conservation listing and their threat status should be urgently assessed. Simple rapid on‐ground surveys can be more cost effective for delivering long‐term conservation outcomes for rare and threatened taxa and we advocate that future funding and prioritisation processes must support the immediate delivery of such surveys in response to disturbance events. [ABSTRACT FROM AUTHOR]

Purpose: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). Materials and Methods: A previously validated smart phone app (M‐app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M‐app notifications were sent 4‐times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined. Results: A total of 204 participants enrolled in the M‐app study (64% female). M‐app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability. Conclusions: PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses. [ABSTRACT FROM AUTHOR]