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Operating room inventories typically involve hundreds of surgical items. Managers require very high service levels since the cost of shortages can be excessive up to and including cancelling surgery. From our experience, many inventory managers rely on manual approaches and intuition to set inventory control parameters. Although there are classical theoretical methods available for deriving "optimal" inventory policies, these classical methods rely on assumptions that do not accurately represent typical operating room inventories. Using 5 years of data from a large Canadian hospital, we use simulation and a simple search heuristic to find the optimal (s, S) ordering policy and show that 1) current hospital methods dramatically underperform with respect to service level and 2) there are significant savings to be realised over the best available classical theoretical models. An example case testing potential lead time changes is discussed. [ABSTRACT FROM AUTHOR]

Objectives: To examine the rate of skin color reporting in randomized controlled trials (RCTs) involving melanoma in the top ten highest dermatology journals by impact factor over the past four decades. Methods: A systematic review of RCTs involving melanoma within the top ten dermatology journals, as determined by impact factor, was conducted from inception to July 10th, 2023. Studies were included if they reviewed the diagnosis and/or treatment of melanoma, were RCTs, directly involved patients and were written in English. Studies were characterized as positive for reporting skin of color (SOC) if the demographic data in the results or methods sections included any of the following: race, ethnicity, skin of color, Fitzpatrick scale, sunburn tendency, phototype, skin type, or skin tone. Results: Out of 76 studies initially identified, only 49 articles met inclusion criteria. Of these 49 articles, only 24 articles recorded data of skin color from their demographics (49%). Subgroup analysis showed no statistically significant difference in the rate of reporting between studies grouped by decade (p = 0.779) or by study location (p = 0.763). Conclusion: Darker skin tones can disguise melanotic skin lesions. Less than 50% of RCTs related to melanoma in the top ten international dermatology journals included skin color within their results section to characterize study participants. This has a negative impact on our understanding of this potentially devastating disease. [ABSTRACT FROM AUTHOR]

Explosive pellets containing binary mixtures of 1,3,5-trinitro-1,3,5-triazine (RDX) and yacca resin "red gum" (RG) with composition ratios of 90:10, 95:5, and 98:2 RDX:RG were prepared. These were created without use of specialized pressing or casting facilities, making it a convenient formulation for researchers. Red gum, a component of molding powder, was mixed with RDX, both in powder form and in slurry format. The addition of red gum to RDX did not significantly change the sensitivity of RDX to impact or friction nor was thermal stability dramatically altered as judged by differential scanning calorimetry (DSC). Formulations of RDX:RG were pressed to produce pellets with densities ranging from 1.628-1.683 g/cm3. Pressed pellets were assembled in clear cellulose tubes to allow high speed camera photography to assess detonation velocity. Velocities between 8.04-8.50 km/s were determined. Photon Doppler velocimetry (PDV) measured CJ-pressures in the pellets between 24-29 GPa. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a progressive condition affecting more than 800 million individuals worldwide. Patient Reported Experience Measures (PREMs) are questionnaires aimed at evaluating patients' experiences with healthcare received. Given that CKD management often involves continuous treatments, capturing patient experiences can guide improvements in care that align with patients' preferences, making PREMS a relevant tool in CKD management. The Kidney PREM questionnaire was developed in the United Kingdom to measure patient experience across entire service provisions in patients with chronic kidney disease (CKD). This study aimed to adapt the English version to Spanish and Catalan and assess the face validity of the new language versions. Methods: The translation process was guided by the International Society of Pharmacoeconomics and Outcome Research (ISPOR) Principles of Good Practice for the Translation and Cultural Adaptation of Patient‑Reported Outcomes Measures and included forward and back translation, cognitive debriefing, and harmonisation between the Spanish and Catalan versions. Face validity was assessed in a sample of Spanish- and Catalan-speaking health professionals. Results: In the cognitive debriefing, 9 patients with CKD (4 in Catalan and 5 in Spanish) participated. Fourteen healthcare professionals (2 nurses and 12 nephrologists) assessed the face validity of the Catalan and Spanish versions. Overall, the language used in the original version of the questionnaire did not cause substantial problems for translation into Catalan or Spanish. Patients generally found the questionnaire to be relevant and relatively easy to complete but reported some difficulties with questionnaire design, including the use of 'skip' questions. Clinicians and nurses highly rated the questionnaire in terms of relevance (mean score of 8.7 on a 0–10 scale) and acceptability, indicating good face validity, but considered some elements to be lacking, such as the absence of an open-ended question or any queries regarding lifestyle. Conclusions: It was feasible to produce culturally adapted Spanish and Catalan versions of the Kidney PREM questionnaire, and they showed acceptable face validity. They will be useful tools for furthering research and clinical practice in CKD patients in Spain. [ABSTRACT FROM AUTHOR]

Objectives: Hearing loss is highly prevalent in older adults and is independently associated with accelerated cognitive decline. Cochlear implants are usually the only effective treatment for people with severe–profound hearing loss, who have the highest risk of cognitive decline and dementia, however, very few receive them. Current evidence of the effects of cochlear implant use on cognitive decline/dementia outcomes is limited and unclear. This study aimed to investigate the effect of cochlear implant use on longitudinal cognitive performance, as this intervention may be an effective method of modifying cognitive outcomes for older adults with significant hearing loss. Methods: This prospective longitudinal observational study investigated cognitive performance in a convenience sample of older adults (mean age 74 years) with cochlear implants over 4.5 years post-implantation, comparing this with that of community-living adults with untreated hearing loss/normal hearing over 3 years (Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing; AIBL). All participants were assessed at 18-month intervals from baseline using the same measures. Panel regression was used to compare cognitive trajectories. Results: Cochlear implant users demonstrated significantly improved performance in executive function and working memory, as well as stability in attention, psychomotor function, and visual learning at 4.5-year follow-up. Comparatively, AIBL participants showed significantly greater worsening performance per year in attention and psychomotor function, and stability in working memory and visual learning at 3-year follow-up. Conclusions: Cochlear implant use may delay cognitive decline and/or improve cognitive performance in older adults with severe–profound hearing loss, providing proof-of-concept evidence of the positive effects of hearing intervention on cognitive performance in older adults with hearing loss. [ABSTRACT FROM AUTHOR]

The explosive 2,4,6-trinitrophenol (picric acid) was prepared by five different methods using laboratory-grade chemicals as well as consumer-available chemicals in order to establish background forensic information. Nitrate sources were altered by using three concentrations of nitric acid or nitrate salts; an over-the-counter source of sulfuric acid was also investigated. Recovered products were identified using spectroscopic and thermal techniques. Impurities caused by over-the-counter starting materials were carried throughout the synthesis process to the crude recovered products and were detected by infrared and Raman spectroscopy and differential scanning calorimetry. In cases where nitrate salts were used; potassium picrate was recovered. [ABSTRACT FROM AUTHOR]

"Cancel culture" has become a prominent phrase in US political commentary, with supporters and opponents relying on different value-based arguments to express their views. At the same time, these camps often fall along predictable partisan political lines. What, then, are the real motivations for promoting and opposing behaviors sometimes labeled as "canceling" in contemporary American politics? We explore this question through survey data from Pew in 2020 and two original survey experiments, conducted on the 2021 CES and a 2023 online sample. We examine how Americans define the term "cancel culture," to what extent cancel culture is linked to both a range of core democratic values, and the role of partisanship in shaping support or opposition to specific behaviors. We observe a significant range of views about cancel culture and document connections to various political values. From our experiments, we find that partisanship is a potent driver of support for and understanding of cancel culture and that value-based framing has a weaker impact as compared to partisanship. Cancel culture provides an important case study of how Americans process conflicting norms and values, including free speech and political accountability, beyond the typical constraints of the formal political system. [ABSTRACT FROM AUTHOR]

The article "Assessment in the United States: Pathways Forward" discusses emerging assessment trends in higher education. The role of accreditation, program theory, and implementation fidelity, as well as student voice, are highlighted as crucial aspects of assessment. The authors emphasize the importance of involving students in the assessment process to create a more inclusive and effective educational environment. The article suggests that advancements in assessment can be supported by a dynamic accreditation system that encourages innovative practices in higher education. [Extracted from the article]

The editorial in Research in Drama Education acknowledges the legacy of John Somers, the founding editor, and reflects on the journal's history and future trajectory. It highlights the importance of inclusivity, scholarly debate, and international collaboration in the field of drama education. The current issue focuses on exploring racism, whiteness, and anti-blackness through applied theatre, featuring contributions from various countries and addressing social issues through drama and performance. The editorial team aims to continue fostering critical discussions and engaging with the evolving landscape of applied theatre. [Extracted from the article]

Severe wildfire may alter steep mountain streams by increasing peak discharges, elevating sediment and wood inputs into channels, and increasing susceptibility to landslides and debris flows. In the Pacific Northwest, where mean annual precipitation is high and mean fire‐return intervals range from decades to centuries, understanding of steep stream response to fire is limited. We evaluate the hydrologic and geomorphic response of ~100‐m‐long steep stream reaches to the large‐scale and severe 2020 fires in the Western Cascade Range, Oregon. In the two runoff seasons after the fires, peak flows in burned reaches were below the 2‐year recurrence interval flood, a level sufficient to mobilize the median grain size of bed material, but not large enough to mobilize coarser material and reorganize channel morphology. Sediment inputs to study streams consisted of two road‐fill failure landslides, slumps, sheetwash, and minor bank erosion; precipitation thresholds to trigger debris flows were not exceeded in our sites. There was a 50% increase in the number of large wood pieces in burned reaches after the fires. Changes in fluxes of water, sediment, and wood induced shifts in the balance of sediment supply to transport capacity, initiating a sequence of sediment aggradation and bed‐material fining followed by erosion and bed‐material coarsening. Gross channel form showed resilience to change, and an unburned reference reach exhibited little morphologic change. Post‐fire recruitment of large wood will likely have long‐term implications for channel morphology and habitat heterogeneity. Below‐average precipitation during the study period, combined with an absence of extreme precipitation events, was an important control on channel responses. Climate change may have a complex effect on stream response to wildfire by increasing the propensity for both drought and extreme rain events and by altering vegetation recovery patterns. [ABSTRACT FROM AUTHOR]

Limited literature has examined parents' unsolicited trait, mental state, and coping talk about media characters by race as they co‐view with their children. We observed 195 US parents describing an illustrated depiction of racialized social exclusion for their child (53% male; Mage = 5.46 years; 60% White) in their home setting. Families discussed a Black child being excluded by White children or a White child being excluded by Black children. Parents' victim, emotion, personality, and coping talk about the excluded child were coded. Parents were more likely to use victim talk (e.g., "she's being excluded") and emotion talk (e.g., "she's sad") when the excluded child was Black and were more likely to use personality talk (e.g., "she's shy") when the excluded child was White. We further explored parents' demographic, personal, and neighborhood correlates with their trait, mental state, and coping talk. White parents with greater levels of egalitarian attitudes used more victim talk and coping talk (e.g., "she should go play with them") about the White excluded child. Being more politically conservative was associated with White parents using more coping talk about the Black excluded child. White parents living in predominantly Black neighborhoods were less likely to use victim talk toward the Black child. BIPOC parents showed more nuanced patterns. These findings suggest that parents' unsolicited racial messaging varies by racial identification, sociodemographic characteristics, and neighborhood context. [ABSTRACT FROM AUTHOR]

Despite the growing variety of sequencing and variant-calling tools, no workflow performs equally well across the entire human genome. Understanding context-dependent performance is critical for enabling researchers, clinicians, and developers to make informed tradeoffs when selecting sequencing hardware and software. Here we describe a set of "stratifications," which are BED files that define distinct contexts throughout the genome. We define these for GRCh37/38 as well as the new T2T-CHM13 reference, adding many new hard-to-sequence regions which are critical for understanding performance as the field progresses. Specifically, we highlight the increase in hard-to-map and GC-rich stratifications in CHM13 relative to the previous references. We then compare the benchmarking performance with each reference and show the performance penalty brought about by these additional difficult regions in CHM13. Additionally, we demonstrate how the stratifications can track context-specific improvements over different platform iterations, using Oxford Nanopore Technologies as an example. The means to generate these stratifications are available as a snakemake pipeline at https://github.com/usnistgov/giab-stratifications. We anticipate this being useful in enabling precise risk-reward calculations when building sequencing pipelines for any of the commonly-used reference genomes. The GIAB genomic stratification resource defines challenging regions in three commonly used human genome references, including the first complete human genome (CHM13). These help understand strengths and weaknesses of sequencing and analysis methods. [ABSTRACT FROM AUTHOR]

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Equations for predicting body mass from stature and bi‐iliac (maximum pelvic) breadth have been developed, but have had variable success when applied to living or recently deceased individuals, calling into question their general applicability. Here we test these equations on a large, ethnically diverse sample. Skeletal and anthropometric data for 507 recently deceased Indigenous, Hispanic, and non‐Hispanic White adults were obtained from the New Mexico Decedent Image Database. The body mass of individuals with a "normal" body mass index (BMI = 18.5–24.9) is very accurately predicted, with an average directional bias of about 1% and an average random error of less than 8%. Underweight individuals (BMI < 18.5) are overpredicted, while overweight (BMI = 25–29.9) and especially obese (BMI≥30) individuals are underpredicted. Within BMI categories, there is a strong and isometric relationship between predicted and true body mass. Individual body mass prediction errors using the stature/bi‐iliac method are mainly dependent on variation in BMI. Because earlier humans were more likely to fall within or close to the normal BMI range, the equations should be applicable, on an individual basis, in archeological and paleontological contexts. Because of the prevalence of obesity in many modern populations, these equations are not applicable in a general forensic context. We derive new equations from nonobese individuals in our sample (n = 338), which produce reasonable average prediction errors. If obese individuals can be identified using other skeletal parameters, these equations may be useful in estimating body mass in nonobese forensic cases. [ABSTRACT FROM AUTHOR]

The contribution of age‐related structural brain changes to the well‐established link between aging and cognitive decline is not fully defined. While both age‐related regional brain atrophy and cognitive decline have been extensively studied, the specific mediating role of age‐related regional brain atrophy on cognitive functions is unclear. This study introduces an open‐source software tool with a graphical user interface that streamlines advanced whole‐brain mediation analyses, enabling researchers to systematically explore how the brain acts as a mediator in relationships between various behavioral and health outcomes. The tool is showcased by investigating regional brain volume as a mediator to determine the contribution of age‐related brain volume loss toward cognition in healthy aging. We analyzed regional brain volumes and cognitive testing data (Montreal Cognitive Assessment [MoCA]) from a cohort of 131 neurologically healthy adult participants (mean age 50 ± 20.8 years, range 20–79, 73% females) drawn from the Aging Brain Cohort Study at the University of South Carolina. Using our open‐source tool developed for evaluating brain‐behavior associations across the brain and optimized for exploring mediation effects, we conducted a series of mediation analyses using participant age as the predictor variable, total MoCA and MoCA subtest scores as the outcome variables, and regional brain volume as potential mediators. Age‐related atrophy within specific anatomical networks was found to mediate the relationship between age and cognition across multiple cognitive domains. Specifically, atrophy in bilateral frontal, parietal, and occipital areas, along with widespread subcortical regions mediated the effect of age on total MoCA scores. Various MoCA subscores were influenced by age through atrophy in distinct brain regions. These involved prefrontal regions, sensorimotor cortex, and parieto‐occipital areas for executive function subscores, prefrontal and temporo‐occipital regions, along with the caudate nucleus for attention and concentration subscores, frontal and parieto‐occipital areas, alongside connecting subcortical areas such as the optic tract for visuospatial subscores and frontoparietal areas for language subscores. Brain‐based mediation analysis offers a causal framework for evaluating the mediating role of brain structure on the relationship between age and cognition and provides a more nuanced understanding of cognitive aging than previously possible. By validating the applicability and effectiveness of this approach and making it openly available to the scientific community, we facilitate the exploration of causal mechanisms between variables mediated by the brain. [ABSTRACT FROM AUTHOR]

Generative Artificial Intelligence (GAI) represents an emerging field that promises the creation of synthetic data and outputs in different modalities. GAI has recently shown impressive results across a large spectrum of applications ranging from biology, medicine, education, legislation, computer science, and finance. As one strives for enhanced safety, efficiency, and sustainability, generative AI indeed emerges as a key differentiator and promises a paradigm shift in the field. This article explores the potential applications of generative AI and large language models in geoscience. The recent developments in the field of machine learning and deep learning have enabled the generative model's utility for tackling diverse prediction problems, simulation, and multi‐criteria decision‐making challenges related to geoscience and Earth system dynamics. This survey discusses several GAI models that have been used in geoscience comprising generative adversarial networks (GANs), physics‐informed neural networks (PINNs), and generative pre‐trained transformer (GPT)‐based structures. These tools have helped the geoscience community in several applications, including (but not limited to) data generation/augmentation, super‐resolution, panchromatic sharpening, haze removal, restoration, and land surface changing. Some challenges still remain, such as ensuring physical interpretation, nefarious use cases, and trustworthiness. Beyond that, GAI models show promises to the geoscience community, especially with the support to climate change, urban science, atmospheric science, marine science, and planetary science through their extraordinary ability to data‐driven modelling and uncertainty quantification. [ABSTRACT FROM AUTHOR]

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori–defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73–1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal. [ABSTRACT FROM AUTHOR]

Background: Biologic asthma therapies reduce exacerbations and long‐term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real‐world population of adults with severe asthma. Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow‐up were grouped into those who did, or did not, initiate biologics (anti‐IgE, anti‐IL5/IL5R, anti‐IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super‐response criteria were: FEV1 increase by ≥500 mL, new well‐controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non‐initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super‐responses. Responses/super‐responses were more frequent in biologic initiators than in non‐initiators; nevertheless, ~40–50% of initiators did not meet response criteria. Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non‐initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super‐responses in all outcome domains, 40–50% did not meet the response criteria. [ABSTRACT FROM AUTHOR]

The advantage of Universal Design (UD) over mere barrier-free design is that it can benefit everyone, regardless of age or ability. The imperative to include design for personal safety even outranks accessibility as a design precept. Evolved almost four decades ago, Ron Mace's Seven Principles did not anticipate advanced standards of safety in today's world. Whilst Principle Five - 'Tolerance for Error', states that 'the design minimizes hazards and the adverse consequences of accidental or unintended actions', this notion of 'error' implies that it is the user who is at fault, rather than the provider. This may lead to inhibition and fear, hampering one's lifestyle in a multitude of ways. Fear of falling, inhibition of being unable to find a public toilet, forgetting a password or simply being made to feel old and incapable can all have an adverse effect. A cross-disciplinary group of experts undertook a number of studies on design for age-friendly cities in Ireland, through empirical research, experiential exercises and dissemination into third-level design education. Studies on design and facilities that lead to an individual's lack of confidence are discussed, including a research programme undertaken for the National Disability Authority on the Universal Design of Fall Detection Technologies. The paper proposes that an additional Principle: "Reduction of Fear" should be a basic design parameter in all aspects of the built environment as well as IT and services. By broadening its scope and joining forces with health and safety issues, UD becomes more inclusive, desirable to client bodies and attractive to everyone. The paper identifies areas where improvement in design is urgently required, suggesting the breadth of benefits accruing from more inclusive design, particularly in reducing fear through safer home zone environments. [ABSTRACT FROM AUTHOR]

Background: Depression is common in people with chronic kidney disease, yet little is known about how depression is identified and managed as part of routine kidney care. Objectives: The primary objective was to survey all UK adult kidney centres to understand how depression is identified and managed. A secondary objective was to broadly describe the variability in psychosocial care. Design: Online survey. Methods: The survey comprised of three sections: (1) general kidney care, (2) psychological provision and (3) social work provision. Results: 48/68 (71%) of centres responded to the general survey with 20 and 13 responses from psychological and social work module respectively. Only 31.4% reported having both in centre psychological and social work practitioners. Three centres reported no access to psychosocial provision. Of the 25 centres who reported on pathways, 36.0% reported having internal pathways for the identification and management of depression. Within services with psychological provision, screening for depression varied across modality/group (e.g., 7.1% in mild/moderate chronic kidney disease vs. 62.5% in kidney donors). Cognitive Behavioural Therapy and Acceptance and Commitment Therapy were the most common interventions offered. Most psychosocial services were aware of the National Institute for Health and Care Excellence guidelines for managing depression in long‐term conditions (n = 18, 94.7%) yet few fully utilised (n = 6, 33.3%). Limited workforce capacity was evident. Conclusions: There is considerable variability in approaches taken to identify and treat depression across UK kidney services, with few services having specific pathways designed to detect and manage depression. Workforce capacity remains a significant issue. [ABSTRACT FROM AUTHOR]

Aims: There is a need to increase representation of diverse older adults in health‐related qualitative research to better understand and improve chronic disease care over the lifespan. Our aim was to elicit perspectives about research recruitment among a diverse sample of older adults with diabetes participating in a qualitative study. Methods: Older adults with diabetes and caregivers were recruited through purposive sampling for semi‐structured interviews focused on diabetes self care. Six questions were used to explore recruitment strategies and recommendations for engaging older adults in research. We analysed interview transcripts using descriptive analysis to identify themes related to engaging older adults in research studies. Results: Seventeen older adults with diabetes and three caregivers participated (N = 20). Descriptive analysis revealed four themes: (1) Recruitment of older adults requires varied strategies to overcome barriers to engagement and participation; (2) Building and leveraging personal relationships is central to successful recruitment; (3) Transparent communication about the research process and value of the study is needed to inform and motivate older adults to participate; and (4) Research offers a connection to a broader community: sharing, learning and helping others. Conclusions: We found four main themes related to the complexity of recruiting older adults for research studies. These insights may inform more effective, equitable and inclusive recruitment efforts targeted at older adults in the future. [ABSTRACT FROM AUTHOR]

From October 2024 when the Worker Protection (Amendment of Equality Act 2010) Act 2023 comes into force, employers will be required to comply with a new duty to take reasonable steps to prevent sexual harassment of their employees. Under the Act, an employment tribunal will have the power to increase compensation by up to 25% if it finds that an employer has breached this duty. The Act started out as a private members bill and, in its original form, the bill contained a provision to extend protection against workplace harassment perpetuated by a third party such as a customer, client or visitor. However, following a difficult passage through Parliament, this provision was removed, and other proposed protections watered down. The reasons for this are explored in the following analysis which reveals the prioritisation of freedom of speech concerns over an improved legal regime for protecting workers against sexual harassment. The paper concludes by considering the Act's likely impact and what further protections are needed in this area. [ABSTRACT FROM AUTHOR]

Outbreaks of insects and diseases are part of the natural disturbance regime of all forests. However, introduced pathogens have had outsized impacts on many dominant forest tree species over the past century. Mitigating these impacts and restoring these species are dilemmas of the modern era. Here, we review the ecological and economic impact of introduced pathogens, focusing on examples in North America. We then synthesize the successes and challenges of past biotechnological approaches and discuss the integration of genomics and biotechnology to help mitigate the effects of past and future pathogen invasions. These questions are considered in the context of the transgenic American chestnut, which is the most comprehensive example to date of how biotechnological tools have been used to address the impacts of introduced pathogens on naïve forest ecosystems. [ABSTRACT FROM AUTHOR]

Aedes aegypti mosquitoes are major vectors of dengue, chikungunya, and other arboviral diseases. Ae. aegypti's capacity to reproduce and to spread disease depends on the female mosquitoes' ability to obtain blood meals and find water-filled containers in which to lay eggs (oviposit). While humidity sensation (hygrosensation) has been implicated in these behaviors, the specific hygrosensory pathways involved have been unclear. Here, we establish the distinct molecular requirements and anatomical locations of Ae. aegypti Dry Cells and Moist Cells and examine their contributions to behavior. We show that Dry Cell and Moist Cell responses to humidity involve different ionotropic receptor (IR) family sensory receptors, with dry air-activated Dry Cells reliant upon the IR Ir40α, and humid air-activated Moist Cells upon Ir68a. Both classes of hygrosensors innervate multiple antennal sensilla, including sensilla ampullacea near the antennal base as well as two classes of coeloconic sensilla near the tip. Dry Cells and Moist Cells each support behaviors linked to mosquito reproduction but contribute differently: Ir40α-dependent Dry Cells act in parallel with Ir68α-dependent Moist Cells to promote blood feeding, while oviposition site seeking is driven specifically by Ir68α-dependent Moist Cells. Together these findings reveal the importance of distinct hygrosensory pathways in blood feeding and oviposition site seeking and suggest Ir40α-dependent Dry Cells and Ir68α-dependent Moist Cells as potential targets for vector control strategies. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most prominent tumor type among women, accounting for 32% of newly diagnosed cancer cases. BC risk factors include inherited germline pathogenic gene variants and family history of disease. However, the etiology of the disease remains occult in most cases. Therefore, in the absence of high-risk factors, a polygenic basis has been suggested to contribute to susceptibility. This information is utilized to calculate the Polygenic Risk Score (PRS) which is indicative of BC risk. This study aimed to evaluate retrospectively the clinical usefulness of PRS integration in BC risk calculation, utilizing a group of patients who have already been diagnosed with BC. The study comprised 105 breast cancer patients with hereditary genetic analysis results obtained by NGS. The selection included all testing results: high-risk gene-positive, intermediate/low-risk gene-positive, and negative. PRS results were obtained from an external laboratory (Allelica). PRS-based BC risk was computed both with and without considering additional risk factors, including gene status and family history. A significantly different PRS percentile distribution consistent with higher BC risk was observed in our cohort compared to the general population. Higher PRS-based BC risks were detected in younger patients and in those with FH of cancers. Among patients with a pathogenic germline variant detected, reduced PRS values were observed, while the BC risk was mainly determined by a monogenic etiology. Upon comprehensive analysis encompassing FH, gene status, and PRS, it was determined that 41.90% (44/105) of the patients demonstrated an elevated susceptibility for BC. Moreover, 63.63% of the patients with FH of BC and without an inherited pathogenic genetic variant detected showed increased BC risk by incorporating the PRS result. Our results indicate a major utility of PRS calculation in women with FH in the absence of a monogenic etiology detected by NGS. By combining high-risk strategies, such as inherited disease analysis, with low-risk screening strategies, such as FH and PRS, breast cancer risk stratification can be improved. This would facilitate the development of more effective preventive measures and optimize the allocation of healthcare resources. [ABSTRACT FROM AUTHOR]

Background: Over 35 million falls occur in older adults annually and are associated with increased emergency department (ED) revisits and 1‐year mortality. Despite associations between medications and falls, the prevalence of fall risk‐increasing drugs remains high. Our objective was to implement an ED‐based medication reconciliation for patients presenting after falls and determine whether an intervention targeting high‐risk medications was related to decreased future falls. Methods: This was an observational prospective cohort study at a single site in the United States. Adults 65 years and older presenting to the ED after falls had a pharmacist review their medicines. Pharmacists made recommendations to taper, stop, or discuss medications with the primary clinician. At 3, 6, and 12 months, we recorded the number of fall‐related return ED visits and determined if recommended medication changes had been implemented. We compared the rate of return visits of patients who had followed the medication change recommendations and those who received recommendations but had no change in their medications using chi‐square tests. Results: A total of 577 patients (mean age 81 years, 63.6% female) were enrolled of 1509 potentially eligible patients. High‐risk medications were identified in 310 patients (53.7%) who received medication recommendations. High‐risk medications were associated with repeat fall‐related visits at 12 months (risk difference 8.1% [95% confidence interval 0.97–15.0]). A total of 134 (43%) patients on high‐risk medications had evidence of medication modification. At 12 months, there was no statistically significant difference in return fall visits between patients who had modifications to medications compared with those who had not implemented changes (p = 0.551). Conclusions: Our findings identified opportunities for medication optimization in over half of emergency visits for falls and demonstrated that medication counseling in the ED is feasible. However, evaluation of the effect on future falls was limited. [ABSTRACT FROM AUTHOR]

This essay examines strategies for thoughtfully integrating generative AI (Gen-AI) into management curricula to enhance student learning while mitigating risks like overreliance. We make the case that outright resistance is counterproductive; instead, management educators should embrace Gen-AI's potential to create more engaging, experiential learning aligned with andragogical principles. We provide a conceptual framework mapping nine Gen-AI objectives to the principles of andragogy. A semester-long course example illustrates this framework in action through AI activities fostering autonomy, competence, and real-world application. Student surveys revealed overwhelmingly positive perceptions of Gen-AI integration and improved exam scores. However, dependence risks remain. The essay discusses strategies to enhance critical thinking, personal growth, and academic integrity. Overall, we propose that prudent Gen-AI adoption can enrich management education, but long-term vigilance regarding overreliance is vital. [ABSTRACT FROM AUTHOR]

Individual, biological, psychological, and social factors have each been associated with sexual satisfaction. In the current study we examine ways that these factors combined in the same study might be associated with understanding couples' sexual satisfaction and harmonious sexual passion by evaluating an actor-partner-interdependence-model (APIM). This model was based on data (N = 2,187 couples) collected as part of a nationally representative study of the Couple Relationships and Transition Experiences (CREATE) study. Structural equation modeling was used to assess the APIM model. The results indicated that the quality of sleep and the number of physical symptoms both partners were experiencing were substantially associated with the same individual's depression and anxiety. In turn, depression and anxiety were associated with the quality of communication and the ability to resolve conflict. These social variables had strong associations with sexual satisfaction and they, along with sexual satisfaction, were significantly associated with the couple's ability to experience harmonious sexual passion in their relationship. We examined how couples' sleep, symptoms of illness, depression and anxiety, communication and conflict were associated with couples' sexuality. With a sample of 2,187 couples, we found that sleep and symptoms of illness were associated with depression and anxiety which were associated with communication and conflict. Communication and conflict had strong associations with sexual satisfaction and harmonious sexual passion. [ABSTRACT FROM AUTHOR]

Headwater streams are reliant on riparian tree leaf litterfall to fuel brown food webs. Terrestrial agents like herbivores and contaminants can alter plant growth, litter production, litter quality, and the timing of litterfall into streams, influencing aspects of the brown food web. At Mount St. Helens (USA), early successional streams are developing willow (Salix sitchensis) riparian zones. The willows are attacked by stem-boring herbivores, altering litter quality and the timing of litterfall. Within a established experimental plots, willows (male and female plants) were protected from herbivores using insecticides and provided with experimental additions of nitrogen. This enabled us to test the interacting influences of herbivores, nitrogen deposition, and willow sex on leaf litter quality, aquatic litter decomposition, and microbial and invertebrate detritivores. We found weak litter quality effects (higher N and lower C:N) for the herbivore treatment, but no effect of nitrogen deposition. Although litter decomposition rates were not strongly affected by litter treatments, detritivore communities were altered by all treatments. Nitrogen deposition resulted in decreased bacterial richness and decreased fungal diversity in-stream. Aquatic macroinvertebrate communities were influenced by the interacting effects of herbivory and nitrogen addition, with abundances highest in herbivore litter with the greatest N addition. Shredders showed the highest abundance in male, herbivore-attacked litter. The establishment of riparian willows along early successional streams and their interacting effects with herbivores and nitrogen deposition may be influencing detritivore community assembly at Mount St. Helens. More broadly, global changes like increased wet and dry N deposition and expanded ranges of key herbivores might influence tree litter decomposition in many ecosystems. [ABSTRACT FROM AUTHOR]

Residential schools are commonly used in India to provide education for Indigenous youth, which requires young people to stay for long periods at distance from their families and communities. Internationally, there is clear evidence for the deleterious effects of residential schools on the mental health and social and community outcomes of Indigenous children, however little is known about the Indian Indigenous experience. This study examined the impact of residential schooling on Indigenous children's wellbeing and that of their communities, using data from an ethnographic research project in Attapadi, Kerala, including interviews, focus group discussions and participant observation with Indigenous communities. Key outcomes from residential schooling reported by the participants include the fear of losing Indigenous identity, shame of being Indigenous, change in the attitude of young people when they returned from schools, and feelings of confusion and stress that young Indigenous participants felt trying to fit into their communities on their return. Findings suggest that these Indigenous youth felt disconnected from several factors that are known to promote resilience for Indigenous communities including a strong cultural identity, connection to the land and ancestors, thereby making them more vulnerable to poor mental health and negative impacts on their overall wellbeing. Addressing these concerns requires a detailed understanding of the specific factors influencing outcomes for Indigenous youth within the Indian residential schooling system, and designing and implementing data-informed conceptual, structural and policy change including the provision of culturally safe mental health services. [ABSTRACT FROM AUTHOR]

Background: Lead exposure at any concentration can adversely impact health, with children being more vulnerable to its effects. In England, children with an elevated blood lead concentration (BLC) are reported to Health Protection Teams (HPTs) for public health investigation. A detailed review of these cases has not yet been conducted. Objectives: The objectives of this study were to describe the demographics, likely setting and sources of lead exposure, risk behaviours, public health investigations and outcomes for children aged <16 years with a BLC requiring public health action reported to HPTs between 2014–2022 in England. Methods: Data were collected via a lookback questionnaire and a live enhanced surveillance questionnaire. Data were deduplicated, cleaned and results summarised as numbers and percentages using R studio. A thematic analysis was conducted on qualitative responses to a question relating to problems experienced during case investigation. Results: There were 340 cases in our study: the majority were aged 1–4 years old (53%) and male (69%). Ethnicity data was poorly recorded. A higher than expected proportion (31%) lived in the most deprived areas. Pica (76%) and learning difficulties (60%) were often present. Cases were primarily exposed to lead in the domestic setting (92%) with paint (43%) and soil (29%) the most common exposures. Most cases lived in rented accommodation (63%), with a higher proportion in social rentals (48%) than privately rented (37%). Case investigations were resource intensive and poor stakeholder engagement/response was most frequently identified as challenging by HPTs. Conclusions: Lead exposure is harmful to children and requires public health and clinical management, which can be complex and challenging. Prevention of lead exposure in children should be the focus of intervention efforts. Outreach, engagement and preventative work should focus on both renters and homeowners. Collecting ethnicity data consistently may enable identification of more specific groups at increased risk of lead exposure in England. [ABSTRACT FROM AUTHOR]

Purpose: Precision Prostatectomy (PP) is a viable treatment option for men with unilateral dominant cancer who are interested in preserving functional outcomes. To date, the data published about the outcomes of this technique has come from a single center only (Henry Ford - HF). We present the surgical, functional, and oncological outcomes of the first series of patients to undergo PP outside of HF, to demonstrate the safety and reproducibility of the technique. Methods: Between 2022 and 2023, PP was offered to select patients who were interested in preserving their functional status. Men who underwent PP were followed at 3 monthly intervals; information regarding their functional status was simultaneously obtained. Men who had biochemical recurrence were advised to undergo remnant biopsy. If residual cancer was detected, then remnant removal was performed. Results: The median age and median PSA of the study group was 63 years and 6.89 ng/ml respectively. The median operative and console times were 196.5 and 154 minutes. No intra-operative complications were noted. Three patients had a total of three post-operative complications. Three patients had biochemical recurrence; cancer was not detected in any of these patients on postoperative biopsies of the prostatic remnant. At 12 months, 91% of patients reported using 0 pads/day and 90.9% of pre-operatively potent patients were potent at 12 months. Conclusion: PP is a safe and reproducible technique that can ensure cancer control and preservation of functional status in select patients. Further studies with large sample sizes and longer follow-up are required to ascertain the long-term outcomes of this surgical technique. [ABSTRACT FROM AUTHOR]

Objectives: Comparisons between Indigenous peoples over time and within a particular geographic region can shed light on the impact of environmental transitions on the skeleton, including relative bone strength, sexual dimorphism, and age‐related changes. Here we compare long bone structural properties of the inhabitants of the late prehistoric‐early historic Pecos Pueblo with those of present‐day Indigenous individuals from New Mexico. Materials and Methods: Femora and tibiae of 126 adults from Pecos Pueblo and 226 present‐day adults were included in the study. Cross‐sectional diaphyseal properties—areas and second moments of area—were obtained from past studies of the Pecos Pueblo skeletal sample, and from computed tomography scans of recently deceased individuals in the present‐day sample. Results: Femora and tibiae from Pecos individuals are stronger relative to body size than those of present‐day Indigenous individuals. Present‐day individuals are taller but not wider, and this body shape difference affects cross‐sectional shape, more strongly proximally. The tibia shows anteroposterior strengthening among Pecos individuals, especially among males. Sexual dimorphism in midshaft bone shape is stronger within the Pecos Pueblo sample. With aging, Pecos individuals show more medullary expansion but also more subperiosteal expansion than present‐day individuals, maintaining bone strength despite cortical thinning. Discussion: Higher activity levels, carried out over rough terrain and throughout adult life, likely explain the relatively stronger lower limb bones of the Pecos individuals, as well as their greater subperiosteal expansion with aging. Greater sexual dimorphism in bone structure among Pecos individuals potentially reflects greater gender‐based differences in behavioral patterns. [ABSTRACT FROM AUTHOR]

Urbanization and expanding road networks threaten some avian populations through habitat loss and degradation. Barn owls (Tyto alba) have been particularly affected through roadway mortality, loss of grassland, and conversion or destruction of nesting sites. To combat declines and bolster reproduction, and as part of integrated pest management to reduce crop damage, some land managers provide supplemental owl nesting sites via the installation of nest boxes. If nearby habitat and land cover characteristics are not considered when placing boxes, such as major roads or other anthropogenic features, owls could be attracted to locations that could hinder populations further. We investigated the effects of roads and urban areas on barn owl breeding occupancy and productivity to provide information to help guide the placement of nest boxes. We monitored >300 nest boxes over the 2020 and 2021 breeding seasons in southwestern Idaho, USA, where substantial roadway mortality of barn owls occurs. Barn owls occupied >60% of nest boxes, but the likelihood of breeding occupancy decreased with increasing proximity of nest boxes to roads. Boxes 500 m from roads had a predicted probability of occupancy of over 0.9, which was nearly double that of boxes within 100 m. Proximity to roads also was associated with reduced productivity such that boxes within 100 m of roads were predicted to produce approximately 1 fewer fledgling than those 500 m away. There was no evidence that the proportion of urban area surrounding nest boxes substantially influenced breeding occupancy or productivity. Thus, land managers can consider placing nest boxes for barn owls farther from roads when possible as a potential tactic to increase the probability of breeding occupancy and to foster higher productivity. [ABSTRACT FROM AUTHOR]

Exacerbation frequency strongly influences treatment choices in patients with severe asthma. What is the extent of the variability of exacerbation rate across countries and its implications in disease management? We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Stereotypes of the two parties play an important role in political cognition, and a range of recent studies have examined the content and effects of partisan stereotypes. However, little work has studied change in partisan stereotypes over time. We address this question by comparing data on stereotypes of partisans collected before and after the Trump presidency, a time when we might expect individuals' images of the two parties to undergo significant change. Using a structural topic model, we compare responses to open-ended questions asking respondents to list words describing members of the two parties from 2016 and 2021. We find that partisan stereotypes in the 2021 sample are less group- and issue-based and focused more on personal traits. These results suggest that, during the Trump era, members of the mass public came to see the parties in more personalized, character-focused terms, potentially contributing to affective polarization. [ABSTRACT FROM AUTHOR]

Public response to risk often over- or under-estimates risk because individuals and social processes interact. This paper applies agent-based modelling to understand public risk perception in response to product recall through a risk model that forms the basis of a risk assessment procedure. We model collective response to risks associated with the consumption of contaminated or defective products in the context of product recalls during contamination scandals such as the cases of contaminated milk products in China. The main contribution is that we demonstrate how agent-based modelling can be used to study social risk amplification in a product contamination crisis. The main innovation of our model is that it integrates an event discovery step – in which risk perceivers assimilate risk through the risk beliefs of others, direct experience, and product recall decisions – with a recreancy assessment step – in which risk perceivers make judgments about wrongfulness. We show how the model can be calibrated with a consumer survey and validated. Finally, we demonstrate how to use the model for assessing and managing risk in organizational crises of a similar nature. [ABSTRACT FROM AUTHOR]

We describe a case of culture-negative infective endocarditis due to Neisseria gonorrhoeae, where the application of metagenomics shotgun sequencing in blood played a pivotal role in elucidating the underlying aetiology, guiding targeted therapy and ultimately resulting in the patient’s complete recovery. Beyond its immediate clinical impact, prompt treatment bears significant implications for public health. The utilisation of molecular testing emerges as a valuable strategy to enhance diagnostic accuracy, particularly in cases involving fastidious organisms that are infrequently associated with infective endocarditis. [ABSTRACT FROM AUTHOR]

OBJECTIVE We characterized the receipt of diabetes specialty care and management services among older adults with diabetes. RESEARCH DESIGN AND METHODS Using a 20% random sample of fee-for-service Medicare beneficiaries aged ≥65 years, we analyzed cohorts of type 1 diabetes (T1D) or type 2 diabetes (T2D) with history of severe hypoglycemia (HoH), and all other T2D annually from 2015 to 2019. Outcomes were receipt of office-based endocrinology care, diabetes education, outpatient diabetes health services, excluding those provided in primary care, and any of the aforementioned services. RESULTS In the T1D cohort, receipt of endocrinology care and any service increased from 25.9% and 29.2% in 2015 to 32.7% and 37.4% in 2019, respectively. In the T2D with HoH cohort, receipt of endocrinology care and any service was 13.9% and 16.4% in 2015, with minimal increases. Age, race/ethnicity, residential setting, and income were associated with receiving care. CONCLUSIONS These findings suggest that many older adults may not receive specialty diabetes care and underscore health disparities. [ABSTRACT FROM AUTHOR]

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior. Individuals with stroke aphasia have premature brain aging in intact regions of the lesioned hemisphere. In left domain-general areas, premature brain aging significantly predicts aphasia severity, suggesting that isolate aging matters for behavior. [ABSTRACT FROM AUTHOR]

Despite evidence showing rising suicidality among lesbian, gay, and bisexual (LGB) and Black adolescents, separately, there is scant research on suicide risk trajectories among youth groups across both racial and sexual identities. Thus, we examined trajectories of self-reported suicidal ideation and attempt and their associations with bullying among New York City-based adolescents. We analyzed 2009–2019 NYC Youth Risk Behavior Survey data. We ran weighted descriptive and logistic regression analyses to test for trends in dichotomous suicidal ideation, suicide attempt, bullying at school, and e-bullying variables among students across both race/ethnicity and sexual identity. We assessed associations between suicidality trends and bullying with logistic regressions. Models controlled for age and sex. Suicidal ideation and attempt were 2 and 5 times more likely among LGB than heterosexual participants, respectively. Bullying at school and e-bullying were 2 times more likely among LGB than heterosexual participants. Black LGB participants were the only LGB group for which both suicidal ideation (AOR = 1.04, SE =.003, p <.001) and attempt (AOR = 1.04, SE =.004, p <.001) increased over time. Both increased at accelerating rates. Conversely, White LGB participants were the only LGB group for which both suicidal ideation (AOR = 0.98, SE =.006, p <.001) and attempt (AOR = 0.92, SE =.008, p <.001) decreased over time. These changes occurred in parallel with significant bullying increases for Black and Latina/o/x LGB adolescents and significant bullying decreases for White LGB adolescents. Bullying was positively associated with suicidal ideation and attempt for all adolescents. Findings suggest resources aimed at curbing rising adolescent suicide should be focused on Black LGB youth. [ABSTRACT FROM AUTHOR]

This study explores the impact of appearance and speech on human perceptions of faces in human- robot interactions. Three videos were generated depicting the real face of an artist and two virtual versions of the same artist, with increasing resolution and fidelity. Each video was presented with and without speech, with matching levels of fidelity to the faces (real human speech and machine- generated speech of two levels of realism). Participants viewed all six videos and rated them on measures such as convincing, trustworthy, realistic, likable, showed biological movement, reassuring, friendly, familiar, and humanness. We found that the inclusion of speech (real) had a significant positive impact on the impression formation of real human appearance. In contrast, perceptions of the virtual avatars were more negative when speech (machine-like) was incorporated. This study illustrates the differential effects that speech can have on virtual faces in interactive settings. [ABSTRACT FROM AUTHOR]

Presbycusis is one of the most prevalent disabilities in aged populations of industrialized countries. As we age less excitation reaches the central auditory system from the periphery. To compensate, the central auditory system [e.g., the inferior colliculus (IC)], downregulates GABAergic inhibition to maintain homeostatic balance. However, the continued downregulation of GABA in the IC causes a disruption in temporal precision related to presbycusis. Many studies of age-related changes to neurotransmission in the IC have therefore focused on GABAergic systems. However, we have discovered that dense core vesicles (DCVs) are significantly upregulated with age in the IC. DCVs can carry neuropeptides, co-transmitters, neurotrophic factors, and proteins destined for the presynaptic zone to participate in synaptogenesis. We used immuno transmission electron microscopy across four age groups (3-month; 19-month; 24-month; and 28-month) of Fisher Brown Norway rats to examine the ultrastructure of DCVs in the IC. Tissue was stained post-embedding for GABA immunoreactivity. DCVs were characterized by diameter and by the neurochemical profile (GABAergic/non-GABAergic) of their location (bouton, axon, soma, and dendrite). Our data was collected across the dorsolateral to ventromedial axis of the central IC. After quantification, we had three primary findings. First, the age-related increase of DCVs occurred most robustly in non-GABAergic dendrites in the middle and low frequency regions of the central IC during middle age. Second, the likelihood of a bouton having more than one DCV increased with age. Lastly, although there was an agerelated loss of terminals throughout the IC, the proportion of terminals that contained at least one DCV did not decline. We interpret this finding to mean that terminals carrying proteins packaged in DCVs are spared with age. Several recent studies have demonstrated a role for neuropeptides in the IC in defining cell types and regulating inhibitory and excitatory neurotransmission. Given the age-related increase of DCVs in the IC, it will be critical that future studies determine whether (1) specific neuropeptides are altered with age in the IC and (2) if these neuropeptides contribute to the loss of inhibition and/or increase of excitability that occurs during presbycusis and tinnitus. [ABSTRACT FROM AUTHOR]

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher prebiologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.39; p=0.001) post-biologic for anti-IL5/5R. Prebiologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R²: 0.751), compared to BEC (adjusted R²: 0.747) or FeNO alone (adjusted R²: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline. [ABSTRACT FROM AUTHOR]