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Abstract Introduction Despite a demonstrated high accuracy and reported successful implementations, radiographer preliminary image evaluation (PIE) has been slow and infrequent in its rollout across Australia. A key barrier reported to hamper radiographer PIE service implementation is lack of adequate time to review radiographs and provide an accurate interpretation. This study sought to conduct a correlational analysis between radiographer imaging workload and PIE service accuracy. Methods A total of 45,373 exams and 1152 PIE comments evenly distributed each month from January 1, 2022, to December 31, 2022, were reviewed. PIE comments were assessed for consistency with the radiologist's report. The imaging workload (average exams completed per hour) was separated into three, eight‐hour ‘shifts’ based on time of imaging. Correlational analysis was performed using linear regression models and assessed for normality using the Shapiro‐Wilks test. Results The study reported no significant linear association between increasing average workload and reduced service accuracy (P = 0.136). It was however noted that when the average workload increased beyond 7 exams/hour, average service accuracy for PIE was always below 85%. Conclusion This study has demonstrated that, although perceived, there is no statistically significant correlation between x‐ray imaging workload and radiographer PIE service accuracy. Consideration of this correlation to be a significant barrier to participation in such a service was not reported at this site.

Objective The objective of this study is to outline the training of peer coaches in the Moving Well intervention, which was designed to reduce anxiety, depression, and pain catastrophizing in patients before and after total knee replacement (TKR). Methods Selected peer coaches had a history of knee osteoarthritis (KOA), a TKR of 12 months or more before training, and were 60 or older. Training was primarily conducted virtually, with a later addition of one in‐person session. Training centered on developing skills in motivational interviewing (MoI), encompassing techniques like open‐ended questions, affirmations, reflective listening, and summarization. It also covered the MoI processes of engagement, focus, evocation, and planning. Coaches were required to discuss at least 90% of session‐specific topics, which were monitored using checklists for each certification, and to complete individual MoI training, which was not graded. The evaluation of peer coach training involved surveys and a focus group. Results Three women and two men, averaging 75 years in age, completed the peer coach training for the Moving Well intervention. An in‐person training session was added to address technology and MoI skill concerns, greatly enhancing their grasp of MoI skills and their ability to guide others through the program effectively. Peer coaches stressed the importance of live feedback, in‐person training, and incorporating personal experiences into the program content during their training. Conclusion To effectively train older adults as peer coaches for the Moving Well intervention, flexibility in learning formats, personalized guidance, peer support, and regular evaluations were essential in building the necessary MoI competencies to guide research participants in the program.

Background Among presenting conditions in pediatric acute care settings, conduct disorder (CD) is a potentially stigmatizing yet common diagnosis in the setting of behavioral dysregulation requiring psychiatric admission. Concerns exist about over‐diagnosis of CD in non‐Hispanic Black children relative to White peers and the potential for the CD diagnosis to obfuscate manifestations of co‐occurring psychiatric conditions. Methods We evaluated the number of manuscripts on CD diagnoses that report race and ethnicity and co‐occurring mental health characteristics (i.e., history of trauma, attention‐deficit hyperactivity disorder [ADHD], or substance use disorders [SUDs]) that are often undertreated in racially minoritized children. Using the keywords “conduct disorder” or “externalizing disorder,” we screened peer‐reviewed articles in PubMed published from January 2013 to November 2023. Results We screened 2791 manuscripts for potential inclusion, of which 136 were original research articles with data on children with CD diagnoses. Thirteen articles contained racial and ethnic data for people with CD diagnoses, with the majority illustrating that Black children were overrepresented among those with CD diagnoses. No studies provided details on how race and ethnicity were ascertained and few mentioned racism as a potential explanation for racial disparities in CD diagnoses. No studies contained data collected after 2016, with three studies using data collected as early as 2001–2002. Across all articles, data on co‐occurring trauma, ADHD, and SUDs were scarce. Conclusions The overwhelming majority of studies on CD diagnoses did not provide comprehensive data on race and ethnicity and co‐occurring psychiatric disorders in children receiving diagnoses of CD.

Abstract Ferroptosis is a form of cell death characterized by a pro‐oxidative cellular milieu and iron‐dependent lipid peroxidation. Ferroptosis has been implicated in various forms of liver injury, in keeping with the major role of the liver in iron metabolism. Limited research has addressed potential differences in ferroptosis mediators with age and sex, especially in an in vivo model. The goal of this investigation was to evaluate hepatic labile iron and mediators of ferroptosis with ageing in both sexes. Because female animals generally display greater antioxidant defences than males, we hypothesized that females would display a phenotype resistant to ferroptosis. Here, we determined iron contents, protein expression of ferroptosis mediators and measures of oxidative injury in liver samples from 12‐ and 24‐month‐old male and female Fischer 344 rats. In comparison to males, the livers of female rats at both ages contained more non‐haem iron, which was associated with greater ferritin heavy chain expression and attenuated expression of transferrin receptor‐1. In female rats, the 24‐month‐old group had higher contents of thiobarbituric acid reactive substances compared with their 12‐month‐old counterparts, yet similar contents of labile iron. These results suggest a disconnect between labile iron contents and oxidative injury with age. Female animals also displayed greater expression of acyl‐CoA synthetase long‐chain family member 4 (ACSL4), a modulator of ferroptosis, and greater abundance of high molecular weight 4‐hydroxnonenal‐modified proteins. These results demonstrate clear differences in iron and ferroptosis mediators between sexes and suggest that female rats of this strain might be more susceptible to ferroptosis.

ABSTRACT In this work, we develop a new analytical turbine induction model that can incorporate complex inflow conditions including cases where the wind velocity and temperature profiles can vary as functions of height. This induction model is derived from the linearized Navier–Stokes and leads to a second‐order ODE that can be solved using a Green's function formulation. The corresponding Green's function for several configurations are found including the infinite domain, semi‐infinite domain with ground plane, and a power law velocity inflow profile. The results of this approach are then compared with simulations of the turbine induction field using the AMR‐Wind CFD solver with a uniformly loaded actuator disk model. These comparisons show that the Green's function approach captures the centerline blockage, three‐dimensional blockage flow field, and streamwise velocity slow down, with very good agreement for lower thrust conditions and at larger distances away from rotor disk. The effects of shear on the turbine blockage were also compared using a power law inflow profile, and we show that this approach matches the CFD predictions for the cases considered.

Abstract Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene‐abeparvovec (OA) at 3.5 weeks of life. They had no treatment‐related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months. Genotyping revealed 0 copies of SMN1 and a single, hybrid SMN2 gene containing the positive genetic modifier c.835‐44A>G. This was associated with full‐length SMN2 blood mRNA expression levels similar to a 2 copy SMA infant. The observed favorable outcomes are likely due to the genetic modifier combined with early drug administration enabled by prematurity.

Abstract Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin‐oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.

Abstract To understand how ectotherms will respond to warming temperatures, we require information on thermal habitat quality at spatial resolutions and extents relevant to the organism. Measuring thermal habitat quality is either limited to small spatial extents, such as with ground‐based 3D operative temperature (Te) replicas, representing the temperature of the animal at equilibrium with its environment, or is based on microclimate derived from physical models that use land cover variables and downscale coarse climate data. We draw on aspects of both these approaches and test the ability of unoccupied aerial vehicle (UAV) data (optical RGB) to predict fine‐scale heterogeneity in sub‐canopy lizard (Anolis bicaorum) Te in tropical forest using random forest models. Anolis bicaorum is an endemic, critically endangered, species, facing significant threats of habitat loss and degradation, and work was conducted as part of a larger project. Our findings indicate that a model incorporating solely air temperature, measured at the centre of the 20 × 20 m plot, and ground‐based leaf area index (LAI) measurements, measured at directly above the 3D replica, predicted Te well. However, a model with air temperature and UAV‐derived canopy metrics performed slightly better with the added advantage of enabling the mapping of Te with continuous spatial extent at high spatial resolutions, across the whole of the UAV orthomosaic, allowing us to capture and map Te across the whole of the survey plot, rather than purely at 3D replica locations. Our work provides a feasible workflow to map sub‐canopy lizard Te in tropical environments at spatial scales relevant to the organism, and across continuous areas. This can be applied to other species and can represent species within the same community that have evolved a similar thermal niche. Such methods will be imperative in risk modelling of such species to anthropogenic land cover and climate change.

Societal Impact Statement Studies that show how empire influenced the development of plant genetics add to the established history of genetics and 20th‐century agricultural science. One approach to broadening this history is to consider the contributions of students studying abroad and their greater careers back home. Research agendas differed between and within institutions, much as they do today. This article explores the postgraduate education of an Indian groundnut breeder. It highlights the structural challenges faced by researchers at agricultural departments who sought promotion through education and examines the consequences for plant breeding and for farmers. Summary Through the biography of V.K. Badami, this article contributes to debates about genetics and plant breeding in the history of science. Badami, an accomplished breeder in the Mysore Department of Agriculture, took a leave to study genetics at the University of Cambridge. His professors nearly failed him, yet Badami's groundnut breeding experiments proved influential for Indian farmers as well as advances in crop science. This history adds to the thesis that academic genetics varied in support of professional plant breeding by comparing institutional expections between Mysore and Cambridge. The argument is developed by reading Badami's student records along with his groundnut breeding experiments in South India. The study connects the disciplinary history of genetics to plant breeding for the British empire. Badami's experience at Cambridge is indicative of the power relationship between academic genetics and imperial plant breeding in the early 20th century. In this case, his commitments as an Indian agricultural officer conflicted with the discipline's devotion to quantitative analysis.

Abstract Human papillomavirus (HPV)‐related cervical and nasopharyngeal cancers differ in molecular mechanisms underlying the oncogenic processes. The disparity may be attributed to differential expression of oncoproteins. The current study investigated the host oncogenes expression pattern in HPV‐associated cervical and nasopharyngeal cancer. Formalin‐fixed paraffin‐embedded tissues originating from the nasopharyngeal and cervical regions were screened using Hematoxylin and Eosin staining. Genomic DNA and total RNA were extracted from confirmed cancer biopsies and non‐cancer tissues (NC). HPV was detected by PCR using MY09/GP5+/6+ primers. Protein expression levels of AKT, IQGAP1, and MMP16 in HPV‐infected cancers and controls were determined by immunohistochemistry. RT‐qPCR was used to profile mRNAs of the oncogenes. AKT and IQGAP1 proteins were highly expressed in the epithelial cancers compared with the non‐cancer tissues (p 0.05). The oncoproteins expression level between the HPV‐positive and HPV‐negative cancer biopsies showed no significant difference (p

Abstract Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) is diagnosed by serum MOG‐immunoglobulin G (MOG‐IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG‐IgG. Only 7/1016 (0.7%) seronegative patients had CSF‐restricted MOG‐IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF‐restricted MOG‐IgG had a low sensitivity (2.63%, 95%CI 0.55–7.50%) and low positive predictive value (1.97%, 95%CI 0.45–8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF‐restricted MOG‐IgG in patients without clinico‐radiological features consistent with MOGAD.

Abstract Aims Hyperactivity of Ca2+/calmodulin‐dependent protein kinase II (CaMKII) has emerged as a central cause of pathologic remodelling in heart failure. It has been suggested that CaMKII‐induced hyperphosphorylation of the ryanodine receptor 2 (RyR2) and consequently increased diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) is a crucial mechanism by which increased CaMKII activity leads to contractile dysfunction. We aim to evaluate the relevance of CaMKII‐dependent RyR2 phosphorylation for CaMKII‐induced heart failure development in vivo. Methods and results We crossbred CaMKIIδC overexpressing [transgenic (TG)] mice with RyR2‐S2814A knock‐in mice that are resistant to CaMKII‐dependent RyR2 phosphorylation. Ca2+‐spark measurements on isolated ventricular myocytes confirmed the severe diastolic SR Ca2+ leak previously reported in CaMKIIδC TG [4.65 ± 0.73 mF/F0 vs. 1.88 ± 0.30 mF/F0 in wild type (WT)]. Crossing in the S2814A mutation completely prevented SR Ca2+‐leak induction in the CaMKIIδC TG, both regarding Ca2+‐spark size and frequency, demonstrating that the CaMKIIδC‐induced SR Ca2+ leak entirely depends on the CaMKII‐specific RyR2‐S2814 phosphorylation. Yet, the RyR2‐S2814A mutation did not affect the massive contractile dysfunction (ejection fraction = 12.17 ± 2.05% vs. 45.15 ± 3.46% in WT), cardiac hypertrophy (heart weight/tibia length = 24.84 ± 3.00 vs. 9.81 ± 0.50 mg/mm in WT), or severe premature mortality (median survival of 12 weeks) associated with cardiac CaMKIIδC overexpression. In the face of a prevented SR Ca2+ leak, the phosphorylation status of other critical CaMKII downstream targets that can drive heart failure, including transcriptional regulator histone deacetylase 4, as well as markers of pathological gene expression including Xirp2, Il6, and Col1a1, was equally increased in hearts from CaMKIIδC TG on a RyR WT and S2814A background. Conclusions S2814 phosphoresistance of RyR2 prevents the CaMKII‐dependent SR Ca2+ leak induction but does not prevent the cardiomyopathic phenotype caused by enhanced CaMKIIδC activity. Our data indicate that additional mechanisms—independent of SR Ca2+ leak—are critical for the maladaptive effects of chronically increased CaMKIIδC activity with respect to heart failure.

Abstract Background Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods This hypothesis‐generating analysis used biospecimens collected from a multi‐centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log‐transformed, and main effects analyses were conducted using linear mixed‐effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Results Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin‐15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (−2.69 pg/mL, 95% CI: −4.31, −1.07; adjusted P = 0.014) and interleukin‐15 (−1.74 pg/mL, 95% CI: −2.79, −0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. Conclusions This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis‐generating observation warrants further basic, translational and clinical investigation and replication.

Abstract Introduction and Objectives Voiding dysfunction remains a common side effect postprostate biopsy leading to significant morbidity. Alpha blockers have emerged as a potential therapeutic option to mitigate this risk, with various centres already incorporating its use in practice. Despite this, the literature regarding its efficacy remains inconclusive. Hence, a systematic review was performed to quantify the effect of perioperative alpha blockers on prostate biopsy‐related voiding function. Methods A systematic search in MEDLINE, Embase and PubMed between January 1989 and July 2023 was performed to identify relevant articles. Two independent reviewers independently screened abstracts, full texts and performed data extraction. Data including International Prostate Symptom Scores (IPSS), voiding flow rates (Qmax), postvoid residuals (PVR), rates of acute urinary retention (AUR) and quality of life (QoL) scores were extracted. Results were combined in an inverse variance random effects meta‐analysis. Results A total 808 patients from six randomised controlled trials (RCTs) comparing alpha blockers to controls were included. All articles excluded patients with pre‐existing voiding dysfunction. Pooled outcomes demonstrated statistically significant differences favouring alpha blocker usage in all objective and subjective measures including IPSS (mean difference 4.21, 95% confidence interval [CI] 2.58–5.84, p

Abstract Optimal nutrition during infancy is critical given its influence on lifelong health and wellbeing. Two novel methods of infant complementary feeding, commercial baby food pouch use and baby‐led weaning (BLW), are becoming increasingly popular worldwide. Household food insecurity may influence complementary feeding practices adopted by families, but no studies have investigated the use of BLW and baby food pouches in families experiencing food insecurity. The First Foods New Zealand study was a multicentre, observational study in infants 7.0–9.9 months of age. Households (n = 604) were classified into one of three categories of food insecurity (severely food insecure, moderately food insecure, and food secure). The use of complementary feeding practices was assessed via a self‐administered questionnaire, both at the current age (mean 8.4 months) and retrospectively at 6 months. Mothers experiencing severe food insecurity had 5.70 times the odds of currently using commercial baby food pouches frequently (≥5 times/week) compared to food secure mothers (95% CI [1.54, 21.01]), reporting that pouches were ‘easy to use’ (89%) and made it ‘easy to get fruits and vegetables in’ (64%). In contrast, no evidence of a difference in the prevalence of current BLW was observed among mothers experiencing moderate food insecurity (adjusted OR; 1.28, 95% CI [0.73, 2.24]) or severe food insecurity (adjusted OR; 1.03, 95% CI [0.44, 2.43]) compared to food secure mothers. The high prevalence of frequent commercial baby food pouch use in food insecure households underscores the need for research to determine whether frequent pouch use impacts infant health.

Abstract Extracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs and other molecular footprints from their cell of origin, and thus have evident applications in liquid biopsy, therapeutics, and intercellular communication. Yet, the complete transcriptomic landscape of EVs is poorly characterized due to critical limitations including variable protocols used for EV‐RNA extraction, quality control, cDNA library preparation, sequencing technologies, and bioinformatic analyses. Consequently, there is a gap in knowledge and the need for a standardized approach in delineating EV‐RNAs. Here, we address these gaps by describing the following points by (1) focusing on the large canopy of the EVs and particles (EVPs), which includes, but not limited to – exosomes and other large and small EVs, lipoproteins, exomeres/supermeres, mitochondrial‐derived vesicles, RNA binding proteins, and cell‐free DNA/RNA/proteins; (2) examining the potential functional roles and biogenesis of EVPs; (3) discussing various transcriptomic methods and technologies used in uncovering the cargoes of EVPs; (4) presenting a comprehensive list of RNA subtypes reported in EVPs; (5) describing different EV‐RNA databases and resources specific to EV‐RNA species; (6) reviewing established bioinformatics pipelines and novel strategies for reproducible EV transcriptomics analyses; (7) emphasizing the significant need for a gold standard approach in identifying EV‐RNAs across studies; (8) and finally, we highlight current challenges, discuss possible solutions, and present recommendations for robust and reproducible analyses of EVP‐associated small RNAs. Overall, we seek to provide clarity on the transcriptomics landscape, sequencing technologies, and bioinformatic analyses of EVP‐RNAs. Detailed portrayal of the current state of EVP transcriptomics will lead to a better understanding of how the RNA cargo of EVPs can be used in modern and targeted diagnostics and therapeutics. For the inclusion of different particles discussed in this article, we use the terms large/small EVs, non‐vesicular extracellular particles (NVEPs), EPs and EVPs as defined in MISEV guidelines by the International Society of Extracellular Vesicles (ISEV).

ABSTRACT Background Obesity is a chronic, relapsing, progressive disease of excess adiposity that increases the risk of dying from at least 16 types of cancer. The prevalence of obesity has increased more rapidly in cancer survivors compared with the general population. Tailored weight management strategies are needed to improve prognosis and health outcomes in the growing population of cancer survivors. However, certain cancer survivor population subgroups require unique consideration when developing weight management strategies. Methods In a symposium convened by The Obesity Society during ObesityWeek 2023 titled “From Surviving to Thriving: Key Considerations for Weight Control Across Diverse Cancer Survivorship Populations,” experts presented the current state of the science and highlighted existing research gaps. Results Topics included key considerations for weight management in adolescent and young adult cancer survivors, older adult cancer survivors, and understudied cancer survivor subgroups at high risk for poor health outcomes and innovative interventions that can be tested to improve cancer survivorship. Conclusions This report reviews the symposium and offers perspectives from the expert panel about unique opportunities for future research on tailored weight management strategies to equitably improve prognosis and health outcomes in the diverse and growing population of cancer survivors.

ABSTRACT We studied a population of large varanid lizards (yellow‐spotted monitors Varanus panoptes) on a floodplain in tropical Australia. Growth records from radio‐tracked lizards show that despite their large adult body sizes (to > 7 kg in males), these lizards attained sexual maturity at less than 1 year of age and rarely lived for more than 2 years (females) or 4 years (males), even before mortality increased due to the arrival of toxic cane toads (Rhinella marina). This is a “faster” life history than has been reported for other species of large monitors. Growth was especially rapid in males during the wet season. The low survivorship prior to toad invasion was due to predation by pythons; communal nesting by female varanids may render them especially vulnerable. The life history of yellow‐spotted monitors requires high feeding rates, favouring the evolution of “risky” tactics such as consuming novel prey items (such as cane toads); and the combination of high abundance (> 20 adult lizards per square kilometre) and high feeding rates (> 9.9 kg of prey per lizard per annum) means that these giant lizards play a critical role in energy and nutrient flow within the floodplain ecosystem. As a result, foodwebs with the yellow‐spotted monitor as an apex predator are more vulnerable to disruption by cane toads than is the case in other parts of the toad's invasive range, where the varanid species affected by toads have “slower” life histories.

Abstract Interpreting the paleomagnetic records of altered rocks, especially those from Earth's earliest history, is complicated by metamorphic overprints and recrystallization of ferromagnetic minerals. However, these records may be as valuable as a primary signal if the timing and mechanism of alteration‐related remagnetizations can be ascertained. We illustrate the success of this approach in the case of seafloor hydrothermal alteration by integrating simple rock magnetic and magnetic microscopy data with petrography, hyperspectral imagery, aeromagnetic surveys, field mapping, and geochronology of Paleoarchean basalts from North Pole Dome located in the East Pilbara Craton, Western Australia. We identify 12 hydrothermal episodes during the deposition of the stratigraphy between ∼3490 and 3350 Ma. These episodes produced stratabound zones of hydrothermal alteration with predictable facies successions of mineral assemblages reflecting sub‐seafloor gradients in fluid temperature, pH, composition, and water/rock ratios. Rock magnetic data and magnetic microscopy pinpoint the secondary ferromagnetic minerals within each alteration assemblage, revealing a specific single‐domain magnetite population within leucoxenes (titanite and anatase after primary titanomagnetites) that always accompanies low‐water/rock alteration in fluids buffered to pH equilibrium with the host basalts. Highly uniform magnetic properties indicate that once formed, these magnetites remain unchanged upon further exposure to rock buffered fluids, stabilizing them against later alteration events and making them durable paleofield recorders. The altered basalts hosting this magnetite have unique and consistent appearances, mineralogy, IR absorption features, aeromagnetic signatures, and magnetic properties across all hydrothermal systems studied here, highlighting how integrating these data sets can identify and interpret this alteration style in future paleomagnetic investigations.

Abstract Venetoclax is a first‐in‐class orally administered B‐cell lymphoma‐2 inhibitor used to treat chronic lymphocytic leukemia (CLL). Venetoclax is primarily metabolized in the liver by cytochrome P450 (CYP) 3A4 to its major metabolite M27, via M5, and M2, M3, and M4 via oxidation. Although venetoclax is a breakthrough in CLL treatment, managing drug safety and toxicity remains a clinical challenge. The objectives of this study were to investigate how individual CYP3A activity and protein expression affect hepatic venetoclax metabolism in vitro and examine whether plasma 4β‐hydroxycholesterol (4β‐HC)/cholesterol ratio can predict venetoclax metabolism in vitro and in vivo. In human liver microsomes (n = 20) and primary human hepatocytes (n = 15), venetoclax metabolite formation varied widely between donors and significantly correlated with CYP3A activity (midazolam 1′‐hydroxylation) and CYP3A4 protein expression. Venetoclax metabolite formation positively correlated with 4β‐HC/cholesterol ratio in plasma samples from the matched non‐infant donors (n = 14, ages 3–63 years). In an observational pilot study of real‐world patients with CLL (n = 12, ages 56–84 years) treated with venetoclax, the plasma M3/venetoclax metabolic ratio negatively correlated with plasma 4β‐HC/cholesterol ratio and positively correlated with patient age. Plasma 4β‐HC/cholesterol ratio negatively correlated with patient age. Differences between the in vitro data, which showed a positive association between venetoclax metabolism, hepatic CYP3A markers, and plasma 4β‐HC/cholesterol ratio, and the in vivo findings in patients with CLL could be due to age or other factors regulating plasma 4β‐HC/cholesterol and/or venetoclax disposition. Future studies with larger sample sizes are needed to investigate age‐related changes in venetoclax metabolism and plasma 4β‐HC/cholesterol ratio.

Abstract Persian walnuts (Juglans regia L.) are the second most produced and consumed tree nut, with over 2.6 million metric tons produced in the 2022–2023 harvest cycle alone. The United States is the second largest producer, accounting for 25% of the total global supply. Nonetheless, producers face an ever‐growing demand in a more uncertain climate landscape, which requires effective and efficient walnut selection and breeding of new cultivars with increased kernel content and easy‐to‐open shells. Past and current efforts select for these traits using hand‐held calipers and eye‐based evaluations. Yet there is plenty of morphology that meets the eye but goes unmeasured, such as the volume of inner air or the convexity of the kernel. Here, we study the shape of walnut fruits based on X‐ray computed tomography three‐dimensional reconstructions. We compute 49 different morphological phenotypes for 1264 individual nuts comprising 149 accessions. These phenotypes are complemented by traits of breeding interest such as ease of kernel removal and kernel‐to‐nut weight ratio. Through allometric relationships, relative growth of one tissue to another, we identify possible biophysical constraints at play during development. We explore multiple correlations between all morphological and commercial traits and identify which morphological traits can explain the most variability of commercial traits. We show that using only volume‐ and thickness‐based traits, especially inner air content, we can successfully encode several of the commercial traits.

ABSTRACT Great Bay Estuary (GBE) is a complex estuarine system at the convergence of seven rivers, ocean and land. The GBE ecosystem supports typical estuarine species but, like many estuaries, has been a target of both invasive and range‐expanding species. The goal of this study was to compare abundance, sex and size distribution of green crabs between oyster farm sites and non‐farmed sites within GBE in 2021 and 2022. Overall catch was higher in 2021 compared to 2022. The highest population of green crabs was estimated to be in the farm area around Cedar Point, and natural/restoration area near Moody Point had the smallest European green crab population. In both years, the majority of green crabs captured (98%) were adult males, and few were juveniles captured. At the last sampling date of 2021 and 2022, most crabs were large (68 ± 0.5 mm and 63 ± 2 mm carapace width, respectively). Shellfish growers, restoration and management teams could use these data in mitigation strategies to sustain industries and enhance GBE health. This information is important for oyster restoration initiatives and oyster growers as they may want to: consider putting traps around their restoration reefs and farms to help reduce green crab infestation/predation in their growing areas; make decisions regarding best management practices and optimal growing locations when applying for permits; and work with management teams with gear improvement, such as floating gear, to reduce green crab intrusion into cages. High‐priority locations for trapping should be areas such as oyster farms, oyster reefs and restoration sites.

Abstract Background Health guideline developers engage with interested people and groups to ensure that guidelines and their recommendations are relevant and useful to those who will be affected by them. These ‘interest‐holders’ include patients, payers/purchasers of health services, payers of health research, peer review editors, product makers, programme managers, policymakers, providers, principal investigators, and the public. The Guidelines International Network (GIN) and McMaster University Guideline Development Checklist describes 146 steps of the guideline process organized into 18 topics. While one topic focuses on engagement, it does not describe how to engage with interest‐holders. In addition, interest‐holder input could be sought throughout the guideline development process. This scoping review is part of a series of four related reviews. The three other reviews address barriers and facilitators to engagement in guideline development, managing conflicts of interest in guideline development, and assessing the impact of interest‐holder engagement on guideline development. The four reviews will inform the development of guidance for multi‐interest‐holder engagement in guideline development; the GIN‐McMaster Guideline Development Checklist Extension for Engagement. Objectives The objective of this scoping review is to identify, describe, and summarise existing guidance and methods for multi‐interest‐holder engagement throughout the health guideline development process. Search Methods We conducted one comprehensive search for studies of engagement in guidelines to meet the inclusion criteria of one or more of the four systematic reviews in this series. We searched MEDLINE (OVID), CINAHL (EBSCO), EMBASE (OVID), PsycInfo (OVID) and SCOPUS databases up to September 2022. We did not include limits for date, study design, or language. We searched websites of agencies and organizations that engage interest‐holder groups, such as the Agency for Healthcare Research and Quality (AHRQ), CIHR Strategy for Patient‐Oriented Research (SPOR), National Institute for Health and Care Research (NIHR) Be Part of Research, Guidelines International Network (G‐I‐N), the National Institute for Health and Care Excellence, and the PatientCentred Outcomes Research Institute (PCORI). We handsearched the websites of guideline producing agencies. We solicited additional grey literature from the members of the MuSE Consortium. Selection Criteria Studies were included in this review if they reported on engagement of any of our identified groups, patients, payers/funders of research, payers/purchasers of health services, policymakers, programme managers, providers, principal investigators/researchers, peer review editors, product makers in the development of a health guideline. Titles and abstracts of identified citations were screened independently, in duplicate. The full text of potentially relevant papers were screened for eligibility into one or more of the four reviews in the series. Screening was done independently, by two reviewers. The team held weekly meetings with all reviewers involved in screening to discuss and resolve conflicts. Data Collection and Analysis Two reviewers extracted relevant data into a pilot‐tested data extraction form using Excel. We used the GIN‐McMaster guideline development checklist as a framework for extracting the available guidance for each of our identified interest‐holder groups throughout the development process. We presented descriptive statistics of the number of papers reporting guidance for each groups across the steps of the guideline process. We synthesized the relevant text using a qualitative meta‐summary approach. Main Results We included 16 papers (from 17 reports). These papers were from Australia, Denmark, the Netherlands, the UK, and the USA, and eight papers were international (countries not specified). The papers provided guidance for at least one of our interest‐holder groups for at least one stage of guideline development. We mapped this guidance to the GIN‐McMaster Guideline Development Checklist to identify the available guidance for each of our interest‐holder groups across all stages of the guideline development process. Guidance was available for patient engagement in 15 of the 16 papers. At least two papers provided guidance for each of the 18 topics of the GIN‐McMaster Guideline Development Checklist. For healthcare providers, 9 papers provided guidance for their engagement across 10 of the 18 guideline development topics. Guidance for engaging with the public was provided for 14 of the 18 topics and reported in 4 of our included papers. For payers/purchasers of health services, policymakers, product makers, programme managers, and principal investigators, 2–3 papers provided guidance for these groups across 4–7 topics of the GIN‐McMaster checklist. We did not identify any specific guidance for payers of health research or for editors of peer‐reviewed journals. Authors' Conclusions Guidance for interst‐holder engagement in guidelines is available but has focused primarily on patients. We will utilize the guidance identified in this scoping review to inform the GIN‐McMaster Guideline Development Checklist Extension for engagement. Combined with the information obtained from the other systematic reviews in this series, we will address the gaps in guidance for the other identified interest‐holder groups.

Abstract Prevention and early detection of invasive species are championed as the most cost‐effective and efficient strategies for reducing or preventing negative impacts on ecosystems. Spotted lanternfly (SLF), Lycorma delicatula, is a recently introduced invasive insect whose range in the United States has been expanding rapidly since it was first discovered in Pennsylvania in 2014. Feeding by this planthopper can cause severe impacts on agricultural production, particularly grapes (Vitis spp.). Human visual surveys are the most common search method employed for detection but can be ineffective due to the insect's cryptic egg masses and low density during early stages of infestation. Therefore, finding alternative early detection methods has become a priority for agencies tasked with addressing SLF management. This study experimentally tested whether trained detector dogs could improve the probability of detecting SLF in both agricultural and forest settings. We surveyed transects in 20 vineyards and their adjacent wooded areas in Pennsylvania and New Jersey, USA, and used a multiscale occupancy model to estimate detection probability achieved by human observers and detection dogs as a function of SLF infestation level, weather, and habitat covariates. We modeled transect‐level occupancy of SLF as a function of infestation level, habitat type, topographic position index, and distance to forests. Occupancy probability of SLF was higher on vines within vineyards than in forests, and occupancy declined with increasing distance from forests, which is informative for future search efforts. Detection probability of SLF was lower at forested sites but was higher at high infestation sites. Detection dogs had a lower detection probability than humans in the vineyards, but the detection probability of dogs was >3× greater than that of humans in forested sites. Our study suggests that detection dogs are more effective than human visual searches as an early detection method for SLF in forested areas, and utilizing detector dogs could strengthen SLF early detection efforts. This study demonstrates the potential applicability of using canine‐assisted search strategies combined with occupancy models to enhance the surveillance and prevention of other difficult‐to‐detect invasive species.

Abstract Constraining past West Antarctic Ice Sheet (WAIS) change helps validate numerical models simulating future ice sheet dynamics. Following rapid deglaciation during the mid‐Holocene, ice near Thwaites Glacier was ∼35 m thinner than present; however, the timing of ice regrowth to its present configuration remains unknown. To fill this knowledge gap, we present cosmogenic nuclide exposure ages of cobbles from the surface of a moraine situated between Thwaites and Pope glaciers. We infer that the moraine formed and stabilized in the Late Holocene (∼1.4 ka) when a small glacier thickened. We also present a novel reconstruction of WAIS volume constrained by sea‐level data, which demonstrates that moraine formation coincided with a large‐scale WAIS readvance. Our new geologic constraints will help inform models of the solid Earth response to surface mass loading, improving our understanding of ice sheet dynamics in a vulnerable part of WAIS.

Abstract In patients with out‐of‐hospital cardiac arrest (OHCA) who attain return of spontaneous circulation (ROSC), rearrest while in the prehospital setting represents a significant barrier to survival. To date, there are limited data to guide prehospital emergency medical services (EMS) management immediately following successful resuscitation resulting in ROSC and prior to handoff in the emergency department. Post‐ROSC care encompasses a multifaceted approach including hemodynamic optimization, airway management, oxygenation, and ventilation. We sought to develop an evidenced‐based, goal‐directed bundle of care targeting specified vital parameters in the immediate post‐ROSC period, with the goal of decreasing the incidence of rearrest and improving survival outcomes. Here, we describe the rationale and development of this goal‐directed bundle of care, which will be adopted by several EMS agencies within California. We convened a group of EMS experts, including EMS Medical Directors, quality improvement officers, data managers, educators, EMS clinicians, emergency medicine clinicians, and resuscitation researchers to develop a goal‐directed bundle of care to be applied in the field during the period immediately following ROSC. This care bundle includes guidance for prehospital personnel on recognition of impending rearrest, hemodynamic optimization, ventilatory strategies, airway management, and diagnosis of underlying causes prior to the initiation of transport.

Background Although sex differences in coronary artery disease (CAD) risk have been observed, little is known about the role of sex hormones in CAD genetics. Accounting for sex hormone levels may help identify CAD‐risk loci and extend our knowledge of its genetic architecture. Methods and Results A total of 365 662 individuals of European ancestry enrolled in the UK Biobank were considered. Genetic interaction of total testosterone, bioavailable testosterone, and SHBG (sex hormone‐binding globulin) were evaluated. Gene–environment interactions in millions of samples software was used to conduct sex‐stratified genome‐wide interaction analysis with prevalent CAD as the outcome. Participant age at enrollment and principal components 1 to 10 were adjusted as covariates. We identified 45 loci in men and 8 loci in women that reached genome‐wide significance (P

Background Abdominal aortic aneurysms (AAAs) are focal dilatations of the abdominal aorta that expand progressively, increasing their risk of rupture. Rupture of an AAA is associated with high mortality rates, but the mechanisms underlying the initiation, expansion, and rupture of AAAs are not yet fully understood. We aimed to characterize the pathophysiology of AAAs and identify new genes associated with AAA initiation and progression. Methods and Results This study used RNA sequencing data on 140 samples, becoming the largest RNA sequencing data set for differential expression studies of AAAs. We performed differential expression analyses and analyses of differential splicing between dilated and nondilated aortic tissue samples, and between AAAs of different diameters. We identified 3002 differentially expressed genes between AAAs and controls that were independent of ischemic time, 1425 of which were new. Additionally, 8 genes (EXTL3, ZFR, DUSP8, DISP1, USP33, VPS37C, ZNF784, RFX1) were differentially expressed between AAAs of varying diameters and between AAAs and control samples. Finally, 7 genes (SPP1, FHL1, GNAS, MORF4L2, HMGN1, ARL1, RNASE4) with differential splicing patterns were also differentially expressed genes between AAAs and controls, suggesting that splicing differences in these genes may contribute to the observed expression changes and disease development. Conclusions This study identifies new genes and splicing patterns associated with AAAs and validates previous relevant pathways on AAAs. These findings contribute to the understanding of the complex mechanisms underlying AAAs and may provide potential targets to limit AAA progression and mortality risk.

Abstract One third of epilepsy patients are resistant to treatment with current anti‐seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2‐deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Abstract This strategic plan summarizes the major accomplishments achieved in the last quinquennial by the soybean [Glycine max (L.) Merr.] genetics and genomics research community and outlines key priorities for the next 5 years (2024–2028). This work is the result of deliberations among over 50 soybean researchers during a 2‐day workshop in St Louis, MO, USA, at the end of 2022. The plan is divided into seven traditional areas/disciplines: Breeding, Biotic Interactions, Physiology and Abiotic Stress, Functional Genomics, Biotechnology, Genomic Resources and Datasets, and Computational Resources. One additional section was added, Training the Next Generation of Soybean Researchers, when it was identified as a pressing issue during the workshop. This installment of the soybean genomics strategic plan provides a snapshot of recent progress while looking at future goals that will improve resources and enable innovation among the community of basic and applied soybean researchers. We hope that this work will inform our community and increase support for soybean research.

Abstract The analysis of vascular morphology and functionality enables the assessment of disease activity and therapeutic effects in various pathologies. Raster‐scanning optoacoustic mesoscopy (RSOM) is an imaging modality that enables the visualization of superficial vascular networks in vivo. In murine models of colitis, deep vascular networks in the colon wall can be visualized by transrectal absorber guide raster‐scanning optoacoustic mesoscopy (TAG‐RSOM). In order to accelerate the implementation of this technology in translational studies of inflammatory bowel disease, an image‐processing pipeline for TAG‐RSOM data has been developed. Using optoacoustic data from a murine model of chemically‐induced colitis, different image segmentation methods are compared for visualization and quantification of deep vascular patterns in terms of vascular network length and complexity, blood volume, and vessel diameter. The presented image‐processing pipeline for TAG‐RSOM enables label‐free in vivo assessment of changes in the vascular network in murine colitis with broad applications for inflammatory bowel disease research.

Background HIV‐associated cardiovascular disease (CVD) is increasing in prevalence. The mechanisms underlying the heightened cardiovascular risk faced by people with HIV (PWH), however, remain poorly defined. Recent studies indicate an important role of lipoprotein(a) (Lp[a]) in predicting CVD risk in the general population, but little is known regarding its role in HIV‐associated CVD. Thus, we sought to evaluate whether Lp(a) is elevated in PWH and if it is associated with impaired coronary endothelial function (CEF), a known mediator of CVD in PWH. Methods and Results In this cross‐sectional study, cardiac magnetic resonance imaging with isometric handgrip exercise, an endothelial dependent stressor, was performed to assess CEF in 65 PWH and 52 controls without HIV. Percent changes in coronary cross‐sectional area and coronary blood flow from rest to stress were used to quantify CEF. Lp(a) levels were assessed by immunoturbidimetric assay at the time of magnetic resonance imaging. Lp(a) levels were higher in PWH compared with controls (78 nmol/L [39–137 nmol/L] versus 45.5 nmol/L [18–102.5 nmol/L], P

ABSTRACT Ecosystems in coastal waters of Gulf of Maine (GOM) are undergoing environmental challenges in response to climate change and anthropogenic stressors. eDNA metabarcoding, a powerful tool for assessing the fish community structure, was used to identify fish communities in three types of GOM aquatic environments (sand, macroalgae, and eelgrass) in Maine and New Hampshire, USA. The available 12S rRNA fish universal primer analysis system (MiFish and 12S‐V5) was modified using nested polymerase chain reaction (PCR) to improve targeting of fish products and reduce non‐target products. The nested PCR strategy allowed successful amplification of 12S rRNA genes in fishes without production of non‐target products and identified 28 fish groups at the genus level. Presence/Absence data and Relative Abundance showed significant differences among locales but not among habitats. Myoxocephalus sp. were found at all sampling sites. Relative Abundance data revealed that Menidia menidia and Brevoortia sp. were statistical indicator species in Goosefare, Maine, and New castle, New Hampshire, respectively. Although beta diversity indicated that fish communities were not different across habitats, statistical analysis found that Pholis sp. and Ammodytes sp. were dominant species in macroalgae and sand, respectively. To our knowledge, this is the first metabarcoding study to assess fish communities in the Western Atlantic region using the MiFish primer set, and the study suggests that metabarcoding is useful for mapping geographic and temporal marine fish diversity.

Abstract A focus of sea turtle management has been reducing bycatch in commercial fisheries, but sustainable harvest for consumption is also an important objective in many nations. Identifying how much different fisheries contribute to turtle mortality could help focus limited management resources. We estimated national scale turtle catches for two fisheries in the Solomon Islands: a small‐scale reef fishery where turtles are caught for food and sale, and an offshore longline fishery where turtles are bycatch. The footprint of the longline fishery spanned the entire exclusive economic zone of the Solomon Islands and was 67 times bigger than the footprint of the small‐scale fishery. The median catch summed across both fisheries was ∼12,000 turtles in 2018, with 85%–97% of that catch in the small‐scale fishery. We suggest that turtle management in the Solomon Islands, a nation with globally significant turtle breeding populations, should focus on sustainable management of small‐scale coastal fisheries.

ABSTRACT White‐tailed deer (Odocoileus virginianus) are a cervid species found mostly in the Americas. Managing white‐tailed deer requires understanding their relationship with the environment, which was characterized by Roseberry and Woolf (Wildlife Society Bulletin 1, 1998, 252) for all counties in Illinois, USA, who incorporated habitat quantity and quality in a deer habitat suitability index. However, this index was based on satellite imagery from 1996 and did not explore the smaller spatial scales used by deer. Our study addressed these gaps by developing a deer land cover utility (LCU) score for each TRS (township, range, and section), township, and county in Illinois based on the methodology outlined in Roseberry and Woolf (Wildlife Society Bulletin 1, 1998, 252) but using data from the National Land Cover Database (2001–2021). These deer LCU scores were validated against minimum deer population data using Bayesian regression with additional covariates relevant to hunting and deer density. These models performed well with Bayesian R2 values of 0.501 (TRS), 0.5 (township), and 0.969 (county). The regression coefficients for the deer LCU scores were statistically significant (95% credibility interval not containing 0) and positive at the TRS, township, and county levels, reflecting the expected relationship between minimum deer density and deer LCU. Predictions made by these regression models on new data were accurate, with the median absolute difference between the true and predicted values being 0.398 deer/km2 for TRS', 0.085 deer/km2 for townships, and 0.066 deer/km2 for counties. This deer LCU could be used in other studies about deer in Illinois or studies in which deer are a relevant factor such as investigations about deer disease or tick distribution. This modeling approach could also be adapted to different wild species, locations, and/or time periods for which land cover data is available.

ABSTRACT Environmental conditions in freshwater ecosystems are increasingly determined by human activity. Increased temperature and light intensity are among the anthropogenic stressors dramatically altering these ecosystems, for example, through deforestation that reduces canopy cover of riparian vegetation. Simultaneous exposure to multiple stressors complicates predictions of responses to environmental stressors due to potential interactions, yet the interaction between temperature and light intensity on feeding motivation remains poorly understood. Here, a fully factorial design was employed to investigate the combined effect of increased temperature and light intensity on the feeding motivation of a freshwater predator, the pike cichlid Saxatilia proteus. Strikes toward food items were used to quantify the subjects' motivation to feed. We found no effect of temperature or light intensity on feeding motivation, either individually or as an interaction. Our repeated measures design allowed us to test whether the predatory fish showed personality variation, i.e., consistent inter‐individual differences, in their motivation to feed. While the time taken to make the first strike was not consistently different between individuals, the number of strikes in 1 min, 3 min and the time taken for the 10th strike (which were strongly correlated to one another) was consistently different between individuals. This variation could not be explained by variation in body length, which had no effect as a main effect. Thus, we suggest that anthropogenic effects that alter the composition of individuals in a population of predators, for example selective harvesting, will have a greater ecological effect than direct short‐term effects of variability in environmental factors.

ABSTRACT Background Nationwide US data on readmission rates for patients with cirrhosis admitted with hepatorenal syndrome (HRS) is lacking. We reviewed 30‐day readmission rates after HRS‐related hospitalizations, the associated predictors of readmissions, and their impact on resource utilization and mortality in the United States. Methods We identified all adults admitted with HRS between 2016 and 2019 using the Nationwide Readmission database of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. The primary outcome was all‐cause 30‐day readmission rate. Secondary outcomes were inpatient mortality rate, predictors of readmission, and resource utilization. Results We identified 245 850 hospitalizations of patients admitted for HRS in the United States from 2016 to 2019. Of these, 214 890 met the inclusion criteria. Mean age was 59.16 years, and 61.31% were males. Medicare was the most common primary payer (44.82%) followed by Medicaid (25.58%). The readmission rate was 24.6% within 30 days of discharge from index hospitalization. The most common cause of readmission was alcoholic cirrhosis with ascites (14.87%), followed by sepsis (9.32%) and unspecified hepatic failure (9%). The in‐hospital mortality rate for index hospitalization was 29.52% and 14.35% among those readmitted within 30 days. The mean length of stay (12.33 days vs. 7.15 days, p

Abstract Foams are versatile by nature and ubiquitous in a wide range of applications, including padding, insulation, and acoustic dampening. Previous work established that foams 3D printed via Viscous Thread Printing (VTP) can in principle combine the flexibility of 3D printing with the mechanical properties of conventional foams. However, the generality of prior work is limited due to the lack of predictable process‐property relationships. In this work, a self‐driving lab is utilized that combines automated experimentation with machine learning to identify a processing subspace in which dimensionally consistent materials are produced using VTP with spatially programmable mechanical properties. In carrying out this process, an underlying self‐stabilizing characteristic of VTP layer thickness is discovered as an important feature for its extension to new materials and systems. Several complex exemplars are constructed to illustrate the newly enabled capabilities of foams produced via VTP, including 1D gradient rectangular slabs, 2D localized stiffness zones on an insole orthotic and living hinges, and programmed 3D deformation via a cable‐driven humanoid hand. Predictive mapping models are developed and validated for both thermoplastic polyurethane (TPU) and polylactic acid (PLA) filaments, suggesting the ability to train a model for any material suitable for material extrusion (ME) 3D printing.

Background There is strong interest in the evaluation of longer‐term outcome metrics for congenital heart diseases (CHDs); however, registries focus on postoperative metrics. Methods and Results Informed by user online discussion forums and scoping of national data, we selected sentinel CHDs and long‐term outcome metrics suitable for routine monitoring. We then developed sentinel CHD phenotypes and algorithms for identifying treatment pathway procedures using clinical codes. Finally, we calculated the metrics within a retrospective national cohort analysis. The 9 selected sentinel CHDs had a higher‐than‐average prevalence, typically involved surgery in infancy, and were associated with an increased risk of late mortality. The selected metrics of survival and reinterventions at 1, 5, and 10 years were both important and feasible. The cohort included 29 319 (41.3% of all operated CHD births) English and Welsh children born with sentinel CHDs in 2000 to 2022. Example metrics at age 10 years included: survival—hypoplastic left heart syndrome: 57.6% (95% CI, 54.9%–60.4%), functionally univentricular heart: 86.7% (95% CI, 84.6%–88.9%), transposition of the great arteries: 93.1% (95% CI, 92.2%–93.9%), pulmonary atresia: 81.0% (95% CI, 79.1%–82.9%), atrioventricular septal defect: 88.5% (95% CI, 87.5%–89.5%), tetralogy of Fallot: 95.1% (95% CI, 94.4%–95.8%), aortic stenosis: 94.4% (95% CI, 93.3%–95.6%), coarctation: 96.7% (95% CI, 96.2%–97.3%), and ventricular septal defect: 96.9% 95% CI, (96.4%–97.3%); and (2) cumulative incidence of reintervention—hypoplastic left heart syndrome : 54.5% (95% CI, 51.5%–57.3%), functionally univentricular heart: 57.3% (95% CI, 53.9%–60.5%), transposition of the great arteries: 20.9% (95% CI, 19.5%–22.3%), pulmonary atresia: 66.8% (95% CI, 64.2%–69.1%), atrioventricular septal defect: 21.6% (20.3%–23.0%), tetralogy of Fallot: 26.6% (95% CI, 25.2%–28.0%), aortic stenosis: 31.2% (95% CI, 28.8%–33.6%), coarctation: 19.8% (95% CI, 18.6%–21.1%), and ventricular septal defect: 6.1% (95% CI, 5.5%–6.8%). Conclusions It is feasible to report important long‐term outcomes of survival and reintervention for sentinel CHDs using routinely collected procedure records, adding value to national audit.

The National Heart, Lung, and Blood Institute convened a virtual workshop in September 2022 to discuss “Optimal Instruments for Measurement of Diet, Physical Activity, and Sleep.” This report summarizes the proceedings, identifying current research gaps and future directions for measuring different lifestyle behaviors in adult population‐based studies. Key discussions centered on integrating report‐based methods, like questionnaires, with device‐based assessments, including wearables and physiological measures such as biomarkers and omics to enhance self‐reported metrics and better understand the underlying biologic mechanisms of chronic diseases. Emphasis was placed on the need for data harmonization, including the adoption of standard terminology, reproducible metrics, and accessible raw data, to enhance the analysis through artificial intelligence and machine learning techniques. The workshop highlighted the importance of standardizing procedures for integrated behavioral phenotypes using time‐series data. These efforts aim to refine data accuracy and comparability across studies and populations, thereby advancing our understanding of lifestyle behaviors and their impact on chronic disease outcomes over the life course.

Abstract Urban landscapes play a crucial role in the health of freshwater ecosystems. The task of protecting and restoring urban freshwater waterways requires concerted efforts from all sectors of society, including volunteers. The recruitment and retention of volunteers is often a challenge for community environmental organizations as urban residents are diverse and influenced by a blend of personal, societal, and environmental factors. We surveyed a representative sample of 1901 urban residents across Aotearoa New Zealand and used the Behaviour Change Wheel framework and audience segmentation to understand the underlying factors influencing volunteering for waterway restoration projects and to identify potential target audiences to recruit new volunteers. We identified four segments within the target audience (“Supportive,” “Receptive but unsure,” “Hesitant and lack opportunity,” and “Reluctant”) each with its own unique profile of capabilities, opportunities, and motivations for volunteering. Recommendations for appropriate intervention designs to increase levels of volunteering include providing tailored messaging and events for those who are “Receptive but unsure” or “Hesitant and lack opportunity” and information about volunteering opportunities to “Supportive” individuals. This knowledge lays the groundwork for future initiatives focused on increasing urbanites' volunteering with community freshwater restoration groups.

Abstract Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance—LPL, APOC2, APOA5, LMF1, and GPIHBP1. Pathogenic variants in LPL, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%–90% of cases. FCS may present in infancy with hypertriglyceridemia‐induced acute pancreatitis and is challenging to manage both acutely and in the long‐term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia‐induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C>A (p.Tyr329Ter) and c.632C>A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat‐restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110–120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia‐induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence‐based recommendations.

Abstract Background Traditionally, 6‐month courses of prednisolone are used to treat steroid‐responsive meningitis‐arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life. Hypothesis/Objectives Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6‐month prednisolone protocol and a 6‐week protocol. Animals Forty‐four hospital cases from multiple referral centers in the United Kingdom (2015‐2019). Twenty of 44 were treated with the 6‐month protocol and 24/44 with the 6‐week protocol. Methods Prospective, randomized trial with 12‐month follow‐up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling. Results All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6‐month protocol and 9/24 (38%) of the 6‐week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40‐4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61‐3.48; P = 0.40). Conclusions and Clinical Importance “Short” 6‐week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.

Abstract The authors present spatio‐temporally resolved wideband measurements of Sub‐Terahertz (Sub‐THz) reflection coefficients in the frequency range of 92–110 GHz. A stochastic model for single reflection fixed links that is capable of modelling random scattering from small‐scale discontinuities such as those encountered in complex structures in walls and partitions of buildings is presented. The model auto‐regressively produces filter coefficients that are fed into an Infinite‐Impulse‐Response (IIR) filter which convolves them with the spatio‐temporal series in order to generate the next output sample based on previous observations. The IIR filter allows for flexible stochastic generation of samples, and its parameters can be adjusted as needed to suit different channel conditions. A total of 20 suitable start‐up filter coefficients are generated from 21.7 % of the sample size for each complex delay tap distribution, which corresponds to 50 complex instances of the channel. These coefficients are then utilised to validate the remaining measured sample set. The model is in quantitative agreement with measurement statistics and can be used to construct relatively simple modified reflection coefficients that can be used in micro‐cellular ray‐optical network planning tools.

Abstract Parks are an integral component of cities. Ensuring city residents have equitable and easy access to parks is crucial for human well‐being. In temperate climates, park accessibility is particularly important in the summer months when these green spaces provide an area to recreate, exercise and escape indoor temperatures and heat emanating from paved and built surfaces. However, there are well‐known disparities in park accessibility in cities globally that may threaten the health of city residents, especially with global warming. We examined some of the largest city parks (>50 ha) in Toronto, Canada, by comparing park activity, housing demographics and daily weather patterns. We found that parks that provided more green space area per resident were situated in neighbourhoods that had higher proportions of single‐detached housing, higher automobile use and fewer multistorey apartments. We also found a strong correlation between park activity with population density and the number of amenities in the park. Surprisingly, we found no relationship between park activity and daily weather patterns, although park use was higher on weekends and holidays. These results suggest denser communities are at a disadvantage because they have proportionately less park area within walking distance in addition to having no private green spaces (e.g. backyards). We recommend revising municipal zoning around certain parks and the creation of new green spaces as methods to balance park provisioning in the city. Our findings suggest that designing and maintaining accessible, amenity‐rich parks is an important strategy for promoting health and well‐being in urban populations. Read the free Plain Language Summary for this article on the Journal blog.

Abstract The use of patient‐reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self‐report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990–2023). Seven thousand four hundred thirty‐five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full‐text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty‐four (48%) were double‐blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty‐nine trials (78%) included multiple cancer types. Twenty‐seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4–96). The most frequent QOL measure was the EORTC QLQ‐C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well‐validated QOL measures, including cachexia‐specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co‐primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific‐based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures.

Abstract Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of

Abstract Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety‐nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C‐reactive protein (n = 22, 42.3%), interleukin‐6 (n = 16, 30.8%) and tumour necrosis factor‐α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin‐like growth factor binding protein 3 (IGFBP‐3) and insulin‐like growth factor 1 (IGF‐1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP‐3, IGF‐1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.

Abstract Consumer engagement and partnership are increasingly recognised as a significant component of healthcare planning, provision, quality improvement and research. This article provides an overview of consumer engagement embedded in two different projects: a quality improvement project and a research project. The considerations and steps taken to effectively engage and partner with consumers throughout both projects will be discussed such as the prompt for consumer engagement, how the consumer/s were recruited and their specific contributions. The commonly reported advantages and challenges as well as reflections on what we might do differently with the benefit of hindsight are presented, including time required by both consumers and health professionals; funding and remuneration; and reporting findings to the wider community. In demonstrating consumer engagement and our learnings, we aim to encourage further consumer engagement activities amongst medical radiation professionals.