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This study aimed to investigate the simultaneous response of the cerebral and skeletal muscle microvasculature to the same phenylephrine (PE) boluses. A hybrid optical system that combines hyperspectral near‐infrared spectroscopy (hs‐NIRS) and diffuse correlation spectroscopy (DCS) was used to monitor changes in tissue oxygenation and perfusion. Data were collected from the head and hind limb of seven male Sprague–Dawley rats while administering intravenous (IV) injections of PE or saline to all animals. The response to saline was used as a control. Skeletal muscle oxygenation decreased significantly after PE injection, while a statistically underpowered decrease in perfusion was observed, followed by an increase beyond baseline. Vascular conductance also decreased in the muscle reflecting the drug's vasoconstrictive effects. Tissue oxygenation and perfusion increased in the brain in response to PE. Initially, there was a sharp increase in cerebral perfusion but no changes in cerebral vascular conductance. Subsequently, cerebral flow and vascular conductance decreased significantly below baseline, likely reflecting autoregulatory mechanisms to manage the excess flow. Further, fitting an exponential function to the secondary decrease in cerebral perfusion and increase in muscular blood flow revealed a quicker kinetic response in the brain to adjust blood flow. In the skeletal muscle, PE caused a transient decrease in blood volume due to vasoconstriction, which resulted in an overall decrease in hemoglobin content and tissue oxygen saturation. Since PE does not directly affect cerebral vessels, this peripheral vasoconstriction shunted blood into the brain, resulting in an initial increase in oxygenated hemoglobin and oxygen saturation. [ABSTRACT FROM AUTHOR]

Terrestrial processes influence the atmosphere by controlling land‐to‐atmosphere fluxes of energy, water, and carbon. Prior research has demonstrated that parameter uncertainty drives uncertainty in land surface fluxes. However, the influence of land process uncertainty on the climate system remains underexplored. Here, we quantify how assumptions about land processes impact climate using a perturbed parameter ensemble for 18 land parameters in the Community Earth System Model version 2 under preindustrial conditions. We find that an observationally‐informed range of land parameters generate biogeophysical feedbacks that significantly influence the mean climate state, largely by modifying evapotranspiration. Global mean land surface temperature ranges by 2.2°C across our ensemble (σ = 0.5°C) and precipitation changes were significant and spatially variable. Our analysis demonstrates that the impacts of land parameter uncertainty on surface fluxes propagate to the entire Earth system, and provides insights into where and how land process uncertainty influences climate. Plain Language Summary: Land processes can affect climate by controlling the transfer of energy and water from the land to the atmosphere. Previous research has shown that uncertainty surrounding land processes (e.g., photosynthesis and the movement of water through soils) can drive uncertainty in land‐to‐atmosphere fluxes. However, it remains unclear how much that land uncertainty can impact climate. Here, we quantify how climate is sensitive to assumptions about land processes by varying 18 land model parameters to create an ensemble of 36 possible worlds in a global climate model. Land temperature ranges by 2.2°C across this ensemble, mostly due to changes in how much water is evaporated from the land surface. Changing land parameters also drives regionally variable changes in mean precipitation. This study highlights a large and underappreciated impact of land processes in determining the mean climate state, and provides insights into how climate is influenced by land process uncertainty. Key Points: Land processes substantially impact the climatological mean state terrestrial temperature and precipitationLand parameters influence climate predominantly through changing evapotranspiration rather than through other mechanismsWarming driven by land processes activates different atmospheric feedbacks than radiatively‐driven warming [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Appropriate anticoagulation is crucial for the success of left ventricular assist device patients. Currently, there is no consensus on the optimal management of their subtherapeutic INR in ambulatory setting. Our goal is to evaluate both the short‐term adverse events and long‐term outcomes of enoxaparin bridging at a major transplant center, following the implementation of bridging safety criteria.In total, 85 patients' medical records were reviewed between 7/2019 and 5/2022, with 51 patients meeting safety criteria were bridged with enoxaparin and 34 non‐bridged. The primary endpoint was the occurrence of major bleeding/thrombosis events within 30 days of bridging. The secondary endpoint was freedom from events 30 days after enoxaparin initiation and overall patient survivability until the last follow‐up.Within 30 days, no major bleeding/thrombotic events were noted. After 30 days, the major bleeding rate was 5.8% in bridged vs. 11.8% in non‐bridged patients (p = 0.02). Overall, 3‐year survival was 78% in the bridged vs. 49% in non‐bridged patients (p < 0.001). In patients with no events, 3‐year survival was 80% in bridged vs. 58% in non‐bridged (p < 0.001). In the patients with bleeding events, 3‐year survival was 55% in bridged vs. 51% in non‐bridged (p = 0.11). At 1 year, freedom from bleeding in the bridged patients was 81% in patients with no events vs. 0% in those with an event (p < 0.0001).When eligibility criteria for safe bridging were applied, the use of enoxaparin bridging was associated with no major bleeding/thrombotic events during bridging and improved 3‐year survival in LVAD patients. Economically, using outpatient enoxaparin resulted in substantial healthcare savings, fewer readmissions, and improved quality of life. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol‐induced adaptations present in both human post‐mortem brains and reverse‐translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M4 and M5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype‐selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT Teachers’ beliefs about feedback can affect both the way they provide feedback and its effectiveness in improving students’ writing proficiency. However, research remains scant on belief–practice relationships. This study attempted to fill the gap by investigating such relationships with a sample of 112 Chinese university EFL teachers in teaching argumentative writing. Data were collected through a writing feedback beliefs and practices questionnaire, an argumentative writing teaching beliefs questionnaire, and semi‐structured interviews. The participants were selected using convenience sampling from six universities in Northern China. Quantitative data were analyzed through confirmatory factor analysis, multiple regression, and repeated measures ANOVA to examine the characteristics of these teachers’ writing feedback beliefs and the relationships between the beliefs and relevant practices. Qualitative data from the interviews were analyzed thematically to gain deeper insights into the belief–practice relationships. Results indicated that most teachers believed their feedback was crucial for improving students' argumentative writing, particularly regarding communicative purposes, discourse organization, linguistic expressions, argument construction, and rhetorical techniques. However, a discrepancy was noted between teachers' feedback beliefs and their practices, especially concerning linguistic expressions. These findings highlight the need for targeted support to better align teachers' feedback beliefs with their practices for more effective teaching of EFL writing. [ABSTRACT FROM AUTHOR]

Cordycepin (3′ deoxyadenosine) has been widely researched as a potential cancer therapy, but many diverse mechanisms of action have been proposed. Here, we confirm that cordycepin triphosphate is likely to be the active metabolite of cordycepin and that it consistently represses growth factor‐induced gene expression. Bioinformatic analysis, quantitative PCR and western blotting confirmed that cordycepin blocks the PI3K/AKT/mTOR and/or MEK/ERK pathways in six cell lines and that AMPK activation is not required. The effects of cordycepin on translation through mTOR pathway repression were detectable within 30 min, indicating a rapid process. These data therefore indicate that cordycepin has a universal mechanism of action, acting as cordycepin triphosphate on an as yet unknown target molecule involved in growth factor signalling. [ABSTRACT FROM AUTHOR]

ABSTRACT Positive emotions play a significant role in facilitating successful language learning by enhancing motivation, engagement, and overall academic achievements. Nonetheless, there remains a paucity of research exploring how language educators perceive and manifest positive emotions in the context of their teaching practices. This study endeavors to fill this gap by exploring the experiences, practices, and beliefs of language educators regarding positive emotions in effective teaching. Additionally, it seeks to elucidate the pedagogical strategies they associate with fostering conducive learning environments through the lens of Seligman's PERMA model. Employing thematic analysis of semi‐structured interviews with 60 Chinese language educators, the study uncovers key positive emotions integral to effective teaching, including passion, trust, joy, and empathy. Despite the prevalence of these positive emotions, teachers reported a diminished sense of meaning and accomplishment when instructing foreign languages in comparison to the engagement and relationship elements outlined in the PERMA model. The findings shed light on a spectrum of teaching strategies embraced by these educators that align with the components of the PERMA model. By illuminating the affective dimension of language teaching, this study not only provides valuable insights into understanding positive emotions, engagement, and relationships in language education but also offers practical implications for integrating PERMA elements into language teaching and learning practices. [ABSTRACT FROM AUTHOR]

Objective: Strokes involving sensory pathways can result in contralesional pain syndromes often refractory to pharmacologic interventions. Scrambler therapy (ST) is a noninvasive electroanalgesia device used to treat pain caused by peripheral neuropathy; however, data are scarce regarding its use in conditions secondary to central nervous system pathology. We evaluate the efficacy of ST to treat poststroke pain. Methods: Twenty patients with a history of prior stroke resulting in contralesional pain were randomized to receive ST or Sham as an adjunct to their stable medication regimen. Participants underwent 5 consecutive daily 40‐min sessions. The study was blinded to patient and assessor. Pain scores (0–10) were recorded at baseline, pre‐ and postsession, and 4 weeks after final treatment. Student's t‐tests compared differences in the mean change in pain score between groups immediately post‐treatment #5, and at 4‐weeks. The chi‐squared analysis compared the proportion of patients in each group with >50% pain reduction. Results: Participants randomized to ST had a mean change in pain score of −3.73 (SD 2.85) postintervention and −2.57 (SD 2.07) at 4 weeks, while the Sham group had a mean change in score of −0.94 (SD 1.36) and −0.25 (SD 0.84) (p between groups = 0.012, 0.004, respectively). Significantly more participants treated with ST reported a >50% reduction in pain immediately postintervention compared to Sham (70% vs. 10%, p = 0.006), but not at follow‐up (30% vs. 10%, p = ns). Interpretation: ST may effectively decrease poststroke pain compared to Sham. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications. [ABSTRACT FROM AUTHOR]

Understanding what facilitates and hinders water drinking is crucial to inform interventions for preventing underhydration. Using the Situated Assessment Method2, we extended previous research by examining what influences water drinking in daily life. We studied 213 UK adults, assessing 13 potential predictors (e.g. thirst, availability of other drinks) of their typical water intake across 10 everyday situations (e.g. during work, dinner). Participants then reported their actual water intake in these situations over three alternating days during a 1‐week follow‐up. We evaluated the variability of water intake and its influences across individuals and situations and the prospective relationship between these influences and water intake. The 13 identified predictors explained substantial proportions of variation in water intake. Factors like habitualness (e.g. subjective effort), self‐relevance (e.g. health consciousness) and immediate feedback (e.g. taste) were positively associated with water intake. However, the influence of these factors varied significantly across individuals and situations. Our results suggest that various interrelated predictors facilitate and hinder water drinking behaviour, emphasising the importance of using comprehensive behaviour theories to inform research in this domain. They also align with growing evidence that reward may regulate habitual behaviour. [ABSTRACT FROM AUTHOR]

Adolescent food insecurity is a salient adversity hypothesized to affect neural systems associated with increased impulsive behavior. Family environments shape how adverse experiences influence development. In this study, hypotheses were tested regarding the conjoint effects of food insecurity and family flexibility on impulsivity via alterations in connectivity between regions within the salience and central executive networks. Such alterations are reflected in resting‐state functional connectivity (rsFC) metrics between the anterior insula (AI) and the middle frontal gyrus (MFG). Hypotheses were tested in a longitudinal moderated mediation model with two waves of data from 142 adolescents (Time 1 [T1] Mage = 12.89, SD = 0.85; Time 2 [T2] Mage = 15.01, SD = 1.07). Data on past‐year household food insecurity, family flexibility, and rsFC were obtained at T1. Impulsivity was self‐reported by the adolescent at T1 and T2. Findings revealed that high T1 left‐to‐left rsFC between the AI and MFG was associated with increased impulsivity at T2. The interaction of family flexibility and food insecurity was associated with AI and MFG rsFC. In the context of low family flexibility, food insecurity was linked to high levels of AI and MFG rsFC. Conversely, in the context of optimal family flexibility, food insecurity was associated with low levels of AI and MFG rsFC. Conditional indirect analysis suggests that the links among food insecurity, rsFC, and impulsive behavior depend on family flexibility. Research Highlights: Adolescent food insecurity was associated with anterior insula and middle frontal gyrus connectivity only at certain levels of family flexibility.High family flexibility attenuated the link between food insecurity and neural connectivity, while low levels of family flexibility increased this risk.High left anterior insula and left middle frontal gyrus connectivity was associated with increased impulsivity 1 year later. [ABSTRACT FROM AUTHOR]

Scapula shape is highly variable across humans and appears to be sexually dimorphic—differing significantly between biological males and females. However, previous investigations of sexual dimorphism in scapula shape have not considered the effects of allometry (the relationship between size and shape). Disentangling allometry from sexual dimorphism is necessary because apparent sex‐based differences in shape could be due to inherent differences in body size. This study aimed to investigate sexual dimorphism in scapula shape and examine the role of allometry in sex‐based variation. We used three‐dimensional geometric morphometrics with Procrustes ANOVA to quantify scapula shape variation associated with sex and size in 125 scapulae. Scapula shape significantly differed between males and females, and males tended to have larger scapulae than females for the same body height. We found that males and females exhibited distinct allometric relationships, and sexually dimorphic shape changes did not align with male‐ or female‐specific allometry. A secondary test revealed that sexual dimorphism in scapula shape persisted between males and females of similar body heights. Overall, our findings indicate that there are sex‐based differences in scapula shape that cannot be attributed to size‐shape relationships. Our results shed light on the potential role of sexual selection in human shoulder evolution, present new hypotheses for biomechanical differences in shoulder function between sexes, and identify relevant traits for improving sex classification accuracy in forensic analyses. [ABSTRACT FROM AUTHOR]

Understanding what facilitates and hinders water drinking is crucial to inform interventions for preventing underhydration. Using the Situated Assessment Method2, we extended previous research by examining what influences water drinking in daily life. We studied 213 UK adults, assessing 13 potential predictors (e.g. thirst, availability of other drinks) of their typical water intake across 10 everyday situations (e.g. during work, dinner). Participants then reported their actual water intake in these situations over three alternating days during a 1‐week follow‐up. We evaluated the variability of water intake and its influences across individuals and situations and the prospective relationship between these influences and water intake. The 13 identified predictors explained substantial proportions of variation in water intake. Factors like habitualness (e.g. subjective effort), self‐relevance (e.g. health consciousness) and immediate feedback (e.g. taste) were positively associated with water intake. However, the influence of these factors varied significantly across individuals and situations. Our results suggest that various interrelated predictors facilitate and hinder water drinking behaviour, emphasising the importance of using comprehensive behaviour theories to inform research in this domain. They also align with growing evidence that reward may regulate habitual behaviour. [ABSTRACT FROM AUTHOR]

Purpose: The oncology quality, characterization, and assessment of real‐world data (Oncology QCARD) Initiative was formed to develop a set of minimum study design and data elements needed to evaluate the fitness of the real‐world data (RWD) source(s) proposed in an initial study concept as part of early interaction with scientific reviewers. Methods: A multidisciplinary executive committee (EC) was established to guide the Oncology QCARD Initiative. The EC conducted a landscape review of published literature, guidances, and guidelines to evaluate relevant dimensions of data quality measurement. Guided by the review and informed by expert feedback, the Oncology QCARD Initial Protocol Characterization (IPC) provides a summary of minimum elements needed to adequately describe an initial clinical study concept that involves RWD and is intended to support decision‐making. Results: Fit‐for‐use data and fit‐for‐purpose design emerged as themes from the landscape analysis. Data that are fit‐for‐use are both relevant (sufficiently capturing exposure, outcomes, and covariates) and reliable (understanding data accrual and quality control and whether the data represent the underlying concepts they are intended to represent) to answer a specific research question. A fit‐for‐purpose design takes appropriate steps to ensure internal and external validity and allows for transparency in reporting. The QCARD‐IPC focuses on high‐level characteristics of RWD sources and study design domains including data temporality, population, medical product exposure, comparators, and covariates, endpoints, statistical analysis, and data quality assurance plans. Conclusions: Evaluation of studies including RWD requires understanding the data source, study design, and potential biases to preliminarily evaluate whether selected RWD are fit‐for‐use for the research question. The Oncology QCARD‐IPC provides a structured, transparent approach to facilitate early review and enhanced communication between study sponsors and scientific reviewers of initial study proposals including RWD. [ABSTRACT FROM AUTHOR]

Background: Paediatric vitreoretinal pathology is distinct from adult cases in both presentation and surgical planning. Here we aim to report the aetiology and epidemiology in children 0–18 years requiring vitreoretinal surgery at a major tertiary paediatric hospital in Queensland, Australia. Methods: Retrospective review of cases requiring vitreoretinal surgery between May 2015 and October 2022 was conducted. Demographics, ocular and medical history, surgical pathology, procedures performed, and epidemiology data were retrieved. Patients were grouped into three main aetiologies: traumatic, syndromic, or secondary. Results: A total of 124 patients, the majority male (87, 70.2%) with a mean age of 10.3 years underwent vitreoretinal surgery. Trauma accounted for 32.3% of cases requiring surgery of which 47% were due to a penetrating eye injury. 35.5% were associated with a syndromic cause with common aetiology including coats, congenital cataract, sticklers, and retinopathy of prematurity. 32.3% developed secondary pathology and retinal detachment was the primary cause for surgery (55%). The average time from symptom onset to presentation was 30 days (SD 56.88) with patients living an average of 306.2 km (SD 558.9) away from the Queensland Children's Hospital. Older age was significantly associated with increased days to presentation in the traumatic group (p < 0.05). Conclusions: This study provides an insight into the aetiology and epidemiology of paediatric vitreoretinal presentations in Queensland, Australia. [ABSTRACT FROM AUTHOR]

Patients with congenital heart disease are living longer due to improved medical and surgical care. Congenital heart disease encompasses a wide spectrum of defects with varying pathophysiology and unique anesthetic challenges. These patients often present for noncardiac surgery before or after surgical repair and are at increased risk for perioperative morbidity and mortality. Although there is no singular safe anesthetic technique, identifying potential error traps and tailoring perioperative management may help reduce morbidity and mortality. In this article, we discuss five error traps based on the collective experience of the authors. These error traps can occur when providing perioperative care to patients with congenital heart disease for noncardiac surgery and we present potential solutions to help avoid adverse outcomes. [ABSTRACT FROM AUTHOR]

Motivational research identifies utility value, or the importance of a learning task to future goals, as central to motivation to learn. This study analyzed survey data (N = 86) collected from adult literacy learners to examine their utility value of writing improvement in grammar and spelling skills, word processing skills, and planning, drafting, and revising skills. Findings revealed that participants had a high utility value of improving writing in all three skill areas and possessed a variety of underlying motivations, including obtaining further education, seeking future employment, and personal reasons. Participants' age, educational attainment, and reading levels showed relationships with utility value of improving grammar and spelling skills, and age showed an additional relationship to utility value of improving word processing skills. This work extends research on motivation in this population and supports the application of expectancy‐value theory to both adult motivation and writing motivation. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the factorial invariance of the factor structure of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC‐V) across the UK, US and Australia & New Zealand (A&NZ). The factorial equivalence of cognitive assessments should be demonstrated before assuming cross‐culture generalizability and interpretations of score comparisons. Methods: Data were obtained from the UK, US and A&NZ normative standardizations of the WISC‐V. The samples consisted of 415 UK, 2200 US and 528 A&NZ children, aged 6–16. Confirmatory factor analysis was applied separately in each sample to establish the baseline model. Next, tests of factorial invariance were undertaken using the recommended hierarchical approach, firstly across the UK and A&NZ samples and then across the UK and US samples. Results: The five‐factor first‐order scoring model was found to be excellent fit across all three samples independently. Strict factorial invariance of the WISC‐V was demonstrated firstly across the UK and A&NZ and secondly the UK and US nationally representative standardization samples. Comparison of latent means found small but significant differences in female children across the UK and A&NZ samples. Conclusions: Consistent with previous research, these results demonstrate the generality of the WISC‐V factor structure across the UK, US and A&NZ. Furthermore, as the WISC‐V factor structure aligns with the Cattell–Horn–Carroll (CHC) model of cognitive abilities, the results add further support to the cross‐cultural generalizability of the CHC model. Small but significant differences in latent factor scores found across samples support the development and use of local normative data. [ABSTRACT FROM AUTHOR]

The air quality index (AQI) is a commonly employed metric for evaluating air quality across diverse locations and temporal spans. Similar to other environmental datasets, AQI data can exhibit outliers data points markedly divergent from the norm, signifying instances of exceptionally favorable or adverse air quality. This becomes crucial in identifying and comprehending severe pollution episodes with far‐reaching environmental and public health implications. This study utilizes air quality data from January 1, 2014, to January 31, 2021, collected at daily intervals in Shanghai City, China, as the experimental dataset. The dataset includes daily AQI measurements, along with six pollutant concentrations: particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). Each pollutant's concentration is measured in micrograms per cubic meter (μ$$ \upmu $$g/m 3$$ {}^3 $$). The dataset is then preprocessed by cleaning and normalizing it before using K‐means clustering to discover different patterns. A stacked ensemble machine learning model that incorporates K‐means clustering, random forest (RF) and gradient boosting classifier (GBC) is developed and compared to decision tree, support vector machine, K‐nearest neighbor and Naive Bayes algorithms to evaluate its performance in identifying outliers using accuracy, precision, recall, and F1‐score. The stacked model outperformed all other established models based on the accuracy, precision, recall, and F1‐score of 0.99, 0.99, 0.97, and 0.99, respectively. [ABSTRACT FROM AUTHOR]

Flexor tendon injury is a common hand trauma that requires surgical repair. The objective was to compare the repaired strength and gliding resistance with a varied number of repair strands and of square knots using a two‐strand‐overhand locking (TSOL) knot. First, isolated suture loops with different number of suture strands and number of closing knots were compared in mechanical strength and failure mode. Then, 90 flexor digitorum profundus (FDP) tendons from turkey digits were used for the tendon repair experiment. Both phases followed a similar 3 × 3 matrix comparing the knot type including TSOL+1SK (square knot), TSOL+2SK, and TSOL+3 SK and repair techniques including two‐, four‐, and six‐strand repairs techniques respectively. The repaired tendons were tested for tendon resistance against pulley (friction), maximum force, force at 2 mm displacement, stiffness, and failure mode. Increasing the number of strands and closing square knots increases the tensile strength and stiffness of flexor tendon repairs and isolated suture loops without a significant effect on tendon friction. An increase in the number of square knots have shown increased strength only in Pennington repair, which correlated with the increased number of knot unraveling, a weak knot failure model. Our data demonstrated that increasing the number of strands is effective for improving the overall strength of tendon repair. When a two‐strand repair is chosen, increasing knot number can improve repair strength. However, the number of knots appears not affecting repair strength in six‐strand repair technique. [ABSTRACT FROM AUTHOR]

(R,S)‐Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)‐Hydroxynorketamine (RR‐HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. To enable future assessments in selected human indications, we report the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RR‐HNK in a Phase 1 study in healthy volunteers (NCT04711005). A six‐level single‐ascending dose (SAD) (0.1–4 mg/kg) and a two‐level multiple ascending dose (MAD) (1 and 2 mg/kg) study was performed using a 40‐minute IV administration emulating the common practice for ketamine administration for depression. Safety assessments showed RR‐HNK possessed a minimal adverse event profile and no serious adverse events at all doses examined. Evaluations of dissociation and sedation demonstrated that RR‐HNK did not possess anesthetic or dissociative characteristics in the doses examined. RR‐HNK PK parameters were measured in both the SAD and MAD studies and exhibited dose‐proportional increases in exposure. Quantitative electroencephalography (EEG) measurements collected as a PD parameter based on preclinical findings and ketamine's established effect on gamma‐power oscillations demonstrated increases of gamma power in some participants at the lower/mid‐range doses examined. Cerebrospinal fluid examination confirmed RR‐HNK exposure within the central nervous system (CNS). Collectively, these data demonstrate RR‐HNK is well tolerated with an acceptable PK profile and promising PD outcomes to support the progression into Phase 2. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusion Implications To assess the feasibility of implementing a culturally responsive version of Gottman's Seven Principles relationship education program in a community‐based setting for married Arab American adults.To provide high‐quality couple and relationship education, it is necessary to acknowledge the population's needs and cultural backgrounds. One ethnic minority group that needs special attention is the Arab American community, which shares protective factors in terms of family support, religious beliefs, resiliency, and collectivist culture.We adapted Gottman's Seven Principles Program and conducted a qualitative feasibility study to examine recruitment capability, program acceptability, demand, and participant response among 16 Arab American married adults.The results emphasize the vital role that thoughtful cultural and linguistic program adaptation played in increasing the acceptability and engagement of Arab American participants. However, results identified the ongoing stigma in Arab American communities against overtly seeking help for marital issues.This feasibility study provides helpful methodological and practical guidance to inform the design of larger scale randomized trials examining the efficacy of culturally responsive marriage education programs.This study outlined actionable strategies, adaptations, venues, and communication channels to reduce barriers and optimize the delivery of marriage education to Arab American couples and families. [ABSTRACT FROM AUTHOR]

Post‐traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring‐loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain‐dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early‐stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open‐label, multicenter, Phase 1b, dose‐finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).Patients with relapsing or primary progressive multiple sclerosis (aged 18–65 years; Expanded Disability Status Scale score 0.0–6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration–time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose‐continuation phase.Eighty‐eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data.Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option. [ABSTRACT FROM AUTHOR]

Electronic cigarette use among adolescents is a growing concern, not only due to the high incidence of co‐use with other substances, such as alcohol, but also due to the fact brain is still maturing during this period. Combined exposure to alcohol and nicotine leads to plastic adaptation of crucial circuits in the brain, which can contribute to the development of addiction. It is well established that nicotine exposure can facilitate alcohol binge drinking, and vice‐versa, in a sex‐, age‐ and exposure‐dependent manner. Nonetheless, the central mechanisms underlying the synergistic relationship between these two substances and the emergence of differential behavioural traits dependent on these factors remain underexplored. Preclinical studies continue to provide valuable insights into such mechanisms. Here, we discuss recent preclinical findings that report behavioural changes characteristic of addiction following nicotine consumption, primarily in models of vaping and alcohol use; and insights into the neural mechanisms impacted by intake of these two substances, with a focus on the adolescent brain. [ABSTRACT FROM AUTHOR]

The pursuit of carbon‐neutral energy has intensified the interest in green hydrogen production from direct seawater electrolysis, given the scarcity of freshwater resources. While Ni‐based catalysts are known for their robust activity in alkaline water oxidation, their catalytic sites are prone to rapid degradation in the chlorine‐rich environments of seawater, leading to limited operation time. Herein, we report a Ni(OH)2 catalyst interfaced with laser‐ablated LiFePO4 (Ni(OH)2/L‐LFP), derived from spent Li‐ion batteries (LIBs), as an effective and stable electrocatalyst for direct seawater oxidation. Our comprehensive analyses reveal that the PO43− species, formed around L‐LFP, effectively repels Cl− ions during seawater oxidation, mitigating corrosion. Simultaneously, the interface between in situ generated NiOOH and Fe3(PO4)2 enhances OH− adsorption and electron transfer during the oxygen evolution reaction. This synergistic effect leads to a low overpotential of 237 mV to attain a current density of 10 mA cm−2 and remarkable durability, with only a 3.3 % activity loss after 600 h at 100 mA cm−2 in alkaline seawater. Our findings present a viable strategy for repurposing spent LIBs into high‐performance catalysts for sustainable seawater electrolysis, contributing to the advancement of green hydrogen production technologies. [ABSTRACT FROM AUTHOR]

Summary: Phenotypic plasticity describes a genotype's ability to produce different phenotypes in response to different environments. Breeding crops that exhibit appropriate levels of plasticity for future climates will be crucial to meeting global demand, but knowledge of the critical environmental factors is limited to a handful of well‐studied major crops.Using 727 maize (Zea mays L.) hybrids phenotyped for grain yield in 45 environments, we investigated the ability of a genetic algorithm and two other methods to identify environmental determinants of grain yield from a large set of candidate environmental variables constructed using minimal assumptions.The genetic algorithm identified pre‐ and postanthesis maximum temperature, mid‐season solar radiation, and whole season net evapotranspiration as the four most important variables from a candidate set of 9150. Importantly, these four variables are supported by previous literature. After calculating reaction norms for each environmental variable, candidate genes were identified and gene annotations investigated to demonstrate how this method can generate insights into phenotypic plasticity.The genetic algorithm successfully identified known environmental determinants of hybrid maize grain yield. This demonstrates that the methodology could be applied to other less well‐studied phenotypes and crops to improve understanding of phenotypic plasticity and facilitate breeding crops for future climates. [ABSTRACT FROM AUTHOR]

Aims: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. Methods and results: Two separate non‐overlapping cohorts were identified: a 419‐patient post‐radical prostatectomy cohort with long term clinical follow‐up and a 209‐patient post‐radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re‐reviewed for high‐risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord‐like growth. For the outcome cohort, Kaplan–Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post‐prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post‐prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. Conclusions: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post‐prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation. [ABSTRACT FROM AUTHOR]

The environmental effects of airborne micro‐ and nano‐size plastic particles are poorly understood. Microscopy and chemical analyses of atmospherically deposited particles on snow surfaces at high elevation (2,865–3,690 m) in the Upper Colorado River basin (UCRB; Colorado Rocky Mountains) revealed the presence of black substances intimately associated with microplastic fibers, particles interpreted to have originated as tire matter. Identical and similar particles occur in shredded tires and road‐surface samples. The substance responsible for the black color of all tires is carbon black, a graphitic light‐absorbing tire additive produced by hydrocarbon combustion that homogeneously permeates the mixture of tire polymers and other additives. Such black tire matter may thus exert radiative effects closely similar to those of black carbon. The presence in snow of many organic compound types common to tires, measured by two‐dimensional gas chromatography, suggests that atmospherically deposited black road‐tire‐wear matter is among the light‐absorbing particulates that advance the onset and rate of snow melt in the UCRB. The mass of road‐tire‐wear particles shed from vehicles may be estimated by multiplying measured amounts of eroded tire‐per‐distance traveled by vehicular distances. Under a combination of measurements and assumptions about the amounts and radiative properties of atmospheric tire‐wear particles, the radiative effects of these particles might add about 10%–30% to those effects from black carbon, an estimate ripe for revision. On regional and global scales, the amounts and effects of emitted and deposited tire‐wear matter likely vary by factors of geographic source, transport pathway, and depositional setting. Plain Language Summary: A major source for airborne microplastic particles is road‐tire wear. Microscopy and chemical analyses of wind‐blown particles on dirty, high‐elevation (2,865–3,690 m) snow surfaces in the Colorado Rocky Mountains revealed the presence of black substances intimately mixed with microplastics, particles interpreted as tire matter. Identical and similar particles occur in shredded tires and in samples collected from road surfaces. The black substance responsible for the black color of all tire particles is carbon black that homogeneously permeates the mixture of tire polymers and other additives. The mass of particles produced by road‐tire wear may be estimated by multiplying measured amounts of eroded tire‐per‐distance traveled by vehicular travel distances. Under assumptions of amounts of tire‐wear matter emitted to the atmosphere, their presence as light‐absorbing particles likely contribute to melting of snow and ice as well as to warming the atmosphere. Key Points: Light absorbing particles, as blackened microplastic matter from road‐tire wear, occur in snow of the Colorado Rocky Mountains (2013–2021)The mass of road‐tire‐wear particles annually generated is estimated to be 6,550 kt, of which about 655–1,965 kt might become airborneThe results are relevant to radiation modeling of snow and ice surfaces as well as the atmosphere [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion There is an increasing research focus on the role of machine learning in the haematology laboratory, particularly in blood cell morphologic assessment. Human‐level performance is an important baseline and goal for machine learning. This study aims to assess the interobserver variability and human‐level performance in blood cell morphologic assessment.A dataset of 1000 single white blood cell images were independently labelled by 10 doctors and morphology scientists. Interobserver variability was calculated using Fleiss' kappa. Observers' labels were then separated into consensus labels used to determine ground truth, and performance labels used to assess observer performance. A machine learning model was trained and assessed using the same cell images. Explainability images (XRAI and IG) were generated for each of the test images.The Fleiss kappa for all 10 observers was 0.608, indicating substantial agreement between observers. The accuracy of human observers was 95%, with sensitivity 72% and specificity 97%. The accuracy of the machine learning model was 95%, with sensitivity 71% and specificity 97%. The model shared similar performance across labels when compared to humans. Explainability metrics demonstrated that the machine learning model was able to differentiate between the cytoplasm and nucleus of the cells, and used these features to perform predictions.The substantial, though not perfect, agreement between human observers highlights the inherent subjectivity in white blood cell morphologic assessment. A machine learning model performed similarly to human observers in single white blood cell identification. Further research is needed to compare human‐level and machine learning performance in ways that more closely reflect the typical process of morphologic assessment. [ABSTRACT FROM AUTHOR]

Objective: The eating disorders field has been limited by a predominant focus on White, Western women, and there is growing recognition of the need to understand cross‐cultural variation in key constructs (i.e., ideal body types). A transdisciplinary, cultural models approach systematizes the incorporation of an "emic" perspective (a culture's own understandings of phenomena) into assessments of relationships between body shapes and eating disorders. Method: Eighty‐one young South Korean men aged 19–34 years living in Seoul participated in this research. A cultural model of body fatness was identified using cultural consensus analysis during 18 months of ethnographic, mixed‐methods fieldwork. Participants also completed questionnaires assessing age, height, weight, sexual identity, university prestige, body dissatisfaction, eating disorder symptoms, and cultural consonance with the Korean cultural model of the ideal male body. Variation in these factors was analyzed using a series of chi‐squares and analyses of variance with the culturally defined categories of body fatness as the independent variables. Results: Cultural consensus analysis found that young South Korean men are consistent in identifying categories of "too thin," "balanced," and "too fat." The "balanced" category contained the lowest proportion of high‐prestige university attendees and the highest average cultural consonance. The "too fat" category was characterized by the highest levels of body dissatisfaction and dieting, as well as proportion of probable eating disorders. Discussion: A cultural models approach identified culturally important factors and patterns in disordered eating among young South Korean men and may be effective for understanding eating disorders in other populations not typically studied. Public Significance: This study applies a systematic, "emic" perspective to young South Korean men's body ideals. Young Korean men share a cultural model of body fatness, and this model frames how they experience risk for eating disorders. This study demonstrates a method for incorporating culture into research on eating disorder risk. [ABSTRACT FROM AUTHOR]

Apex predators are vulnerable to environmental changes which can cascade through trophic levels of an ecosystem. Investigating prey‐predator relationships is important for directing conservation efforts and understanding how species may respond to ecosystem changes. This case study examined the diet and breeding success of the threatened powerful owl Ninox strenua in central Victoria where the box‐ironbark forests have undergone widespread clearing, fragmentation, and degradation. The powerful owl preys predominantly on arboreal mammals, however, some birds are also consumed. By analysing the contents of regurgitated owl pellets of two owl pairs, we found that birds comprised 29.3% of all prey items and contributed the largest proportion of prey biomass for one pair (34.4%). All mammalian prey species identified in the pellet remains are dependent on tree hollows, which are now a scarce and competitive resource in box‐ironbark forests. Despite consuming a diet lower in mammalian prey than found in other studies, breeding success over five consecutive years was 1.4 chicks fledged per pair per year, which is notably higher than historical observations in the region and similar to powerful owls in other parts of their distribution. Our observations suggest that flexibility in prey selection enables powerful owls to occupy ranges that have undergone significant ecosystem change. [ABSTRACT FROM AUTHOR]

Aims: Spinal muscular atrophy (SMA) is a life‐limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success. As opportunities to study treatment‐naïve tissue decrease, we have characterised spinal cord pathology in severe infantile SMA using gold‐standard techniques, providing a baseline to measure treatment success and therapeutic limitations. Methods: Detailed histological analysis, stereology and transmission electron microscopy were applied to post‐mortem spinal cord from severe infantile SMA patients to estimate neuron number at the end of life; characterise the morphology of ventral horn, lateral horn and Clarke's column neuron populations; assess cross‐sectional spinal cord area; and observe myelinated white matter tracts in the clinically relevant thoracic spinal cord. Results: Ventral horn neuron loss was substantial in all patients, even the youngest cases. The remaining ventral horn neurons were small with abnormal, occasionally chromatolytic morphology, indicating cellular damage. In addition to ventral horn pathology, Clarke's column sensory–associated neurons displayed morphological features of cellular injury, in contrast to the preserved sympathetic lateral horn neurons. Cellular changes were associated with aberrant development of grey and white matter structures that affected the overall dimensions of the spinal cord. Conclusions: We provide robust quantification of the neuronal deficit found at the end of life in SMA spinal cord. We question long‐accepted dogmas of SMA pathogenesis and shed new light on SMA neuropathology out with the ventral horn, which must be considered in future therapeutic design. [ABSTRACT FROM AUTHOR]

Dissociative amnesia is a diagnosis category that implies a proposed mechanism (often called dissociation) by which amnesia is caused by psychogenic means, such as trauma, and that amnesia is reversible later. Dissociative amnesia is listed in some of the most influential diagnostic manuals. Authors have noted the similarities in definition to repressed memories. Dissociative amnesia is a disputed category and phenomenon, and here I discuss the plausibility that this cognitive mechanism evolved. I discuss some general conditions by which cognitive functions will evolve, that is, the relatively continuous adaptive pressure by which a cognitive ability would clearly be adaptive if variation produced it. I discuss how adaptive gene mutations typically spread from one individual to the whole species. The article also discusses a few hypothetical scenarios and several types of trauma, to examine the likely adaptive benefits of blocking out memories of trauma, or not. I conclude that it is unlikely that dissociative amnesia evolved, and invite further development of these ideas and scenarios by others. Dissociative amnesia is a presumed memory phenomenon involving the storage of traumatic experiences, followed by a period of no conscious awareness, with later recall possible. It is also a diagnostic category in the influential Diagnostic and Statistical Manual of Mental Disorders. This current paper questions whether this extraordinary type of memory mechanism could have evolved in humans, by examining several different scenarios. The article is unable to identify a plausible consistent advantage that would have led to dissociative amnesia genes to spread throughout a population. [ABSTRACT FROM AUTHOR]

Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and standardised monitoring strategies, there is no consensus among clinicians regarding the relevance of various biochemical markers used in practice, leading to wide variability in their application and interpretation. In this review, we summarise the published evidence on biochemical monitoring of CAH. We discuss temporal variations of the most commonly measured biomarkers throughout the day, the interrelationship between different biomarkers, as well as their relationship with different glucocorticoid and mineralocorticoid treatment regimens and clinical outcomes. Our review highlights significant heterogeneity across studies in both aims and methodology. However, we identified key messages for the management of patients with CAH. The approach to hormone replacement therapy should be individualised, based on the individual hormonal profile throughout the day in relation to medication. There are limitations to using 17‐hydroxyprogesterone, androstenedione and testosterone, and the role of additional biomarkers such 11‐oxygenated androgens which are more disease specific should be further established. Noninvasive monitoring via salivary and urinary steroid measurements is becoming increasingly available and should be considered, especially in the management of children with CAH. Additionally, this review indicates the need for large scale longitudinal studies analysing the interrelation between different monitoring strategies used in clinical practice and health outcomes in children and adults with CAH. [ABSTRACT FROM AUTHOR]

Objectives: Experiencing physical sibling abuse is a form of family violence that is common but understudied. While it is often perceived as a normative aspect of sibling relationships, there are apparent behavioral consequences. The current study aims to advance the literature by utilizing the displaced aggression model and I3 theory to longitudinally examine trait anger as a pathway linking physical sibling abuse to bullying perpetration. Methods: Using data from the Bullying, Sexual, and Dating Violence Trajectories from Early to Late Adolescence in the Midwestern United States, 2008–2013, adolescents (n = 851, M = 14.8 years) completed questionnaires at baseline and were reassessed 6 months later. Results: Results suggested that when adolescents experience physical sibling abuse, they are more likely to engage in bullying perpetration. Mediation analyses indicated that as adolescents were physically abused by a sibling at home, they were more likely to report higher levels of trait anger, which subsequently increased their risk of engaging in bullying perpetration. Conclusion: These results suggest that experiencing physical sibling abuse has long‐term detrimental consequences, including elicitation of trait anger, subsequently predicting bullying perpetration. [ABSTRACT FROM AUTHOR]

This review describes some processes for converting plantain pulp into flour and semolina and the influences that operating conditions can have on some of the technological characteristics (functional and pasting) of this flour. Some traditional African dishes that can be prepared with plantain flour are also presented. A literature review was conducted using a list of keywords and expressions on platforms such as Google, Google Scholar, and ResearchGate. The results show that work carried out to date has mainly focused on a few well known traditional bakery products such as bread, cakes, and biscuits. There has been relatively little research on transforming plantain pulp into flour as part of the preparation of traditional African dishes such as foutou or amala. This work has often been carried out in the laboratory, without any link to local artisanal processes or knowledge of consumer preferences. There is a need to standardize local culinary practices for processing plantain into flour or semolina. The data from this review opens the door for applied research into innovative technological procedures for processing plantain to add value to local dishes adapted to new urban lifestyles, to meet local consumer needs, and to reduce post‐harvest losses. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

We study the impact of an information shock created by an outbreak of lung injuries apparently related to e‐cigarettes. We use data from multiple sources: surveys of risk perceptions conducted before, during, and after the outbreak; an in‐depth survey on risk perceptions and vaping and smoking behavior; and national aggregate time‐series sales data. We find that after the outbreak, consumer perceptions of the riskiness of e‐cigarettes sharply increased. From our estimated e‐cigarette demand models, we conclude that the information shock reduced e‐cigarette demand and the use of e‐cigarettes for smoking cessation by about 30 percent. [ABSTRACT FROM AUTHOR]

The impact of the COVID‐19 pandemic on xenophobia in South Africa is little understood. The Behavioural Immune System (BIS) theory would predict that hostility towards immigrants increases during periods of heightened pathogen stress. This BIS‐hypothesis is tested against the relative strength of three other possible drivers of anti‐immigrant sentiment. These included anger at the national lockdown system, intertemporal relative deprivation, and racial transformation ideology. For these tests nationally representative data (N = 2996), gathered during the height of the 'Omicron' wave, were used. Multivariate analysis showed that COVID‐19 exposure was not associated with more negative sentiments towards immigrants. Fear‐based reactions to the Coronavirus were, in fact, correlated with pro‐immigrant attitudes. Intertemporal relative deprivation and transformation orientations were much better predictors of anti‐immigrant sentiment than pathogen stress. These findings raised questions about the applicability of the BIS‐hypothesis in the context of the Coronavirus and suggest new avenues of academic inquiry. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD‐related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF β‐amyloid‐42/40, neurofilament light chain (NfL), and phospho‐tau‐181(p‐tau181)/β‐amyloid‐42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease‐relevant groups that correlate with biopsy data. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. Highlights: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes.Seven proteins correlate with CNS pathology and gene expression changes.Inflammatory and neuronal gene expression changes correlate with YKL‐40 and NPTXR, respectively.CSF metabolomic analysis identifies pathways that correlate with biopsy data.Fatty acid metabolic pathways correlate with β‐amyloid pathology. [ABSTRACT FROM AUTHOR]

Healthcare professionals (HCPs) have vital roles in providing evidence‐based care to promote healthy micronutrient nutrition in early life. Providing such care requires scalable training to strengthen knowledge and confident application of effective behaviour change skills. Among 33 public and private HCPs (primarily dietitians) in South Africa, we evaluated the behaviour change aspects of a technology‐enabled National Qualification Sub‐Framework level 6 programme, Improving Early Nutrition and Health in South Africa ('ImpENSA'). This programme comprises two self‐directed micronutrient and behaviour change knowledge‐based eLearning and one facilitated online practical skills modules to improve maternal and infant micronutrient nutrition. Using assessments, questionnaires and interviews, we collected data at baseline, after module completion and at 3‐month follow‐up after programme completion. Questionnaire and interview data showed major improvements in understanding of and attitudes towards person‐centred behaviour change support immediately following the eLearning module on behaviour change. The assessment pass rate increased from 38% at baseline to 88% postmodule, demonstrating significant knowledge gain in behaviour change support. Intention to change practice towards a person‐centred approach was high and many had already started implementing changes. Three months postprogramme, support was centred around patients' needs. Open relationships with patients, improved patient outcomes and increased job satisfaction were among reported outcomes. Many reported becoming better change facilitators and reflective practitioners. Additional improvements in understanding and attitudes to behaviour change support were evident, reinforced by making changes and experiencing positive outcomes. The findings suggest that technology‐enabled learning can equip HCPs with knowledge and skills to effectively support behaviour change for healthy micronutrient nutrition during pregnancy and infancy. Key messages: After completing behaviour change skills eLearning, participants' attitudes and understanding of nutrition behaviour change support changed from expert to person centred.Participants adopted a person‐centred approach that focussed on patients' needs and implemented it in practice.At 3‐month follow‐up, consultations became more patient‐led, holistic and information given tailored and designed for patients. Participants reportedly became effective change facilitators and better listeners.Participants reported open relationships with patients, improved patient outcomes, increased job satisfaction and reflective practice.Technology‐enabled learning, when designed appropriately, offers a highly accessible and effective training method to support healthcare professionals to adopt person‐centred nutrition support in practice. [ABSTRACT FROM AUTHOR]

We find a significantly positive relationship between the Tier 1 capital ratio and on‐balance‐sheet liquidity creation for Canadian Big Six banks, implying that large banks in Canada can take risk due to risk absorption by using capital to fund illiquid assets. Our results are robust to the 2018 initiation of a domestic stability buffer (DSB) of total risk‐weighted assets for Pillar 2 risks, core deposits financing, non‐deposit funding restrictions, and bank mergers and acquisitions. The positive relation (regulatory capital ratio with liquidity creation) becomes significantly negative during the 2007–9 Global Financial Crisis and COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Data Monitoring Committees (DMCs) are groups of experts that review accumulating data from one or more ongoing clinical studies and advise the Sponsor regarding the continuing safety of study subjects along with the continuing validity and scientific merit of the study. Although DMCs are widely used, considerable variability exists in their conduct. This paper offers recommendations, derived from sessions given at the 2023 Central European Network International Biometric and Statisticians in the Pharmaceutical Industry Conferences' and the authors' experiences. We focus on four topics that are part of the DMC process and where there is unclarity and inconsistency in current practices: (1) Communication with the DMC—We reflect on the importance of effective, proper communication channels between the DMC and relevant stakeholders to foster collaboration and exchange of critical information while retaining study integrity throughout. (2) Open sessions—We discuss the benefits of incorporating open sessions in DMC meetings to enhance transparency, inclusivity, and the consideration of diverse perspectives, as well as pitfalls of open sessions. (3) Access to efficacy data—We highlight the need for appropriate access to efficacy data by DMCs and discuss how to implement this in practice and how to address potential concerns regarding multiplicity. (4) Interactive data displays—We outline the utilization of interactive data displays to facilitate a more intuitive understanding of study results by the DMC. By addressing these topics, we aim to provide comprehensive practical recommendations that bridge the gap between current practices and optimal DMC functionality. [ABSTRACT FROM AUTHOR]

Aims: To develop a clinical risk model to identify individuals at higher risk of developing new‐onset diabetes and who might benefit more from weight loss pharmacotherapy. Materials and Methods: A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new‐onset diabetes. Twenty‐seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new‐onset diabetes. Results: During a median (interquartile range) follow‐up of 2.3 (1.8–2.7) years, new‐onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high‐density lipoprotein). The clinical risk model showed good discrimination (Harrell's C‐indices 0.802, 95% confidence interval [CI] 0.788–0.817 and 0.807, 95% CI 0.788–0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5‐year area under the curve was 81.2 [79.1–83.5]). While hazard ratios for new‐onset diabetes with a weight‐loss therapy were comparable across risk groups (annual risks of <1%, 1%–5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027). Conclusions: The developed clinical risk model effectively predicts new‐onset diabetes, with potential implications for personalized patient care and therapeutic decision making. [ABSTRACT FROM AUTHOR]

Purpose: Peripheral nerve stimulation (PNS) limits the usability of state‐of‐the‐art whole‐body and head‐only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole‐body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. Methods: We designed, constructed, and tested two actively shielded whole‐body Y‐axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS‐optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head‐imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). Results: The PNS‐optimized design YG2 achieved 46% higher average experimental thresholds for a head‐imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (−3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. Conclusion: The PNS‐optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans. [ABSTRACT FROM AUTHOR]