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Guided by developmental models examining the legacy of childhood caregiving environments, we examined the longitudinal pattern of associations between harsh parenting and children's internalizing and externalizing symptoms across late childhood to late adolescence. Participants included 199 youth (48.7% female, 65.3% White, 32.2% Black, 2.5% biracial) and their mothers and fathers from a diverse range of socioeconomic backgrounds. The study utilized a multi-informant, longitudinal design including five waves of data (youths' mean ages were 9, 10, 11, 17, and 18 across waves). Harsh parenting at Age 9 predicted higher levels of (a) externalizing symptoms at Ages 11, 17, and 18 and (b) internalizing symptoms at Ages 17 and 18. Developmental sensitivity analyses revealed that the magnitude of the more distal association between early harsh parenting and later internalizing and externalizing symptoms was statistically stronger as compared to more proximal associations. Bidirectional analyses revealed that externalizing symptoms at Age 9 predicted harsh parenting at Ages 9, 10, 11, 17, and 18. Whereas links between harsh parenting and internalizing symptoms were consistent with a sleeper effects model, links between harsh parenting and externalizing symptoms provided some support for both enduring and sleeper effects models. Findings inform an understanding of youth developmental sensitivity to harsh parenting and the downstream consequences of harsh parenting. Results have important translational implications, including testing the long-term efficacy of therapeutic programs.

There is a well-documented interdependency between destructive interparental conflict (IPC) and parenting difficulties (i.e., spillover effect), yet little is known about the mechanisms that "carry" spillover between IPC and parenting. Guided by a cascade model framework, the current study used a longitudinal, multimethod, multi-informant design to examine a process model of spillover that tested whether parental executive functioning (working memory, cognitive flexibility, inhibitory control) served as a mediator of the prospective associations between IPC and subsequent changes in parenting over a 2-year period. Mothers and fathers were separated into differentiated models and multiple domains of parenting were examined (i.e., authoritarian discipline and scaffolding behavior). Participants included 231 families (both mothers and fathers of preschoolers). Race was reported as White (62%), Black (21%), Mixed (8%), Asian (3%), or Other (6%) and 14% considered their ethnicity to be Hispanic/Latino. Median household income was $65,000. Results indicated that for fathers, IPC indirectly predicted domain-general parenting difficulties (increased authoritarian parenting and decreased scaffolding) via deficits in paternal cognitive flexibility (but not inhibitory control or working memory). In mothers, IPC directly predicted domain-specific parenting difficulties (decreased scaffolding only) that did not operate via maternal executive functions. Notably, these effects occurred over and above the influence of parental socioeconomic status. This study constitutes a first step toward documenting parental executive functioning as a mechanism underlying the spillover of IPC to the parent-child relationship. Family interventions intended to interrupt IPC spillover should emphasize father involvement and consider targeting parental executive functions as change mechanisms.

Using a content analysis methodology, we examined 15 peer-reviewed articles published between 2009 and 2019 that used qualitative and mixed methods approaches to explore how college and university students experience food insecurity. Concerningly, there was limited variety in the methods employed across these articles and more discussion of methodology was needed. Despite this, our analysis of student statements in these articles yielded three common themes: (1) co-occurring basic needs; (2) academic, physical, psychological, and social effects of food insecurity; and (3) institutional satisfaction and/or critique. We include implications for research and practice.Context and implicationsRationale for the studyFew qualitative studies centre students' food insecurity experiences in the United States. We examined available research to unearth commonalities across student narratives while connecting food insecurity to broader social class inequality in higher education.Why the new findings matterOur findings underscore the urgent need for additional qualitative food insecurity scholarship that foregrounds student voices. Future researchers examining food insecurity should consider: (a) the nuances of on-campus food insecurity, (b) the impact of food insecurity on student success, and (c) the linkages between food insecurity and social class in higher education.Implications for policy makersCampus leaders and policy makers can help address campus food insecurity by building holistic wraparound systems to support the multi-faceted needs of students facing food insecurity. To do this, policy makers and leaders must begin to understand food insecurity as more than a statistic and acknowledge the human experiences of those it affects.

This study uses a critical consciousness framework to understand the experiences of higher education and student affairs (HESA) graduate students in an elective Diversity in HIED course. We drew from narrative inquiry to analyze data from selected student coursework in online discussion board conversations and journal entries. Students demonstrated building a foundation for engagement with critical consciousness, particularly through themes of interest in the emotions that surfaced during the course, reconceptualizing "diversity," and how to apply their learning to HESA practice. Participant learning reflected that HESA graduate programs can foster an important foundation for personal and professional development in this area. This knowledge can help faculty and supervisors support HESA graduate students' learning and preparation for active engagement regarding critical consciousness in HESA practice.

Abstract Background Quantitative mapping of the brain’s metabolism is a critical tool in studying and diagnosing many conditions, from obesity to neurodegenerative diseases. In particular, noninvasive approaches are urgently required. Recently, there have been promising drug development approaches for the treatment of disorders related to glucose metabolism in the brain and, therefore, against obesity-associated diseases. One of the most important drug targets to emerge has been the Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R). GLP and GLP-1R play an important role in regulating blood sugar and maintaining energy homeostasis. However, the macroscopic effects on brain metabolism and function due to the presence of GLP-1R are unclear. Methods To explore the physiological role of GLP-1R in mouse brain glucose metabolism, and its relationship to brain function, we used three methods. We used deuterium magnetic resonance spectroscopy (DMRS) to provide quantitative information about metabolic flux, fluorodeoxyglucose positron emission tomography (FDG-PET) to measure brain glucose metabolism, and resting state-functional MRI (rs-fMRI) to measure brain functional connectivity. We used these methods in both mice with complete GLP-1R knockout (GLP-1R KO) and wild-type C57BL/6N (WT) mice. Results The metabolic rate of GLP-1R KO mice was significantly slower than that of WT mice (p = 0.0345, WT mice 0.02335 ± 0.057 mM/min, GLP-1R KO mice 0.01998 ± 0.07 mM/min). Quantification of the mean [18F]FDG signal in the whole brain also showed significantly reduced glucose uptake in GLP-1R KO mice versus control mice (p = 0.0314). Observing rs-fMRI, the functional brain connectivity in GLP-1R KO mice was significantly lower than that in the WT group (p = 0.0032 for gFCD, p = 0.0002 for whole-brain correlation, p

Across undergraduate STEM learning contexts in several countries, students' intrapersonal attributes of epistemic beliefs, self-efficacy beliefs, intrinsic motivation, and sense of identity have been found to influence learning and to change in response to educational practices. However, research can mask individual and demographic differences in student's attributes that may moderate or mediate the relationship between educational practices and learning outcomes. We employed variable-centered and person-centered methods to examine individual and demographic differences in changes in students' intrapersonal attributes and patterns of interrelationship among attributes with a study sample of students (N = 4,500) in 14 STEM undergraduate courses (8 biology, 4 chemistry, and 2 statistics) at three research universities in the United States. Variable-centered analyses revealed overall increases in students' science self-efficacy beliefs and epistemic beliefs even though these outcomes were not intentionally targeted as learning objectives. However, person-centered analyses indicated that not all students experienced these gains. For example, self-identified Asian/Pacific Islander and Black students were more likely to be members of groups demonstrating a decrease in science self-efficacy, whereas Asian/Pacific Islander students and men were less likely to be members of the subgroup with consistently evaluativist epistemic beliefs and higher GPAs. Using latent profile analysis (LPA), we identified five distinct student profiles that reflected different patterns of interrelationship of epistemic beliefs, science and writing self-efficacy beliefs, and science identity. We discuss the implications of these findings for educational practices, particularly with regard to intentionally fostering diverse students' self-efficacy, sense of identity, and adaptive epistemic beliefs.

In the United States, HIV disproportionately affects people 13-45 years old, people of color, people in the south, and men who have sex with men. Given the growing number of postsecondary students within these demographic groups, this presents an equity issue and raises concerns for how higher education researchers and practitioners choose to engage problems of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in U.S. college contexts. Using a content analysis methodology and Endarkened Feminist Epistemological lens, we examined a decade of HIV/AIDS-related research published in 113 higher education journals. Our findings suggest a generally limited focus on HIV/AIDS in college contexts and overrepresentation of quantitative methods in available scholarships. Furthermore, despite widening HIV/AIDS diagnosis gaps, researchers rarely nuanced identity and most often focused on individual choices rather than systemic structures.

“Giant” or core/thick-shell quantum dots (gQDs) are an important class of solid-state quantum emitter characterized by strongly suppressed blinking and photobleaching under ambient conditions, and reduced nonradiative Auger processes. Together, these qualities provide distinguishing and useful functionality as single- and ensemble-photon sources. For many applications, operation at elevated temperatures and under intense photon flux is desired, but performance is strongly dependent on the synthetic method employed for thick-shell growth. Here, a comprehensive analysis of gQD structural properties “from the inside out” as a function of shell-growth method is reported: successive ionic layer adsorption and reaction (SILAR) and high-temperature continuous injection (HT-CI), or sequential combinations of the two. Key correlations across synthesis methods, structural features (interfacial alloying, stacking-fault density and surface-ligand identity), and performance metrics (quantum yield, single-gQD photoluminescence under thermal/photo stress, charging behavior and quantum-optical properties) are identified. Surprisingly, it is found that interfacial alloying is the strongest indicator of gQD stability under stress, but this parameter is not the determining factor for Auger suppression. Furthermore, quantum yield is strongly influenced by surface chemistry and can approach unity even in the case of high shell-defect density, while introduction of zinc-blende stacking faults increases the likelihood that a gQD exhibits charged-state emission.

Abstract Alloying in metal castings is one of the principal methods of strengthening an alloy for various structural and functional applications, but very rarely does it modify an alloy’s elastic modulus. We report a methodology of combining isostructural Laves phases to form a multi-component, high symmetry, isotropic phase that was discovered to enhance the elastic modulus of a cast aluminum alloy to 91.5 ± 7.4 GPa. Flux grown single crystals of the rhombicuboctahedron phase (RCO), so named for the observed morphology, were used to enhance understanding of the structure and mechanical properties of the phase. The pure RCO phase’s structure and site occupancies were co-refined using x-ray and neutron diffraction. Dynamic nanomechanical testing of the cast alloy shows the primary RCO phase has a high, relatively isotropic, elastic modulus. This RCO containing aluminum alloy is found to have a specific modulus that exceeds that of the leading Al, Mg, Steel, and Ti alloys.

Abstract Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically‐based PK (PBPK) models are an attractive alternative that can account for physiologic‐, genetic‐, and drug‐specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label‐suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age‐associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration‐recommended weight‐tiered dosing. Simulated concentration–time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight‐tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited.

Abstract Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA’s Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87Rb atoms in the CAL AI. A three-pulse Mach–Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space.

Abstract Critically endangered Hooded Vultures (Necrosyrtes monachus Temminck, 1823), like many vulture species globally, are experiencing rapid population declines due to anthropogenic factors such as poisonings, human persecution, trading for belief-based use, and habitat loss/degradation. The Hooded Vulture is widespread across sub-Saharan Africa. Although it is considered one of the most abundant vultures in West Africa, this vulture species is less common in East and southern Africa, with the population at the southern-most edge of the distribution (in South Africa and Eswatini) estimated at only 100–200 mature individuals. The distribution of Hooded Vultures has contracted dramatically in southern Africa, with breeding populations largely confined to protected areas such as the Greater Kruger National Park. This study aimed to investigate the genetic diversity of the southern African range-edge population and assess if the recent contraction in the distribution has resulted in the population experiencing a genetic bottleneck. Sixteen microsatellite loci were amplified for samples collected along the Olifants River in the Greater Kruger National Park (n = 30). The genetic diversity in the South African population was compared to samples (n = 30) collected in Ghana, where Hooded Vultures are more abundant. Contrary to expectations, the South African peripheral Hooded Vulture population showed higher levels of heterozygosity (HO = 0.495) than the Ghanaian population (HO = 0.315). Neither population showed signs of recent bottleneck events when tested using demographic modelling and Approximate Bayesian computation (ABC). However, both populations showed high levels of inbreeding and relatedness. Our results suggest that despite being a small peripheral population, the South African Hooded Vulture population showed a similar level of genetic diversity as individuals sampled from a core population within the species distribution (in Ghana). This study supports the need for Hooded Vulture conservation efforts in the southern African region and highlights the evolutionary importance of range-edge populations.

Abstract A major goal in evolutionary biology is to elucidate common principles that drive human and other animal societies to adopt either a warlike or peaceful nature. One proposed explanation for the variation in aggression between human societies is the democratic peace hypothesis. According to this theory, autocracies are more warlike than democracies because autocratic leaders can pursue fights for private gain. However, autocratic and democratic decision-making processes are not unique to humans and are widely observed across a diverse range of non-human animal societies. We use evolutionary game theory to evaluate whether the logic of democratic peace may apply across taxa; specifically adapting the classic Hawk-Dove model to consider conflict decisions made by groups rather than individuals. We find support for the democratic peace hypothesis without mechanisms involving complex human institutions and discuss how these findings might be relevant to non-human animal societies. We suggest that the degree to which collective decisions are shared may explain variation in the intensity of intergroup conflict in nature.

Abstract Opioid withdrawal is a liability of chronic opioid use and misuse, impacting people who use prescription or illicit opioids. Hyperactive autonomic output underlies many of the aversive withdrawal symptoms that make it difficult to discontinue chronic opioid use. The locus coeruleus (LC) is an important autonomic centre within the brain with a poorly defined role in opioid withdrawal. We show here that pannexin-1 (Panx1) channels expressed on microglia critically modulate LC activity during opioid withdrawal. Within the LC, we found that spinally projecting tyrosine hydroxylase (TH)-positive neurons (LCspinal) are hyperexcitable during morphine withdrawal, elevating cerebrospinal fluid (CSF) levels of norepinephrine. Pharmacological and chemogenetic silencing of LCspinal neurons or genetic ablation of Panx1 in microglia blunted CSF NE release, reduced LC neuron hyperexcitability, and concomitantly decreased opioid withdrawal behaviours in mice. Using probenecid as an initial lead compound, we designed a compound (EG-2184) with greater potency in blocking Panx1. Treatment with EG-2184 significantly reduced both the physical signs and conditioned place aversion caused by opioid withdrawal in mice, as well as suppressed cue-induced reinstatement of opioid seeking in rats. Together, these findings demonstrate that microglial Panx1 channels modulate LC noradrenergic circuitry during opioid withdrawal and reinstatement. Blocking Panx1 to dampen LC hyperexcitability may therefore provide a therapeutic strategy for alleviating the physical and aversive components of opioid withdrawal.

ABSTRACT Numbers of Critically Endangered Hooded Vultures (Necrosyrtes monachus Temminck 1823) are declining across their distribution. The range‐edge population in South Africa is one of the smallest populations with only 100–200 mature individuals. In South Africa, Hooded Vultures nest solitarily in loose colonies (mean distance between nests 0.76 km) along water courses. Basic ecological information, such as breeding behaviour, is still lacking for the species. In this study, we examine the relatedness and nest turnover of nesting individuals along the Olifants River and other locations in the Lowveld of South Africa by sampling nests over five consecutive years. A key hypothesis tested is whether communal roosting sites function as information‐sharing hubs, a phenomenon that has been seen in Cape Vultures (Gyps coprotheres) and other cliff‐nesting vultures. Theory suggests that information sharing occurs more frequently between closely related individuals. If true, we expect distance between nests and genetic relatedness to be positively correlated and individuals to use the same nests over multiple years. Naturally moulted feathers (n = 108) were collected below nests over five consecutive years, and 14 microsatellite loci markers were used to measure genetic relatedness. Mantel tests performed correlating distance between nests to relatedness coefficient estimators TrioML (r = 0.032, R2 = 0.001, p = 0.224) and LynchRD (r = 0.007, R2 = 0.00005, p = 0.403), found no statistical correlation. The Mantel test performed using Nei's genetic distance and distance between nests did show a negative correlation (r = −0.108, R2 = 0.0117, p‐value = 0.012), indicating that individuals that were more closely related tended to breed further away. No nest reuse was found in this study. We thus believe that these loose colonies do not act as food‐finding hubs, but rather that the Olifants River is an important breeding site for these birds.

Cardiovascular disease (CVD) is one of the top contributors to global disease burden. Meeting the physical activity guidelines can effectively control and prevent several CVD risk factors, including obesity, hypertension and diabetes mellitus. The effects of climate change are multifactorial and have direct impacts on cardiovascular health. Increasing ambient temperatures, worsening air and water quality and urbanisation and loss of greenspace will also have indirect effects of cardiovascular health by impacting the ability and opportunity to participate in physical activity. A changing climate also has implications for large scale sporting events and policies regarding risk mitigation during exercise in hot climates. This review will discuss the impact of a changing climate on cardiovascular health and physical activity and the implications for the future of organised sport.

The holobiont theory of evolution explains how individuals are deeply symbiotic with their gut microbes, such that microbes are adapted to influence host metabolism, immunity and behaviour, as signalled from the gut to the brain. For eusocial taxa like the Western honey bee (Apis mellifera), this brain-gut axis may scale up from the individual to affect entire colonies. Here, we examine how microbial supplementation of honey bee feeds could manipulate the brain-gut axis to affect hygienic and other social behaviours relevant to beekeeping, such as foraging, recruitment (dance language) and defence. To illustrate this concept, we focus on various lactic acid-producing bacteria that can synthesize neurotransmitters such as octopamine, dopamine, serotonin and γ-aminobutyric acid, which can influence an individual bee’s behavioural cycles and responsiveness to environmental cues. If the behaviour of a worker bee can be deliberately manipulated, and this effect multiplied across many workers, microbial neurotherapeutics could conceivably render colonies more behaviourally responsive to symptoms of disease, or more motivated to forage or possibly less aggressive towards beekeepers. Drawing from the scientific literature, we infer how microbial supplements, such as neurostimulatory or neurosuppressive probiotics, could be applied or even engineered to co-opt the brain-gut axis to bolster colony health or improve performance. The mechanistic link between the gut microbiota and the collective social behaviour of single colonies remains an understudied aspect of honey bee social biology with relevance to apiculture.

Long-term wildlife research and monitoring programs strive to maintain consistent data collections and analytical methods. Incorporating new techniques is important but can render data sets incongruent and limit their potential to discern trends in demographic parameters. Integrated population models (IPMs) can address these limitations by combining data sources that may span different periods into a unified statistical framework while providing a holistic view of population dynamics. We developed an IPM in a Bayesian framework for grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem. We coupled demographic data with multiple, independent population count data to link annual changes in abundance with vital rates over 4 decades (1983–2023). Abundance increased threefold from an estimated 270 individuals in 1984 to 1030 individuals in 2023. Parameter estimates indicated survival of bears ≥2 years of age was high, contributing to robust population growth during the 1980s (λ = 1.023 [50 % interquartile range = 0.993–1.082]) and 1990s (λ = 1.064 [1.023–1.103]). A slowing of population growth started around 2000 (2000s: λ = 1.030 [0.989–1.068]) and continued into the 2010s (λ = 1.021 [0.985–1.057]), due primarily to reductions in survival of bears

Abstract This cross-sectional study investigated differences in the plasma metabolome in two groups of adults that were of similar age but varied markedly in body composition and dietary and physical activity patterns. Study participants included 52 adults in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females). The results using an extensive untargeted ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomics analysis with 10,535 metabolite peaks identified 486 important metabolites (variable influence on projections scores of VIP ≥ 1) and 16 significantly enriched metabolic pathways that differentiated LIFE and CON groups. A novel metabolite signature of positive lifestyle habits emerged from this analysis highlighted by lower plasma levels of numerous bile acids, an amino acid profile characterized by higher histidine and lower glutamic acid, glutamine, β-alanine, phenylalanine, tyrosine, and proline, an elevated vitamin D status, higher levels of beneficial fatty acids and gut microbiome catabolism metabolites from plant substrates, and reduced levels of N-glycan degradation metabolites and environmental contaminants. This study established that the plasma metabolome is strongly associated with body composition and lifestyle habits. The robust lifestyle metabolite signature identified in this study is consistent with an improved life expectancy and a reduced risk for chronic disease.

Abstract In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus–like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.

Some yellow-colored market classes of dry bean (Phaseolus vulgaris L.) are valued by consumers as an easy-to-digest, fast cooking alternative to darker colored red and black beans, which in comparison generally have longer cooking times and reduced iron bioavailability. There is evidence that the cooking time of yellow beans is linked to the dietary fiber content and may also contribute to nutrient digestibility and bioavailability. Therefore, 52 fast-, moderate-, and slow-cooking yellow beans with diverse iron bioavailability from five market classes (Amarillo, Canario, Green-yellow, Manteca, and Mayocoba) were selected for total dietary fiber (TDF) analysis. TDF was measured as insoluble (IDF) + soluble (SDF) + oligosaccharides (OLIGO) using method AOAC2011.25. Wide variations in the concentrations of IDF (16.0–23.1%), SDF (1.6–7.7%), OLIGO (1.5–3.4%), and TDF (20.6–31.3%) were detected among the yellow beans with various cooking times. Lower concentrations of IDF in yellow beans were associated with shorter cooking times and higher iron bioavailability. The larger sized Andean yellow beans had more SDF than Middle American. One Mayocoba breeding line from Puerto Rico, PR1146-124, had 42% less OLIGOs than average, and may be useful for breeding low-flatulence beans for consumer acceptability. Fast cooking yellow beans provide the same SDF and OLIGO concentrations as yellow beans with longer cooking times but have the added benefit of shorter cooking times (convenience) and provide more bioavailable iron after cooking.

Background Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity. Methods The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate Anticipated outcomes Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through in-person meetings with caregivers and regulatory bodies, presentations at conferences and in peer-reviewed journals.

Introduction There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.Methods and analysis MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0–6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur.Ethics and dissemination The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numbers NCT03387670; ISRCTN82598726.

Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1G93A mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.

Abstract Objective Commonly used terms like “obese person” have been identified as stigmatizing by those with lived experience. Thus, this study sought to revise a commonly used measure of weight stigmatizing attitudes, the Attitudes Toward Obese Persons (ATOP) scale. Methods The original terminology in the 20‐item ATOP (e.g., “obese”) was compared to a modified version using neutral terms (e.g., “higher weight”). Participants (N = 832) were randomized to either receive the original or modified ATOP. Results There was a statistically significant difference, with a small effect size (d = −0.22), between the scores of participants who received the original ATOP (M = 69.25) and the modified ATOP (M = 72.85), t(414) = −2.27, p = 0.024. Through principal component analysis, the modified ATOP was best used as a brief, 8‐item unidimensional measure. In a second sample, confirmatory factor analysis verified the fit of the brief, 8‐item factor structure. Conclusions Findings suggest that a modified, brief version of the ATOP (ATOP‐Heigher Weight; ATOP‐HW) with neutral language is suitable for assessing negative attitudes about higher‐weight people. The ATOP‐HW may slightly underestimate weight stigma compared to the original ATOP, or the language in the ATOP may magnify negative attitudes. Further examination of the terminology used in weight stigma measures is needed to determine how to best assess weight stigma without reinforcing stigmatizing attitudes. The present study's findings suggest that the use of neutral terms in measures of anti‐fat bias is a promising solution that warrants further investigation.

Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from insulin deficiency due to autoimmune loss of pancreatic β cells. In addition to β cell destruction, it is now accepted that β cell stress and dysfunction, such as senescence, plays a crucial role in the development of the disease. Accumulation of senescent β cells occurs during development of T1D in humans and contributes to the progression of T1D in the nonobese diabetic (NOD) mouse model. Senescent β cells are thought to exacerbate the inflammatory response within the islets by production and secretion of senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) from β cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts β cell EV cargo. In this minireview, we discuss emerging evidence that EV cargo proteins and miRNAs associated with senescence could contribute to the development of T1D and could suggest potential biomarkers and therapeutic targets for the regulation of SASP and elimination of senescent β cells in T1D. Future investigation exploring the intricate relationship between β cell senescence, EVs and miRNAs could pave the way for the development of novel diagnostic techniques and therapeutic interventions.

Abstract Farming practices of the past century have dramatically increased annual crop yields to unprecedented levels but have consequentially created increasing ecological and public health concerns, posing a long‐term threat to global food security. Soil tillage and chemical inputs perpetuate soil erosion, biodiversity loss, wetlands eutrophication, carbon emissions, and other farming stressors. Concomitantly, accompanying poor dietary patterns and malnutrition increase the risk for chronic diseases, such as cardiovascular diseases, obesity, type 2 diabetes, and cancer, which account for greater than 70% of global mortality per annum. Altogether, such annual monocropping systems exacerbate food insecurity, necessitating action across the fields of public health, agriculture, nutrition, medicine, and environmental ecology, that is, a transdisciplinary approach. Herein, we argue that the perennialization of crops creates an opportunity to address the challenges of environmental sustainability and nutritional adequacy economically. Unlike annuals, perennial crops have deeper roots for increased drought tolerance and reduced needs for fertilization and irrigation. Adopting perenniality can result in greater drought tolerance and improved soil health while reducing erosion, farming labor, and seed purchasing. Furthermore, perennializing novel staple crops may offer a superior and diverse dietary profile of phytochemicals, fiber, and macronutrients compared to conventional annuals. Instead of traditional perennial tree crops, we focus on intermediate wheatgrass Kernza® (Thinopyrum intermedium) and sunflowers (Helianthus tuberosus, H. maximiliani, and Silphium integrifolium) as exemplars of perennial staple food crops for grain and oil, respectively, at different stages of perennial crop commercialization. Ultimately, we discuss how integrating perenniality has the potential to revolutionize global agriculture and address food security concerns for the remainder of the 21st century.

As a new type of semiconductor laser, photonic crystal surface-emitting lasers (PCSELs) feature large-area single-mode surface emission with high power and high beam quality. The unique features of single-mode lasing over a large area active region are implemented by the in-plane optical feedback from two-dimensional (2D) photonic crystal cavities. In larger PCSEL cavities, the lasing gain threshold becomes similar for the fundamental and high-order modes, which degrades single-mode operation. Here, we investigate the impact of carrier injection on PCSEL modes by controlling the injection area and the gain mode interaction. Optical and electrical simulations are carried out to calculate the gain mode overlapping factor for different p electrode designs. We fabricated 250 × 250 µm2 photonic crystal cavities with different p electrode sizes for injection area control. The PCSEL device characterization results show that devices with an electrode size to cavity side length ratio of 0.6 have the maximum slope efficiency and a lower lasing threshold with a single lobe beam profile. Such selective carrier injection can also provide gain-guided resonance in the PCSEL cavities and enhance optical gain in the fundamental mode while suppressing gain in the high-order modes.

Introduction Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia’s hepatitis C elimination targets.Methods and analysis A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models.Ethics and dissemination The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals.Trial registration number NCT05016609.Trial progression The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

Abstract Background Cotton accounts for 80% of the global natural fibre production. Its leaf hairiness affects insect resistance, fibre yield, and economic value. However, this phenotype is still qualitatively assessed by visually attributing a Genotype Hairiness Score (GHS) to a leaf/plant, or by using the HairNet deep-learning model which also outputs a GHS. Here, we introduce HairNet2, a quantitative deep-learning model which detects leaf hairs (trichomes) from images and outputs a segmentation mask and a Leaf Trichome Score (LTS). Results Trichomes of 1250 images were annotated (AnnCoT) and a combination of six Feature Extractor modules and five Segmentation modules were tested alongside a range of loss functions and data augmentation techniques. HairNet2 was further validated on the dataset used to build HairNet (CotLeaf-1), a similar dataset collected in two subsequent seasons (CotLeaf-2), and a dataset collected on two genetically diverse populations (CotLeaf-X). The main findings of this study are that (1) leaf number, environment and image position did not significantly affect results, (2) although GHS and LTS mostly correlated for individual GHS classes, results at the genotype level revealed a strong LTS heterogeneity within a given GHS class, (3) LTS correlated strongly with expert scoring of individual images. Conclusions HairNet2 is the first quantitative and scalable deep-learning model able to measure leaf hairiness. Results obtained with HairNet2 concur with the qualitative values used by breeders at both extremes of the scale (GHS 1-2, and 5-5+), but interestingly suggest a reordering of genotypes with intermediate values (GHS 3-4+). Finely ranking mild phenotypes is a difficult task for humans. In addition to providing assistance with this task, HairNet2 opens the door to selecting plants with specific leaf hairiness characteristics which may be associated with other beneficial traits to deliver better varieties.

Abstract Background People with psoriasis live with other long‐term conditions (co‐morbidities) that affect their use of healthcare, but the scale of this is not well characterised. Objectives Estimate the concurrent prevalence of co‐morbidities known to affect the use of healthcare in people living with psoriasis in England. Methods A retrospective cohort study using linked data from the UK's Clinical Practice Research Datalink with Hospital Episode Statistics, Office for National Statistics mortality records, and Index of Multiple Deprivation 2010. A cohort of adults (≥18 years) with psoriasis was matched with a comparator cohort of individuals based on age, sex and registered general practice between April 2007 and December 2017. A predefined list of 21 co‐morbidities was selected from a published measure: the Cambridge Multimorbidity Index (CMI). Descriptive analysis describes prevalence with statistical tests (t tests; two‐sample proportions test) of difference for selected variables. Results The study cohort comprised 372,949 individuals (54,817 psoriasis; and 318,132 matched‐comparator). The calculated CMI general score was statistically higher at 0.54 (standard deviation: 0.9) for psoriasis compared with 0.39 (standard deviation: 0.75) for the matched comparator (t test; p

Purpose – The vibration of the rails is a significant source of railway rolling noise, often forming the dominant component of noise in the important frequency region between 400 and 2000 Hz. The purpose of the paper is to investigate the influence of the ground profile and the presence of the train body on the sound radiation from the rail. Design/methodology/approach – Two-dimensional boundary element calculations are used, in which the rail vibration is the source. The ground profile and various different shapes of train body are introduced in the model, and results are observed in terms of sound power and sound pressure. Comparisons are also made with vibro-acoustic measurements performed with and without a train present. Findings – The sound radiated by the rail in the absence of the train body is strongly attenuated by shielding due to the ballast shoulder. When the train body is present, the sound from the vertical rail motion is reflected back down toward the track where it is partly absorbed by the ballast. Nevertheless, the sound pressure at the trackside is increased by typically 0–5 dB. For the lateral vibration of the rail, the effects are much smaller. Once the sound power is known, the sound pressure with the train present can be approximated reasonably well with simple line source directivities. Originality/value – Numerical models used to predict the sound radiation from railway rails have generally neglected the influence of the ground profile and reflections from the underside of the train body on the sound power and directivity of the rail. These effects are studied in a systematic way including comparisons with measurements.

Abstract Synaptic receptors respond to neurotransmitters by opening an ion channel across the post-synaptic membrane to elicit a cellular response. Here we use recent Torpedo acetylcholine receptor structures and functional measurements to delineate a key feature underlying allosteric communication between the agonist-binding extracellular and channel-gating transmembrane domains. Extensive mutagenesis at this inter-domain interface re-affirms a critical energetically coupled role for the principal α subunit β1-β2 and M2-M3 loops, with agonist binding re-positioning a key β1-β2 glutamate/valine to facilitate the outward motions of a conserved M2-M3 proline to open the channel gate. Notably, the analogous structures in non-α subunits adopt a locally active-like conformation in the apo state even though each L9’ hydrophobic gate residue in each pore-lining M2 α-helix is closed. Agonist binding releases local conformational heterogeneity transitioning all five subunits into a conformationally symmetric open state. A release of conformational heterogeneity provides a framework for understanding allosteric communication in pentameric ligand-gated ion channels.

Abstract A metabotropic glutamate receptor coupled to phospholipase D (PLD‐mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch‐evoked firing. We report here the first identification of this PLD‐mGluR protein, by capitalizing on its expression in primary mechanosensory terminals, developing an enriched source, pharmacological profiling to identify an optimal ligand, and then functionalizing it as a molecular tool. Evidence from immunofluorescence, western and far‐western blotting indicates PLD‐mGluR is homomeric GluK2, since GluK2 is the only glutamate receptor protein/receptor subunit present in spindle mechanosensory terminals. Its expression was also found in the lanceolate palisade ending of hair follicle, also known to contain the PLD‐mGluR. Finally, in a mouse model with ionotropic function ablated in the GluK2 subunit, spindle glutamatergic responses were still present, confirming it acts purely metabotropically. We conclude the PLD‐mGluR is a homomeric GluK2 kainate receptor signalling purely metabotropically and it is common to other, perhaps all, primary mechanosensory endings.

Traumatic brain injury-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines, especially epinephrine, although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury. Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate, blood pressure, and blood flow to the hindlimb muscles. Therefore, the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in several function-specific central nervous system regions in rats. Following three repeated blast injuries at 3-day intervals, the hippocampus, motor cortex, locus coeruleus, vestibular nuclei, and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector coupled with high-performance liquid chromatography. Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age- and sex-matched sham controls. In other function-specific central nervous system regions, although the epinephrine levels were slightly altered following blast-induced traumatic brain injury, they were not statistically significant. These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function. This is the first report to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Corn (Zea mays L.) silage yield monitor data offer crucial insights into spatial and temporal yield variability. However, equipment’s sensor malfunctioning can result in data loss, and yield sensor systems are expensive to purchase and maintain. In this study, we analyzed corn silage yield data from two fields and three years each for two dairy farms (Farm A and B). We aimed to explore the potential of integrating high-resolution satellite data, topography, and climate data with machine learning models to estimate missing yield data for a field or a year. Our objectives were to identify key yield-explaining features and assess the accuracy of different machine learning models in estimating silage yield. Results showed that the features differed among farms with a Two-Band Enhanced Vegetation Index, EVI2 (Farm A), and elevation (Farm B) emerging as the most prominent predictors. Ensemble-based models like XGBoost, Random Forest, and Extra Tree regressors exhibited superior predictive performance. However, XGBoost performed poorly when applied to unseen fields or years, whereas Extra Tree regressor, followed closely by Random Forest, emerged as a more reliable model for predicting missing data. Despite achieving reasonable accuracy, the best performance for estimating data for a missing field (6.46 Mg/ha) and year (5.51 Mg/ha) fell short of the acceptable error threshold of 4.9 Mg/ha currently used in state policy to evaluate if a management change resulted in a yield increase. These findings emphasize the need for higher-resolution data and extended years of yield records to better capture the trends in farm-scale yield applications.

Explosion monitoring is performed by infrasound and seismoacoustic sensor networks that are distributed globally, regionally, and locally. However, these networks are unevenly and sparsely distributed, especially at the local scale, as maintaining and deploying networks is costly. With increasing interest in smaller-yield explosions, the need for more dense networks has increased. To address this issue, we propose using smartphone sensors for explosion detection as they are cost-effective and easy to deploy. Although there are studies using smartphone sensors for explosion detection, the field is still in its infancy and new technologies need to be developed. We applied a machine learning model for explosion detection using smartphone microphones. The data used were from the Smartphone High-explosive Audio Recordings Dataset (SHAReD), a collection of 326 waveforms from 70 high-explosive (HE) events recorded on smartphones, and the ESC-50 dataset, a benchmarking dataset commonly used for environmental sound classification. Two machine learning models were trained and combined into an ensemble model for explosion detection. The resulting ensemble model classified audio signals as either “explosion”, “ambient”, or “other” with true positive rates (recall) greater than 96% for all three categories.

Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versushost disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (n = 19) and allogeneic (n = 13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (OR 3.65, 95%CI 2.18-6.10) and overall survival (HR 1.38, 95%CI 1.20-1.58) in autologous HCT and relapse (HR 0.80, 95%CI 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision-making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.

Evidence triangulation may help identify the impact of study design elements on study findings and to tease out biased results when evaluating potential causal relationships; however, methods for triangulating epidemiologic evidence are evolving and have not been standardized. Building upon key principles of epidemiologic evidence triangulation and risk of bias assessment, and responding to the National Academies of Sciences, Engineering, and Medicine (NASEM) call for applied triangulation examples, the objective of this manuscript is to propose a triangulation framework and to apply it as an illustrative example to epidemiologic studies examining the possible relationship between occupational formaldehyde exposure and risk of myeloid leukemias (ML) including acute (AML) and chronic (CML) types.A nine-component triangulation framework for epidemiological evidence was developed incorporating study quality and ROB guidance from various federal health agencies (i.e., US EPA TSCA and NTP OHAT). Several components of the triangulation framework also drew from widely used epidemiological analytic tools such as stratified meta-analysis and sensitivity analysis. Regarding the applied example, fourteen studies were identified and assessed using the following primary study quality domains to explore potential key sources of bias: 1) study design and analysis; 2) study participation; 3) exposure assessment; 4) outcome assessment; and 5) potential confounding. Across studies, methodological limitations possibly contributing to biased results were observed within most domains. Interestingly, results from one study – often providing the largest and least-precise relative risk estimates, likely reflecting study biases, deviated from most primary study findings indicating no such associations. Triangulation of epidemiological evidence appears to be helpful in exploring inconsistent results for the identification of study results possibly reflecting various biases. Nonetheless, triangulation methodologies require additional development and application to real-world examples to enhance objectivity and reproducibility.