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Background: Standard Cartesian time‐of‐flight (TOF) head magnetic resonance angiography (MRA) is routinely used to evaluate the intracranial arteries, but does not provide quantitative hemodynamic information that is useful for patient risk stratification as well as for monitoring treatment and tracking changes in blood flow over time. Quantitative TOF (qTOF) MRA represents a new and efficient method for simultaneous evaluating the intracranial arteries and quantifying blood flow velocity, but it has not yet been evaluated in patients with cerebrovascular disease. Purpose: To evaluate qTOF for simultaneously evaluating the intracranial arteries and quantifying intracranial blood flow velocity in patients with cerebrovascular disease, without the need for a phase contrast (PC) scan. Study Type: Prospective. Subjects: Twenty‐four patients (18 female, 6 male) with cerebrovascular disease. Field Strength/Sequences: Head MRA at 3 T using gradient‐echo 3D qTOF, standard Cartesian TOF, and PC protocols. Assessment: Three independent readers assessed arterial image quality using a 4‐point scale (1: non‐diagnostic, 4: excellent) and artifact presence. Total and component flow velocities obtained with qTOF and PC were measured. Statistical Tests: Wilcoxon signed‐rank tests, Gwet's AC2, intraclass correlation coefficients (ICC) for absolute agreement, Bland–Altman analyses, tests of equal proportions. P values <0.05 were considered statistically significant. Results: Averaged across readers and compared to standard Cartesian TOF, qTOF significantly improved overall arterial image quality (3.8 ± 0.2 vs. 3.6 ± 0.5), image quality at locations of pathology (3.7 ± 0.5 vs. 3.4 ± 0.7), and increased the proportion of evaluations rated without artifacts (63.9% [46/72] vs. 37.5% [27/72]). qTOF significantly agreed with PC for total flow velocity (ICC = 0.71) and component flow velocity (ICC = 0.89). Data Conclusion: qTOF angiography of the head matched or improved upon the image quality of standard Cartesian TOF, reduced image artifacts, and provided quantitative hemodynamic data, without the need for a PC scan. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Summary: Grasses (Poaceae) comprise c. 11 800 species and are central to human livelihoods and terrestrial ecosystems. Knowing their relationships and evolutionary history is key to comparative research and crop breeding. Advances in genome‐scale sequencing allow for increased breadth and depth of phylogenomic analyses, making it possible to infer a new reference species tree of the family.We inferred a comprehensive species tree of grasses by combining new and published sequences for 331 nuclear genes from genome, transcriptome, target enrichment and shotgun data. Our 1153‐tip tree covers 79% of grass genera (including 21 genera sequenced for the first time) and all but two small tribes. We compared it to a newly inferred 910‐tip plastome tree.We recovered most of the tribes and subfamilies previously established, despite pervasive incongruence among nuclear gene trees. The early diversification of the PACMAD clade could represent a hard polytomy. Gene tree–species tree reconciliation suggests that reticulation events occurred repeatedly. Nuclear–plastome incongruence is rare, with very few cases of supported conflict.We provide a robust framework for the grass tree of life to support research on grass evolution, including modes of reticulation, and genetic diversity for sustainable agriculture. [ABSTRACT FROM AUTHOR]

Background: Adverse pathology (AP) is often used as an intermediate end point for long‐term outcomes in men with prostate cancer (PCa) who are active surveillance candidates. The association between a commonly used AP definition and long‐term outcomes was tested, which identified definitions more strongly linked to a high risk of metastasis. Methods: Data were reviewed from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing radical prostatectomy (RP) from 1988 to 2020 at nine Veterans Affairs hospitals. Men meeting National Comprehensive Cancer Network low‐risk and favorable intermediate‐risk criteria were included. Men with and without AP were compared; men with AP were defined as having grade groups 3–5 or pathological stage ≥pT3a or pN1 at RP (definition 1). Sensitivity analyses were performed for six alternative definitions (definitions 2–7) and their association with biochemical recurrence (BCR), metastasis, PCa‐specific mortality (PCSM), and castrate‐resistant PCa (CRPC). Results: A total of 2175 men were included: 711 had AP by definition 1. In univariable analyses, all AP definitions were associated with the risk of BCR, metastasis, and PCSM. All but one definition were associated with CRPC. In definitions 1–6, the 10‐year event rate for metastasis in those with AP ranged from 3.0% (definition 1) to 7.9% (definition 5). Only in definition 7 was the 10‐year event rate for metastasis >10%. However, only 0.5% of patients (11 of 2175) met definition 7. Conclusions: AP was statistically associated with relatively worse outcomes. However, in all but the most stringent definitions, met by <1% of patients, the absolute event rate of metastasis in men with AP was low. This challenges the clinical usefulness of AP as an intermediate end point in men with intermediate‐ to low‐risk PCa. Although different adverse pathology definitions predict a higher risk of biochemical recurrence, metastasis, castrate‐resistant prostate cancer, and prostate cancer–specific mortality, the absolute incidence of adverse outcomes is very low in patients who have low‐risk or favorable intermediate‐risk prostate cancer. Thus, adverse pathology is not likely to be a clinically useful intermediate end point. [ABSTRACT FROM AUTHOR]

Eclogite‐facies rocks provide important constraints on the behaviour of convergent plate boundaries and the geometries of tectonic reconstructions due to the high to ultrahigh pressure conditions at which they form. Many eclogite occurrences are documented near the suture zone of active collisional settings where they are interpreted to mark the approximate location of former ocean basin subduction. Such observations influence tectonic interpretations for older eclogites within more deeply eroded and/or less well‐exposed terranes. The eclogitic Glenelg inlier in northwest Scotland is one such example, with c. 1 Ga eclogites having previously been interpreted as marking the trace of a Grenville‐aged collisional suture zone that defines a third 'arm' to the Grenville orogen alongside well‐defined sutures in North America and Scandinavia. Here we use a combination of geochronology, phase equilibrium modelling and accessory‐phase thermometry to show that the eclogite‐facies assemblages were produced at ∼$$ \sim $$18–19 kbar and 700°C–750°C from c. 1.1 to 1.0 Ga. Accounting for the foreland basin setting of equivalent‐aged sedimentary rocks in the region and demonstrating the thermal viability of this setting, we show that eclogite formation occurred in deforming foreland crust adjacent to the Grenville orogen, in a setting broadly analogous to fault‐bounded basement uplifts in the forelands of active deformation belts, such as the Himalayas and Andes. Our results demonstrate that eclogite‐facies rocks can form in a greater range of tectonic settings than are sometimes considered, with implications for tectonic reconstructions of collisional zones. In this instance, our results remove the need for a third 'arm' of the Grenville orogen by placing Glenelg in a foreland setting, reconciling the absence of plentiful Grenville‐aged metamorphic rocks in northwest Scotland, the sedimentological record and paleomagnetic data in the wider region. [ABSTRACT FROM AUTHOR]

Professor Peter John Lea, a highly esteemed scientist and Emeritus Professor at Lancaster University, passed away in June 2024. He was renowned for his research on nitrogen assimilation in plants and his contributions to crop improvement. Throughout his career, he published over 300 papers, mentored students, and served as a Senior Editor for the Annals of Applied Biology. Colleagues and friends remember him fondly for his scientific achievements and personal kindness. [Extracted from the article]

Present day submarine canyons are active conduits for the transfer of large volumes of sediment, carbon and pollutants from continents to oceans. However, the evolution of submarine canyons over geological timescales remains poorly understood due to their erosional nature and low preservation potential. The Late Cretaceous Punta Baja Formation represents a well‐preserved submarine canyon‐fill that evolved on a tectonically‐active ocean‐facing margin. Exposures provide kilometre‐scale continuous strike and dip sections of the 120 m thick and 1.2 km wide feature. An inherited tectonic fabric influenced the location and orientation of canyon incision into fluvial bedrock. The stratigraphic evolution of the Punta Baja submarine canyon is reconstructed from incision to fill, which shows that it remained an active sediment conduit throughout the time represented by the preserved fill. The depositional architecture of the north–south oriented erosionally confined canyon‐fill is asymmetrical, with sub‐vertically stacked channel‐fills to the west, and an overbank confined by the canyon margin to the east. Sedimentary process interactions led to depositional patterns that are considered distinct to submarine canyon fills. Dynamic topography generated by mass‐wasting processes captured sediment and drove knickpoint development, an autogenic mechanism that modifies sediment delivery to the ocean floor. Widespread upstream dipping surfaces in channel‐fills are interpreted as the stratigraphic expression of upstream migrating supercritical‐flow bedforms, which played an important role in sediment storage and transport in the canyon. The steep relief and internal topography of canyons leads to complicated and characteristic confined overbank flow behaviour and depositional patterns. This study provides insight into how processes that are observed in modern canyons are selectively preserved through the lifetime of the canyon and construct or destroy stratigraphy on geological timescales. [ABSTRACT FROM AUTHOR]

Hydrogen isotope exchange (HIE) via C−H activation constitutes an efficient method for the synthesis of isotopically‐enriched compounds, which are crucial components of the drug discovery process and are extensively employed in mechanistic studies. A series of iridium(I) complexes, bearing a chelating phosphine‐N‐heterocyclic carbene ligand, was designed and synthesized for application in the catalytic HIE of challenging N‐ and O‐aryl carbamates. A broad range of substrates were labeled efficiently, and applicability to biologically‐relevant systems was demonstrated by labeling an ʟ‐tyrosine‐derived carbamate with excellent levels of deuterium incorporation. Combined theoretical and experimental studies unveiled intriguing mechanistic features within this process, in comparison to C−H activation and hydrogen isotope exchange catalyzed by monodentate Ir(I) NHC/phosphine complexes. [ABSTRACT FROM AUTHOR]

Objectives: To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour. Patients and Methods: Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate‐specific membrane antigen‐positron emission tomography/computed tomography (PSMA‐PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence‐free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre‐ and post‐surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA‐PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria. Results: Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3‐year BRFS for both pre‐ and post‐surgical models. SUVmax change from 4 to 16 lessened the predicted 3‐year BRFS from 66% to 42% for a patient aged 65 years with typical pre‐surgical parameters (PSA level 8 ng/mL, Prostate Imaging‐Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post‐surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3‐year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed. Conclusion: Tumour SUVmax on diagnostic PSMA‐PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP. [ABSTRACT FROM AUTHOR]

One of the most reliable features of natural systems is that they change through time. Theory predicts that temporally fluctuating conditions shape community composition, species distribution patterns, and life history variation, yet features of temporal variability are rarely incorporated into studies of species–environment associations. In this study, we evaluated how two components of temporal environmental variation—variability and predictability—impact plant community composition and species distribution patterns in the alpine tundra of the Southern Rocky Mountains in Colorado (USA). Using the Sensor Network Array at the Niwot Ridge Long‐Term Ecological Research site, we used in situ, high‐resolution temporal measurements of soil moisture and temperature from 13 locations ("nodes") distributed throughout an alpine catchment to characterize the annual mean, variability, and predictability in these variables in each of four consecutive years. We combined these data with annual vegetation surveys at each node to evaluate whether variability over short (within‐day) and seasonal (2‐ to 4‐month) timescales could predict patterns in plant community composition, species distributions, and species abundances better than models that considered average annual conditions alone. We found that metrics for variability and predictability in soil moisture and soil temperature, at both daily and seasonal timescales, improved our ability to explain spatial variation in alpine plant community composition. Daily variability in soil moisture and temperature, along with seasonal predictability in soil moisture, was particularly important in predicting community composition and species occurrences. These results indicate that the magnitude and patterns of fluctuations in soil moisture and temperature are important predictors of community composition and plant distribution patterns in alpine plant communities. More broadly, these results highlight that components of temporal change provide important niche axes that can partition species with different growth and life history strategies along environmental gradients in heterogeneous landscapes. [ABSTRACT FROM AUTHOR]

Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight‐based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity. Dexamethasone was given as either IV or oral/enteral administration, and a salt factor correction was used for dexamethasone sodium phosphate injection. A PopPK analysis using dexamethasone plasma concentration versus time was performed using the software NONMEM. A virtual population of 1000 children with obesity across three age groups was generated for dosing simulations. Data from 59 study participants with 82 PK plasma samples were used in the PopPK analysis. A one‐compartment model with first‐order absorption and the inclusion of total body weight as a covariate characterized the data. No other covariates were included in the PopPK model. Single and multiple IV dose(s) of 0.5 and 1 mg/kg every 8 h resulted in 68% or more of virtual children with obesity attaining simulated exposures that were within exposure ranges previously reported in adult studies. In conclusion, this was the first study to characterize dexamethasone's PopPK in children with obesity. Simulation results suggest that virtual children with obesity receiving oral doses of 0.5 and 1 mg/kg had generally comparable dexamethasone exposures as adult estimates. Additional studies are needed to characterize the dexamethasone's target exposure in children. [ABSTRACT FROM AUTHOR]

Aims: Superficial CD34‐positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low‐grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types. Methods and Results: Forty cases of atypical FH were retrieved, including CD34‐positive tumours (n = 20) and CD34‐negative tumours (n = 20). All tumours were stained for CADM3. All CADM3‐positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34‐positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34‐negative atypical FH were CADM3‐positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton‐like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement. Conclusion: A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify variables that predict gout remission in people with erosive gout receiving urate‐lowering therapy. Methods: We analyzed data from a two‐year, double‐masked randomized‐controlled trial of people with erosive gout, randomized to a serum urate target of <0.20 mmol/L or <0.30 mmol/L using oral urate‐lowering therapies. All participants had dual‐energy computed tomography (DECT) scans of the feet and ankles at baseline. The proportion of participants achieving gout remission according to the 2016 preliminary gout remission criteria and simplified gout remission criteria (without the patient reported outcomes) was analyzed. Logistic regression models were used to evaluate predictors of gout remission in year 2. Results: The preliminary gout remission criteria were fulfilled in 11 of 97 participants (11%) at year 1 and 21 of 92 participants (23%) at year 2. The simplified criteria were fulfilled in 26 of 97 participants (27%) in year 1 and 40 of 92 participants (44%) in year 2. In multivariable regression models, baseline DECT monosodium urate crystal volume was the only significant independent predictor of gout remission at year 2, using either criteria. Each 1‐cm3 increase in the baseline DECT monosodium urate crystal volume decreased the odds of fulfilling the 2016 preliminary gout remission criteria (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.46–0.93; P = 0.02) and the simplified gout remission criteria (OR 0.57, 95% CI 0.41–0.78; P < 0.001). Conclusion: In people with erosive gout on urate‐lowering therapy, higher baseline DECT monosodium urate crystal volume is associated with lower odds of gout remission after two years of treatment, defined by either the preliminary gout remission criteria or simplified gout remission criteria. [ABSTRACT FROM AUTHOR]

In a world of increasing complexity, I propose that the concept of emotional intelligence is limited for understanding how people manage their family relationships and interactions with community systems. I review the background of the emotional intelligence concept and point out its limitations for dealing with multilateral relationships. I define systems intelligence as the capacity to effectively interact in multilateral relationships, including families, work groups, and social institutions. Systems intelligence encompasses the understanding of interpersonal systems, and the practical ability to act constructively in those systems. I also make a distinction between competency in dyadic relationships (relational intelligence) and competency in multilateral relationships (systems intelligence), and I illustrate systems intelligence with respect to stepfamilies and families' relationships with health‐care professionals. A principal implication for the family field is to move beyond a focus on dyads (parent/child and couple) to include multilateral relationships that are intrinsic to family life. [ABSTRACT FROM AUTHOR]

Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults. We examined how baseline tau PET, Aβ PET, and ApoE4 genotype status interact with rsFC between hippocampus and these downstream regions to predict rate of tau accumulation in neocortex. We found that the 3‐way interaction between connectivity, baseline tau, and baseline Aβ or ApoE4 status was associated with neocortical tau accumulation in precuneus and inferior temporal cortex. In addition, baseline tau, Aβ, and ApoE4 status also moderated the association between connectivity and rate of memory decline. Together, these results suggest that the extent and distribution of future tau accumulation may be predicted by the interaction of baseline connectivity, AD pathology, and genetic risk. [ABSTRACT FROM AUTHOR]

Understanding factors influencing carbon effluxes from soils to the atmosphere is important in a world experiencing climatic change. Two important uncertainties related to soil organic carbon (SOC) stock responses to a changing climate are (a) whether soil microbial communities acclimate or adapt to changes in soil temperature and (b) how to represent this process in SOC models. To further explore these issues, we included thermal adaptation of enzyme‐mediated processes in a mechanistic SOC model (ReSOM) using the macromolecular rate theory. Thermal adaptation is defined here to encompass all potential responses of soil microbes and microbial communities following a change in temperature. To assess the effects of thermal adaptation of enzyme‐mediated processes on simulated SOC losses, ReSOM was applied to data collected from a 13‐year soil warming experiment. Results show that a model omitting thermal adaptation of enzyme‐mediated processes substantially overestimates observed CO2 effluxes during the initial years of soil warming. The bias against observed CO2 effluxes was lower for models including thermal adaptation of enzyme‐mediated processes. In addition, for a simulated linear 3°C soil warming over 100 years, models including thermal adaptation of enzyme‐mediated processes simulated SOC losses of a factor of three smaller than models omitting this process. As thermal adaptation of microbial community characteristics is generally not included in models simulating feedback between the soil, biosphere and atmosphere, we encourage future studies to assess the potential impact that microbial adaptation has on soil carbon – climate feedback representations in models. Plain Language Summary: A major uncertainty in projecting how much soil organic carbon (SOC) will be converted to CO2 as a consequence of climate change is related to how soil microbes may adapt to increasing soil temperatures. While this "microbial thermal adaptation" has been shown to occur in short‐term lab incubation experiments, its effect on SOC cycling on a decadal timescale is not clear. To address this knowledge gap, a mechanistic SOC model was used to simulate data collected from a 13‐year soil warming experiment, to assess how microbial thermal adaptation affects predicted SOC losses upon soil warming. The model results show that incorporating microbial thermal adaptation into the model led to reduced CO2 effluxes from the soil to the atmosphere compared to the common approach of omitting this mechanism. Our results imply that projected SOC losses for the decades to come may be reduced when this mechanism is incorporated in land models. We therefore advocate for more research on the mechanisms controlling microbial thermal adaptation, and how to implement this mechanism in SOC models. Key Points: A crucial aspect of soil organic carbon (SOC) models is the representation of soil microbesPredicted soil CO2 fluxes upon soil warming are reduced when accounting for microbial thermal adaptationOn a centennial time scale, this thermal adaptation results in up to a factor of three lower predicted SOC loss [ABSTRACT FROM AUTHOR]

This study showcases a global, heterogeneously coupled total water level system wherein salinity and temperature outputs from a coarser‐resolution (∼ ${\sim} $12 km) ocean general circulation model are used to calculate density‐driven terms within a global, higher‐resolution (∼ ${\sim} $2.5 km) depth‐averaged total water level model. We demonstrate that the inclusion of baroclinic forcing in the barotropic model requires modification of the internal wave drag term to prevent excess degradation of tidal results compared to the barotropic model. By scaling the internal tide dissipation by an easy to calculate dissipation ratio, the resulting heterogeneously coupled model has complex root mean square errors (RMSE) of 2.27 cm in the deep ocean and 12.16 cm in shallow waters for the M2 ${\mathrm{M}}_{2}$ tidal constituent. While this represents a 10%–20% deterioration as compared to the barotropic model, the improvements in total water level prediction more than offset this degradation. Global median RMSE compared to observations of total water levels, 30‐day sea levels, and non‐tidal residuals improve by 1.86 (18.5%), 2.55 (42.5%), and 0.36 (5.3%) cm respectively. The drastic improvement in model performance highlights the importance of including density‐driven effects within global hydrodynamic models and will help to improve the results of both hindcasts and forecasts in modeling extreme and nuisance flooding. With only an 11% increase in model run time compared to the fully barotropic total water level model, this approach paves the way for high resolution coastal water level and flood models to be used alongside climate models, improving operational forecasting of total water levels. Plain Language Summary: We showcase a total water level model wherein data from a lower‐resolution, 3D ocean model is used to capture changes in density within a higher‐resolution 2D total water level model. The inclusion of density‐driven effects within the 2D model changes the dynamics of the ocean and necessitates modifications to the internal tide dissipation parameterization in order to accurately capture tides in the coupled system. While purely tidal results are degraded by 10%–20% as compared to the non‐coupled model, the resulting system more accurately predicts water levels due to tides, winds, and atmospheric pressure (18%); 30‐day mean sea levels (42%); and the meteorologically driven water levels (5%). These improvements help to more accurately predict water levels due to storm events—including hurricanes and tropical cyclones—as well as less deadly but still disruptive flooding seen in coastal communities caused by rising sea levels. Key Points: Scaling internal tide dissipation to occur at tidal frequencies, drastically improving global tides in a heterogeneously coupled systemBaroclinic forcing from an external ocean model improves accuracy of a barotropic model and allows for the capture of long‐term sea levelsHeterogeneous coupling with an ocean global circulation model and a barotropic model efficiently captures density‐driven effects [ABSTRACT FROM AUTHOR]

Objective: Janus kinase family members are essential for signaling by multiple cytokines, including many implicated in systemic lupus erythematosus (SLE) pathogenesis. To test whether inhibition of JAK1 signaling can be efficacious in SLE, we used a JAK1‐selective inhibitor (ABT‐317) and evaluated its ability to ameliorate disease in murine SLE. Methods: Efficacy of ABT‐317 was evaluated using NZB/W‐F1 mice treated prophylactically and therapeutically. Primary endpoints were proteinuria, survival, and saliva production. Other endpoints included histological analysis of kidneys and salivary glands, flow cytometric analysis of splenic cell populations, and gene expression analysis by RNA sequencing in the kidneys, salivary glands, and blood. Publicly available human kidney gene transcription data were used to assess the translatability of the mouse findings. Results: ABT‐317 was efficacious when dosed prophylactically and prevented disease for up to two months after treatment cessation. When dosed therapeutically, ABT‐317 quickly reversed severe proteinuria and restored saliva production, as well as diminished kidney and salivary gland inflammation. ABT‐317‐induced changes in glomerular morphology coincided with normalization of a human nephrotic gene signature, suggesting translatability to human lupus nephritis (LN). Conclusion: JAK1 inhibition prevented and reversed kidney and salivary gland manifestations of murine lupus with long‐lasting effects after treatment cessation. These data, along with the presence of JAK1 and nephrotic gene signatures in human LN glomeruli, suggest that a JAK1‐selective inhibitor may be an effective therapeutic in the treatment of human SLE and LN. [ABSTRACT FROM AUTHOR]

Global average upper atmosphere temperature changes linked with the Hunga volcanic eruption (January 2022) are analyzed based on satellite measurements and compared with chemistry‐climate model simulations. Results show stratospheric cooling of −0.5 to −1.0 K in the middle and upper stratosphere during 2022 through middle 2023, followed by stronger cooling (−1.0 to −2.0 K) in the mesosphere after middle 2023. The cooling patterns follow the upward propagating water vapor (H2O) anomalies from Hunga, and similar behavior is found between observations and model simulations. While the stratospheric cooling is mainly due to radiative cooling from enhanced H2O, the mesospheric temperature changes result from ozone losses in the mesosphere, which are in‐turn driven by HOx radicals from Hunga H2O. Comparisons with the multi‐decade climate record show that Hunga impacts on stratospheric temperatures have similar magnitude, but opposite sign, to temperature effects from the large El Chichón (1982) and Pinatubo (1991) volcanic eruptions. Plain Language Summary: We analyze temperature changes in the upper atmosphere due to the Hunga volcanic eruption in January 2022 using satellite observations and simulations from a state‐of‐the‐art chemistry‐climate model. Hunga was an underwater volcano that emitted a large amount of water vapor (H2O) directly into the stratosphere, and this H2O has moved slowly upwards over time and mostly remains in the upper atmosphere. Observations show cooling of the stratosphere (20–50 km) by 0.5–1.0 K during 2022 to middle 2023, and cooling of the mesosphere (50–80 km) by 1.0–2.0 K after middle 2023. The cooling patterns follow the upward moving Hunga H2O plume. The model simulations show good agreement with observations, and the model is used to diagnose that the cooling is due to Hunga H2O impacts. The long‐lasting, global‐scale cooling from Hunga has similar magnitude, but opposite sign, to stratospheric warming observed from previous large volcanic eruptions (El Chichón in 1982 and Pinatubo in 1991); the differences are due to the large H2O emitted by Hunga. Key Points: Global average cooling of 1–2 K is observed in the upper atmosphere during 2022–2024 following Hunga eruption in January 2022Good agreement of observations with chemistry‐climate model simulations; cooling is mainly due to Hunga H2O impactsHunga‐forced cooling is comparable in magnitude to stratospheric warming following El Chichón (1982) and Pinatubo (1991) eruptions [ABSTRACT FROM AUTHOR]

Stratospheric transit time distributions (age‐of‐air spectra) are estimated using time series of satellite water vapor (H2O) measurements from the Microwave Limb Sounder over 2004 to 2021 assuming stationary transport. Latitude‐altitude dependent spectra are derived from correlations of interannual H2O anomalies with respect to the tropical tropopause source region, fitted with an inverse Gaussian distribution function. The reconstructions accurately capture interannual H2O variability in the "tropical pipe" and near‐global lower stratosphere, regions of relatively fast transport (∼1–2 years) in the Brewer‐Dobson circulation. The calculations provide novel observational estimates of the corresponding "short transit‐time" part of the age spectrum in these regions, including the mode. However, the H2O results do not constrain the longer transit‐time "tail" of the age spectra, and the mean age of air and spectral widths are systematically underestimated compared to other data. We compare observational results with parallel calculations applied to the WACCM chemistry‐climate model and the CLaMS chemistry‐transport model, and additionally evaluate the method in CLaMS by comparing with spectra from idealized pulse tracers. Because the age spectra accurately capture H2O interannual variations originating from the tropical tropopause, they can be used to identify "other" sources of variability in the lower stratosphere, and we use these calculations to quantify H2O anomalies in the Southern Hemisphere linked to the Australian New Years fires in early 2020 and the Hunga volcanic eruption in 2022. Plain Language Summary: Stratospheric water vapor (H2O) is mainly controlled by transport across the cold tropical tropopause, which sets the entry value for the global stratosphere. Interannual variations in H2O originate near the tropical tropopause and then propagate throughout the stratosphere with the global Brewer‐Dobson circulation (BDC), where anomalies are lagged in time and smoothed by mixing. We use the observed time series of H2O from the Microwave Limb Sounder during 2004–2021 to calculate transit time distributions (also called age spectra) from the tropical tropopause source region. The results capture H2O variability in the tropics up to 30 km and in the global lower stratosphere, regions of relatively fast transport (∼1–2 years) in the BDC. The calculations provide novel observational estimates of the age spectra in these regions. The calculations are straightforward to apply to global models, and we compare observational results with simulations from the WACCM and CLaMS models. Key Points: Stratospheric transit time distributions (age spectra) are derived from time series of satellite water vapor measurementsWater vapor reconstructions from age spectra capture detailed variability in the tropics up to 30 km and in the global lower stratosphereAge spectrum results are compared between observations and global model simulations [ABSTRACT FROM AUTHOR]

Solid‐state emission is pivotal for the functionality of organic compounds in opto‐electronic applications. Yet, tailoring the emission characteristics of existing solid‐state emissive organic frameworks is a challenging task, primarily due to their intricate structure‐activity interplay. In this study, an innovative family of solid‐state luminogens, centered around the dibenzosuberenylidene core are introduced. These luminogens are characterized by a remarkable excited‐state aromatization‐induced structural planarization (ESAISP) behavior. This unique feature allows for the modulation of their fluorescence properties, including color and intensity, through simple structural alterations, opening new avenues in the development of organic advanced functional materials. [ABSTRACT FROM AUTHOR]

ABSTRACT The lower Nama Group in southern Namibia contains trace fossils and soft‐bodied and biomineralized macro‐organisms from the terminal Ediacaran Period (ca 550 to 539 Ma), offering insights into early metazoan evolution. Interpretation of the fossilized Nama Group organisms as being preserved in, or very close to, the environments in which they originally lived has yielded insights into organism feeding habits, reproduction and life histories. Sedimentological evidence presented here reveals that typical ‘Nama‐type’ Ediacaran macro‐fossils (Cloudina, Ernietta, Pteridinium and Rangea) in the Dabis and Zaris formations of the Witputz Sub‐basin seldom preserve organisms in life position in their original palaeoenvironments. Both soft‐bodied and biomineralizing organisms were transported in sediment gravity flows (debris flows, turbidity flows and transitional debris flow‐turbidity flow ‘hybrid’ event beds) or combined flow (hummocky cross‐strata) to their terminal environment of deposition in shoreface and offshore shelf settings. Transport has placed studied beds and their associated macro‐organisms in depositional settings detached from the original life habitat, with macro‐organisms sourced from shallower‐water, up‐slope environments. Integrated sedimentological and palaeontological data indicate that the Nama Group may not provide a high‐fidelity record of original Nama ecosystems. Individual macro‐organisms are clasts within beds, and can be horizontal, imbricated or chaotic in orientation. Transport can blend different communities at various scales (bed, outcrop and basin), complicating interpretations of life habitats, species interactions and taxon‐specific ecology, such as feeding behaviour and life position of organisms. Recognition of organism transport also impacts datasets used for comparing global Ediacaran fossil assemblages, with implications for tracking spatial and temporal patterns in early animal evolution. [ABSTRACT FROM AUTHOR]

Cities are particularly vulnerable to surface water flooding. It is also well‐known that they influence local rainfall themselves, which has important implications for climate change adaptation planning for cities. At km‐scale resolution, convection‐permitting climate models (CPCMs) better resolve cities and should better represent local urban temperature and rainfall modifications. However, using state‐of‐the‐art pan‐African CPCM simulations with the Met Office Unified Model (CP4), we show that for the city of Johannesburg, South Africa, this is not the case. A significant enhancement of rainfall occurs over the city compared with surrounding rural areas, which is not seen in available observations. We demonstrate this is associated with an overestimated urban heat island effect, which leads to additional triggering of rainfall. Urban signals in future rainfall change are small compared with changes in the wider surroundings, the latter of which we expect to be more reliable than in models with parameterized convection. This suggests that deficiencies in representation of urban processes are of secondary importance in terms of future percentage change in rainfall. We recommend urban planners apply relative changes in CP4 as an uplift to observations, where available, or treat absolute future rainfall as an upper estimate if used directly. [ABSTRACT FROM AUTHOR]

Languages vary in their complexity; caregivers vary in the way they structure their communicative interactions with children; and boys and girls can differ in their language skills. Using a multilevel modelling approach, we explored how these factors influence the path of language acquisition for young children growing up around the world (mean age 2‐years 9‐months; 56 girls). Across 43 different sites, we analysed 103 mother–child pairs who spoke 3,170,633 utterances, 16,209,659 morphemes, divided across 20 different languages: Afrikaans, Catalan, Cantonese, Danish, Dutch, English, Farsi, French, German, Hebrew, Icelandic, Irish, Italian, Japanese, Mandarin, Norwegian, Portuguese, Spanish, Swedish and Turkish. Using mean length of utterance (MLU) as a measure of language complexity and developmental skill, we found that variation in children's MLU was significantly explained by (a) between‐language differences; namely the rate of child MLU growth was attuned to the complexity of their mother tongue, and (b) between‐mother differences; namely mothers who used higher MLUs tended to have children with higher MLUs, regardless of which language they were learning and especially in the very young (<2.5 years‐old). Controlling for family and language environment, we found no evidence of MLU sex differences in child speech nor in the speech addressed to boys and girls. By modelling language as a multilevel structure with cross‐cultural variation, we were able to disentangle those factors that make children's pathway to language different and those that make it alike. Research Highlights: The speech of 103 mother–child pairs from 20 different languages showed large variation in the path of early language development.Language, family, but not the sex of the child, accounted for a significant proportion of individual differences in child speech, especially in the very young.The rate at which children learned language was attuned to the complexity of their mother tongue, with steeper trajectories for more complex language.Results demonstrate the relative influence of culture, family, and sex in shaping the path of language acquisition for different children. [ABSTRACT FROM AUTHOR]

Photosynthesis is the largest flux of carbon between the atmosphere and Earth's surface and is driven by enzymes that require nitrogen, namely, ribulose‐1,5‐bisphosphate (RuBisCO). Thus, photosynthesis is a key link between the terrestrial carbon and nitrogen cycle, and the representation of this link is critical for coupled carbon‐nitrogen land surface models. Models and observations suggest that soil nitrogen availability can limit plant productivity increases under elevated CO2. Plants acclimate to elevated CO2 by downregulating RuBisCO and thus nitrogen in leaves, but this acclimation response is not currently included in land surface models. Acclimation of photosynthesis to CO2 can be simulated by the photosynthetic optimality theory in a way that matches observations. Here, we incorporated this theory into the land surface component of the Energy Exascale Earth System Model (ELM). We simulated land surface carbon and nitrogen processes under future elevated CO2 conditions to 2100 using the RCP8.5 high emission scenario. Our simulations showed that when photosynthetic acclimation is considered, photosynthesis increases under future conditions, but maximum RuBisCO carboxylation and thus photosynthetic nitrogen demand decline. We analyzed two simulations that differed as to whether the saved nitrogen could be used in other parts of the plant. The allocation of saved leaf nitrogen to other parts of the plant led to (1) a direct alleviation of plant nitrogen limitation through reduced leaf nitrogen requirements and (2) an indirect reduction in plant nitrogen limitation through an enhancement of root growth that led to increased plant nitrogen uptake. As a result, reallocation of saved leaf nitrogen increased ecosystem carbon stocks by 50.3% in 2100 as compared to a simulation without reallocation of saved leaf nitrogen. These results suggest that land surface models may overestimate future ecosystem nitrogen limitation if they do not incorporate leaf nitrogen savings resulting from photosynthetic acclimation to elevated CO2. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off‐label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High‐performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two‐compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <−.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine. [ABSTRACT FROM AUTHOR]

Intranasal insulin is a putative neuroprotective therapy after cardiac arrest, but safety in humans at doses extrapolated from animal models is unknown. This phase I, open‐label adaptive dose‐escalation study explores the maximum tolerated dose of intranasal insulin in healthy human participants. Placebo or insulin at doses from 0 to 1000 units was given to healthy participants intranasally on repeated weekly visits. Serum glucose, insulin, and C‐peptide levels were measured serially at 0, 15, 30, 60, 120, 180, and 240 min after administration. Twenty‐four participants (12 female, median age 53, IQR 35–61) were enrolled. There was minimal change in average serum glucose after administration of intranasal insulin. Average serum insulin increased slightly in a dose‐dependent manner, reaching maximum concentrations at 15 min. C‐peptide decreased over time from administration in all groups. One participant had severe hypoglycemia (24 mg/dL at 45 min) and a different participant had mild hypoglycemia (51 mg/dL at 30 min), both after receiving 600 U intranasal insulin. Hypoglycemic episodes were associated with increases in serum insulin. Both participants continued in the study without hypoglycemia after additional doses. High‐dose intranasal insulin up to 1000 U was generally well tolerated, with minimal measurable systemic absorption and without significant aggregate changes in mean glucose. Idiosyncratic episodic systemic absorption and hypoglycemia require further study and additional caution in potential clinical application. Further study of its target engagement and efficacy as a neuroprotective therapy after cardiac arrest at these doses is warranted. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) are effective surgeries to treat end‐stage knee osteoarthritis. Clinicians assume that TKA alters knee kinematics while UKA preserves native knee kinematics; however, few studies of in vivo kinematics have evaluated this assumption. This study used biplane radiography to compare side‐to‐side tibiofemoral kinematics during chair rise, stair ascent, and walking in 16 patients who received either TKA or UKA. We hypothesized that TKA knees would have significant kinematic changes and increased asymmetry with the contralateral knee, while UKA knee kinematics would not change after surgery and preoperative knee symmetry would be maintained. Native bone and implant motion were tracked using a volumetric model‐based tracking technique. Six degrees of freedom kinematics were calculated throughout each motion. Kinematics were compared between the operated and contralateral knees pre‐ and post‐surgery using a linear mixed‐effects model. TKA knees became less varus with the tibia more medial, posterior, and distal relative to the femur. UKA knees became less varus with the tibia less lateral on average. Postoperative TKA knees were in less varus than UKA knees on average and at low flexion angles, with an internally rotated tibia during chair rise and stair ascent. At high flexion angles, the tibia was more medial and posterior after TKA than UKA. Side‐to‐side kinematic symmetry worsened after TKA but was maintained or improved after UKA. Greater understanding of kinematic differences between operated and contralateral knees after surgery may help surgeons understand why some patients remain unsatisfied with their new knees. [ABSTRACT FROM AUTHOR]

Background: Critical care pharmacists are well‐established, valuable members of the intensive care unit interprofessional team with unique skills to perform comprehensive medication management in complex critically ill patients. However, standardized and consequential productivity metrics for critical care pharmacists have not been established. Objective: To characterize the utilization and perception of contemporary critical care pharmacy productivity metrics utilized among individual institutions. Design, Setting, and Participants: An electronic survey was distributed to critical care pharmacist members of the Society of Critical Care Medicine Clinical Pharmacy and Pharmacology Section and the American College of Clinical Pharmacy Critical Care Practice and Research Network. Main Outcomes and Measures: The survey included 23 questions to assess institution demographics, individual respondent demographics, institution practices, and individual respondent perceptions about the value of critical care pharmacist productivity metrics. Results: A total of 204 critical care pharmacists, largely from the United States, responded to the survey between July and November 2022. Institutional metrics captured by more than 50% of the respondents' institutions included order verification rate/number of orders verified (60%), number of clinical interventions (57%), and intravenous to enteral product interchanges (52%). Of these metrics, critical care pharmacists only agreed with the value of the number of clinical interventions, were indifferent to the value of intravenous to oral product interchanges, and disagreed with the value of order verification rate/number of orders verified. Conclusions: Significant discrepancies exist between institutional productivity metric practices and their perceived value and utility among critical care pharmacists. [ABSTRACT FROM AUTHOR]

A practical approach for modeling field‐scale moisture flow in a highly heterogeneous unsaturated medium is described in this study. The validity of this approach is demonstrated through comparison of the numerical simulations with field observations at a semiarid site located in southcentral Washington State. The methodology is based on upscaling the core scale hydraulic properties and combining power‐law and tensorial connectivity‐tortuosity (PA‐TCT) approaches to derive macroscopic anisotropy parameters for each hydrostratigraphic unit (HSU) identified in the field. Each heterogeneous HSU is approximated by an equivalent homogeneous medium (EHM) model for which PA‐TCT parameters are used in the flow simulations. The available field data on moisture content and matric potential are compared with steady‐state flow simulations based on the mean form of Richards' equation. While the homogenization or averaging of heterogeneities, embedded in the EHM modeling approximation, cannot capture all of the field‐scale variability, the simulated steady‐state moisture and matric potential profiles capture well the central tendency of the field data. This approach is deemed practical for assessing the fate and transport of contaminants in highly heterogeneous unsaturated media at the transport scale of hundreds of meters. Core Ideas: Numerical simulation results of field‐scale moisture flow are compared with field observations.Directional dependence of pore‐scale tortuosity‐connectivity leads to unsaturated K macroscopic anisotropy.Ensemble averaged Richards equation steady‐state simulations capture well the central tendency of field data. Plain Language Summary: A practical approach for modeling field‐scale moisture flow in a highly heterogeneous unsaturated medium is described in this study. The validity of this approach is demonstrated through comparison of the numerical simulations with field observations at a semiarid site located in southcentral Washington State. [ABSTRACT FROM AUTHOR]

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4–6] vs MM 5 [4–6], adjusted generalized odds ratio 0.89 [0.53–1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3–6] vs MM 5 [4–6], adjusted generalized odds ratio 1.87 [1.45–2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887–894 [ABSTRACT FROM AUTHOR]

Background: To report the clinicopathological features and epidemiology of iris melanoma in Queensland, Australia. Methods: This was a retrospective study of 86 patients with iris melanoma treated between 2001 and 2022 at the Queensland Ocular Oncology Service, Brisbane, Australia. Main outcome measures included demographics, clinical and phenotypic features, age‐adjusted incidence and relative survival. Results: Eighty‐six patients (63% female) were included. Mean age was 54 years (range 17–82 years). The majority of patients (97%) were Caucasian, with blue eyes, fair skin and Fitzpatrick Skin Type I or II. Demographic features and clinical history showed a tendency for high ultraviolet radiation (UVR) exposure in the cohort. Histopathology was available in 69 cases (82%), and of these, 77% tumours were of spindle cell origin, with low‐risk genetic profiles. Patients were followed for a mean of 8 years (median 7, range 1–21 years) after diagnosis, and only one case of metastasis was documented. Conclusions: The association of iris freckles, history of UVR exposure and dermatologic findings supports the role of UVR in iris melanoma. Occupation and avocation history, as well as evaluation of iris freckles may offer an easily accessible way of stratifying the risk of an individual for development of UVR‐related uveal melanoma. [ABSTRACT FROM AUTHOR]

Objectives: To compare otolaryngology interview and match outcomes between applicants with and without home residency programs. Methods: Otolaryngology applicants from US allopathic medical schools during the 2019–2023 cycles who responded to the Texas Seeking Transparency in Application to Residency (STAR) survey were identified. Students were stratified based upon whether their medical school had an affiliated otolaryngology residency program. The primary outcomes were number of interviews and match rate. Wilcoxon‐rank sum and χ2 testing was used to assess associations between home program status and interview and match outcomes. Results: Of the 633 fourth‐year medical students applying to otolaryngology during the 2019–2023 application cycles, 89 had no home program (NHP) and 544 had a home program (HP). Applicants with NHP completed significantly more away rotations than applicants with a HP (2.2 vs. 1.5; p < 0.01). There was no difference in mean number of applications submitted between applicants with NHP and applicants with a HP. However, applicants with a HP received a significantly greater number of interviews (14.7 vs. 11.8; p < 0.01), attended more interviews (12.4 vs. 11.3; p = 0.02), attended a lower percentage of their offered interviews (84.4% vs. 95.8%), and had a higher match rate (81.8% vs. 70.8%; p = 0.02) than applicants with NHP. Applicants with NHP interviewed at (1.9 vs. 1.3; p < 0.01) and matched at (33.7% vs. 23.9%; p = 0.048) significantly more away rotation institutions than applicants with a HP. Conclusion: Applicants with NHP received fewer interviews and had lower match rates. Away rotations may be especially important for applicants with NHP. Level of Evidence: NA Laryngoscope, 134:4494–4500, 2024 [ABSTRACT FROM AUTHOR]

The article challenges traditional views on pronghorn habitat by highlighting the use of high-elevation summer ranges in the Carter Mountain area of the Greater Yellowstone Ecosystem in Wyoming. Through GPS tracking, researchers found that some pronghorn migrate to alpine meadows and plateaus above 3000m, a behavior previously considered anomalous. The study raises questions about the processes that generate and maintain diversity in animal movement tactics, emphasizing the need for further research to understand the implications of pronghorn using high-elevation habitats. The article acknowledges the Indigenous communities with cultural and spiritual ties to the region, respecting their connection to the land. [Extracted from the article]

Summary: Background: Nearly half of adult patients undergoing surgery experience moderate or severe postoperative pain. Inadequate pain management hampers postoperative recovery and function and may be associated with adverse outcomes. This multidisciplinary consensus statement provides principles that might aid postoperative recovery, and which should be applied throughout the entire peri‐operative pathway by healthcare professionals, institutions and patients. Methods: We conducted a directed literature review followed by a four‐round modified Delphi process to formulate recommendations for organisations and individuals. Results: We make recommendations for the entire peri‐operative period, covering pre‐admission; admission; intra‐operative; post‐anaesthetic care unit; ward; intensive care unit; preparation for discharge; and post‐discharge phases of care. We also provide generic principles of peri‐operative pain management that clinicians should consider throughout the peri‐operative pathway, including: assessing pain to facilitate function; use of multimodal analgesia, including regional anaesthesia; non‐pharmacological strategies; safe use of opioids; and use of protocols and training for staff in caring for patients with postoperative pain. Conclusions: We hope that with attention to these principles and their implementation, outcomes for adult patients having surgery might be improved. [ABSTRACT FROM AUTHOR]

N‐methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N‐dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine biosynthesis: TrpM, a tryptophan N‐methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N‐methylate the non‐native amino acid substrate, 4‐hydroxytryptophan, a key intermediate in the Escherichia coli‐based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N‐dimethyl‐4‐hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N‐methylated and 4‐hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products. [ABSTRACT FROM AUTHOR]

ABSTRACT Regional factors correlated with recruitment of black bass (largemouth bass; Micropterus nigricans and smallmouth bass; Micropterus dolomieu), two important fishes, are rarely studied, despite the importance of recruitment variation in influencing fish populations. We sought to identify factors that drove variation in age‐0 and age‐1 black bass abundance. Age‐0 or age‐1 black bass catch per unit effort (CPUE) in reservoirs in Kansas and Illinois, USA, was positively correlated with local short‐term (i.e., mean April precipitation) environmental variables. In contrast, age‐0 or age‐1 black bass CPUE was generally negatively correlated with long‐term environmental variables and river regulation metrics (i.e., reservoir elevation) in the Mississippi and Missouri river reservoirs. Our findings highlight that consideration of spatiotemporal scale is important when managing black bass populations. [ABSTRACT FROM AUTHOR]

ABSTRACT The importance of state capacity and institutional quality has received significant attention within the academic literature. This is especially true as it relates to the protection of property rights and, ultimately, the role it plays in economic development. This study adds to this literature by considering how lynching activity across US states impacts sovereign credit. Given that lynching tends to be associated with weak public‐sector institutions, limited‐access social orders, and the weak protection of individual and property rights, we posit that as lynchings increase so too will bond yields. The analysis covers the period 1883–1920 and find support that state borrowing costs rose as lynching activity increased. The results are robust to a number of specifications, demographic groups, and regions. Implications are discussed. [ABSTRACT FROM AUTHOR]

The demands of a sustainable chemical industry are a driving force for the development of heterogeneous catalytic platforms exhibiting facile catalyst recovery, recycling, and resilience to diverse reaction conditions. Homogeneous‐to‐heterogeneous catalyst transitions can be realized through the integration of efficient homogeneous catalysts within porous matrices. Herein, we offer a versatile approach to understanding how guest distribution and evolution impact the catalytic performance of heterogeneous host–guest catalytic platforms by implementing the resonance energy transfer (RET) concept using fluorescent model systems mimicking the steric constraints of targeted catalysts. Using the RET‐based methodology, we mapped condition‐dependent guest (re)distribution within a porous support on the example of modular matrices such as metal–organic frameworks (MOFs). Furthermore, we correlate RET results performed on the model systems with the catalytic performance of two MOF‐encapsulated catalysts used to promote CO2 hydrogenation and ring‐closing metathesis. Guests are incorporated using aperture‐opening encapsulation, and catalyst redistribution is not observed under practical reaction conditions, showcasing a pathway to advance catalyst recyclability in the case of host–guest platforms. These studies represent the first generalizable approach for mapping the guest distribution in heterogeneous host–guest catalytic systems, providing a foundation for predicting and tailoring the performance of catalysts integrated into various porous supports. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4–25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography‐mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age‐associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age‐associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non‐ambulant subjects, suggesting a threshold of 18–22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. Key points: The non‐invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non‐ambulant patients.The difference in %MM between ambulant and non‐ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM.The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability. [ABSTRACT FROM AUTHOR]

2D metal oxides (2DMOs) have recently emerged as a high‐performance class of ultrathin, wide bandgap materials offering exceptional electrical and optical properties for a wide area of device applications in energy, sensing, and display technologies. Liquid metal printing represents a thermodynamically advantageous strategy for synthesizing 2DMOs by a solvent‐free and vacuum‐free scalable method. Here, recent progress in the field of liquid metal printed 2D oxides is reviewed, considering how the physics of Cabrera‐Mott oxidation gives this rapid, low‐temperature process advantages over alternatives such as sol‐gel and nanoparticle processing. The growth, composition, and crystallinity of a burgeoning set of 1–3 nm thick liquid metal printed semiconducting, conducting, and dielectric oxides are analyzed that are uniquely suited for the fabrication of high‐performance flexible electronics. The advantages and limitations of these strategies are considered, highlighting opportunities to amplify the impact of 2DMO through large‐area printing, the design of doped metal alloys, stacking of 2DMO to electrostatically engineer new oxide heterostructures, and implementation of 2D oxide devices for gas sensing, photodetection, and neuromorphic computing. [ABSTRACT FROM AUTHOR]

This perspective provides an overview of issues needed to bring a testosterone‐progestogen combined transdermal male hormonal contraceptive to the market. Large‐scale phase 2b trials are near completion and a pivotal trial to confirm efficacy and safety has been designed. We believe we are close to accomplishing the steps necessary to bring the first male‐directed effective, safe, and reversible pharmaceutical contraceptive approach to the public. If successful, we believe it will provide a new option for couples to consider in their family planning. [ABSTRACT FROM AUTHOR]

The Alzheimer's Disease Neuroimaging Initiative (ADNI) PET Core has evolved over time, beginning with positron emission tomography (PET) imaging of a subsample of participants with [18F]fluorodeoxyglucose (FDG)‐PET, adding tracers for measurement of β‐amyloid, followed by tau tracers. This review examines the evolution of the ADNI PET Core, the novel aspects of PET imaging in each stage of ADNI, and gives an accounting of PET images available in the ADNI database. The ADNI PET Core has been and continues to be a rich resource that provides quantitative PET data and preprocessed PET images to the scientific community, allowing interrogation of both basic and clinically relevant questions. By standardizing methods across different PET scanners and multiple PET tracers, the Core has demonstrated the feasibility of large‐scale, multi‐center PET studies. Data managed and disseminated by the PET Core has been critical to defining pathophysiological models of Alzheimer's disease (AD) and helped to drive methods used in modern therapeutic trials. Highlights: The ADNI PET Core began with FDG‐PET and now includes three amyloid and three tau PET ligands.The PET Core has standardized acquisition and analysis of multitracer PET images.The ADNI PET Core helped to develop methods that have facilitated clinical trials in AD. [ABSTRACT FROM AUTHOR]

Background: There is a substantial research literature on identifying risk and protective factors for violence perpetration. Substance use disorders have long been identified as constituting a significant predictor of violent behaviour. Psychopathy traits have also been similarly recognised, but inter‐relationships between psychopathy traits, features of substance use disorders and violence have been little explored. Aims: To determine the degree to which shared variance between substance dependence symptoms and violence, as indicated by criminal charges for violent offences, among jailed men can be explained by psychopathy traits. Methods: Features of dependence on substances in three drug classes (alcohol, cannabis and cocaine) were assessed in a sample of 682 men in a county jail awaiting trial on criminal charges, many for violent offences. Statistical comparisons of zero‐order and partial correlations tested whether accounting for psychopathy total and facet scores, assessed by the Psychopathy Checklist‐Revised (PCL‐R), affected associations between substance dependence symptoms and violent charges. Results: Total PCL‐R scores accounted for a significant proportion of the shared variance between the history of criminal charges for violence offences and lifetime substance dependence symptoms in all three drug classes. At the facet level, controlling for ratings on the interpersonal and modified antisocial facets reduced the association between criminal charges for violent offences and symptoms of cocaine dependence; controlling for ratings on a modified antisocial facet also attenuated links between alcohol and cannabis dependence symptoms and history of charges for violent offences. Conclusion: These findings build on the sparse literature to date on the role of psychopathy traits on relationships between features of substance use disorders and violence. Given that the observed connection between substance dependence symptoms and charges for violent offences is partly accounted for by individual differences in psychopathy traits, it follows that effective treatment for those traits may be useful, perhaps essential to reducing links between features of some substance use disorders and violent offending. [ABSTRACT FROM AUTHOR]

Backgrounds: Despite a wide spectrum of contraceptive methods for women, the unintended pregnancy rate remains high (45% in the US), with 50% resulting in abortion. Currently, 20% of global contraceptive use is male‐directed, with a wide variation among countries due to limited availability and lack of efficacy. Worldwide studies indicate that >50% of men would opt to use a reversible method, and 90% of women would rely on their partner to use a contraceptive. Additional reasons for novel male contraceptive methods to be available include the increased life expectancy, sharing the reproductive risks among partners, social issues, the lack of pharma industry involvement and the lack of opinion makers advocating for male contraception. Aim: The present guidelines aim to review the status regarding male contraception, the current state of the art to support the clinical practice, recommend minimal requirements for new male contraceptive development and provide and grade updated, evidence‐based recommendations from the European Society of Andrology (EAA) and the American Society of Andrology (ASA). Methods: An expert panel of academicians appointed by the EAA and the ASA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Results: Sixty evidence‐based and graded recommendations were produced on couple‐centered communication, behaviors, barrier methods, semen analysis and contraceptive efficacy, physical agents, surgical methods, actions before initiating male contraception, hormonal methods, non‐hormonal methods, vaccines, and social and ethical considerations. Conclusion: As gender roles transform and gender equity is established in relationships, the male contribution to family planning must be facilitated. Efficient and safe male‐directed methods must be evaluated and introduced into clinical practice, preferably reversible, either hormonal or non‐hormonal. From a future perspective, identifying new hormonal combinations, suitable testicular targets, and emerging vas occlusion methods will produce novel molecules and products for male contraception. [ABSTRACT FROM AUTHOR]

Aims: Evidence on the relative impact of diverse genetic backgrounds associated with non‐ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long‐term outcomes of different gene groups in DCM. Methods and results: Electronic databases were systematically screened to identify studies reporting prognostic data on pre‐specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta‐analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67–2.65), MVAEs (OR 1.86, 95% CI 1.52–2.26), and HFEs (OR 2.01, 95% CI 1.08–3.73) than genotype‐negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20–2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non‐LMNA and non‐desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv. Conclusions: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM. [ABSTRACT FROM AUTHOR]