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Objective: Advanced‐stage laryngeal squamous cell carcinoma is treated with primary surgery or chemoradiation. We aim to determine if there are differences in postoperative functional oral intake in primary (PL) versus salvage laryngectomees (SL). Study Design: Retrospective cohort study. Setting: Patients who underwent laryngectomy between 2011 and 2021. Methods: We examined demographic, diagnostic, treatment, and swallow function data pre‐ and postoperatively. A follow‐up survey was distributed to assess current swallow status. Results: One hundred twenty‐five patients were included. Preoperatively, 68.8% of patients reported dysphagia. Median functional oral intake score (FOIS) was 4.0 [interquartile range, IQR: 1.0‐6.75]. The SL group had lower preop FOIS [2.0; IQR: 1.0‐4.75] that did not reach significance compared to the PL group [4.5; IQR: 1.0‐7.0] (P =.052). 73.4% of patients had a feeding tube. The PL group was more likely to have the tube removed [odds ratio, OR: 2.4; confidence interval, CI: 1.0‐5.7]. The SL group was more likely to require feeding tube placement more than 6 months postop [OR: 6.9; CI: 1.65‐32.6]. SL FOIS scores improved by 3 months postop to 5 (SL ΔFOIS = 3, P =.0150). PL scores improved to 7 [PL ΔFOIS = 2, P =.0005] at 12 to 15 months. Sixty‐nine patients were contacted for a follow‐up survey and 16 completed this survey. 30.4% patients reported dietary restrictions (mean 4.4 years postop). Conclusion: Patients undergoing SL appear to obtain similar swallow outcomes compared to PL at 3 to 6 months postlaryngectomy, but plateau. The PL group continues to improve up to 1 year postoperatively. Fifty percent of patients report on‐going dysphagia after 5 years. [ABSTRACT FROM AUTHOR]

Animals adjust their habitat use patterns in response to changes in their physiological needs and environmental conditions. Understanding the mechanisms underlying resource selection and space use across time and space reveals effects of the environment on animals' decisions. We explored the effects of habitat availability and heterogeneity on the seasonal and annual space use and resource selection of two free‐roaming feral burro (Equus asinus) populations in the United States within distinct climate and habitat conditions: the Sonoran Desert and the Colorado Plateau. As an introduced yet protected species in the United States, understanding burros' interactions with habitat elements is important for their conservation and management, as well as the conservation of sympatric wildlife. We used GPS locations of female burros (72 animals across both study areas) to delineate annual and seasonal ranges and resource selection patterns. We evaluated effects of mean and CV of habitat covariates, including forage, distance to water, and topography, representing availability and heterogeneity of resources, on seasonal and annual range size of burros. Moreover, we explored how burro seasonal and annual resource selection patterns were affected by availability and heterogeneity of resources. In the Sonoran Desert study area, burros had smaller seasonal and annual ranges and constant resource selection patterns across a year, likely due to a freshwater lake in the area, making water a nonlimiting resource. Human presence was the greatest factor affecting range size and resource selection in the Sonoran Desert, where burros selected for areas near roads and human recreation. In the Colorado Plateau study area, where resources were more seasonal, we found larger range sizes and fluctuating resource selection patterns compared to the Sonoran Desert population. Spatial variation in forage, water, and topography significantly affected range size of burros inhabiting the Colorado Plateau study area. Productive habitats with available water support smaller ranges and a more consistent pattern of resource selection. Our results highlight the positive effect of habitat heterogeneity and the negative effect of habitat productivity on range size of animals. Our findings contribute to an improved understanding of habitat requirements for free‐roaming burros that currently live under various climate and habitat conditions globally. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Skilled nursing facilities (SNFs) are an ideal setting to implement the Age‐Friendly Health System (AFHS) approach, an initiative by the Institute for Healthcare Improvement (IHI) centered on the 4Ms: what matters, mobility, mentation, and medication. AFHS implementation has not been well studied in SNFs.A 112‐bed VA SNF implemented a facility‐wide AFHS initiative including the following: (1) participating in a national IHI Age‐Friendly Action Community; (2) establishing an AFHS workgroup centered on the 4Ms; (3) identifying meaningful clinical tools and frameworks for capturing each M; and (4) developing sustainment methods. Clinical (life‐sustaining treatment, falls, disruptive behaviors, and medication deprescribing) and quality outcomes (rehospitalization, emergency department utilization, and discharge to the community) in addition to patient satisfaction were compared pre‐ and post‐AFHS implementation (bed days of care [BDOC] 17413) to post‐implementation (BDOC 20880).Clinical outcomes demonstrated improvements in the 4Ms, including: (1) what matters: 14% increase in life‐sustaining treatment documentation (82%–96%; p < 0.01); (2) mobility: reduction in fall rate by 34% (8.15 falls/1000 BDOC to 5.41; p < 0.01); (3) mentation: decrease in disruptive behavior reporting system (DBRS) by 62% (5.11 DBRS/1000 BDOC to 1.96; p = 0.04); (4) medications: 53% increase in average potentially inappropriate medications (PIMs) deprescribing (0.38–0.80 interventions/patient; p < 0.01). Quality outcomes improved including rehospitalization (25.6%–17.9%) and emergency department utilization (5.3%–2.8%) within 30 days of admission. Patient satisfaction scores improved from a mean of 77.2 (n = 31, scale 1–100) to 81.3 (n = 42).Implementation of the AFHS initiative in a SNF was associated with improved clinical and quality outcomes and patient satisfaction. We describe here a sustainable, interprofessional approach to implementing the AFHS in a SNF. [ABSTRACT FROM AUTHOR]

Children under‐5 years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross‐sectional study comprised a household survey with samples of child food (n = 382) and structured observations of food preparation (n = 197) among children aged 6–59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in South Sudan. We quantified Escherichia coli and total coliforms (TCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% (n = 164) of samples were contaminated with E. coli (43% >0 E. coli CFU/g, 95% CI 38%–48%), and 90% (n = 343) had >10 TCs (CFU/g) (>10 TC CFU/g, 95% CI 87%–93%). Risk factors associated (p < 0.05) with child food contamination included if the child fed themselves (9.05 RR, 95% CI [3.18, 31.16]) and exposure to animals (2.63 RR, 95% CI [1.33, 5.34]). This study highlights the risk factors and potential control strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to enteric pathogens. Key messages: Food is a potentially important pathway for enteric disease transmission and a major concern for children recovered from severe acute malnutrition (SAM) in humanitarian settings.In low‐income South Sudan, 43% (n = 164) of child food samples from households with a child at risk of relapse to SAM were contaminated with Escherichia coli and 90% (n = 343) with total coliforms (TCs).Child self‐feeding and animal presence in the household were identified as key risk factors for food contamination.Future research should assess the relative importance of the identified critical control points (CCPs), including reducing animal contact in the household, improving knowledge and practices around cooking processes and hygiene practices specific to the child such as handwashing and the use of cutlery. [ABSTRACT FROM AUTHOR]

Introduction: Unhealthy alcohol use significantly contributes to viral non‐suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub‐Saharan Africa (SSA). Methods: As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills‐based alcohol intervention among PWH with self‐reported unhealthy alcohol use (Alcohol Use Disorders Identification Test–Consumption [AUDIT‐C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non‐suppression, defined as either recent HIV viral non‐suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3‐month in‐person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT‐C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. Results: Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol‐serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93–1.1). Among PWH with baseline viral non‐suppression, 24‐week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93–1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79–0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56–0.88) than men (RR 0.93, 95% CI: 0.85–1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53–0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92–1.02). Conclusions: In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non‐suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV‐associated co‐morbidities. [ABSTRACT FROM AUTHOR]

Despite the significant role that dissolved organic phosphorus (DOP) plays in ecosystem productivity, efforts to characterize inputs of phosphorus (P) into lakes have largely ignored P fractions complexed to dissolved organic matter (DOM). To address this gap, we characterized DOP and DOM along a transect of a Lake Erie tributary (Kettle Creek) from the headwaters to the rivermouth and into the nearshore and offshore central basin. DOM and DOP characteristics impart a chemical fingerprint that is useful for determining source and production in aquatic ecosystems. We analyzed DOM composition and concentration (DOC; organic carbon) in addition to DOP as phosphomonoesters (MP; predominantly terrestrial in origin) and phosphodiesters (DP; microbially‐produced), along with other water quality parameters. DOM and DOC within the river were relatively invariant. While there were no consistent trends in riverine MP and DP, an impoundment on the river appeared to act as a sink for some soluble P forms and a potential source of DP. At the rivermouth, we observed a rapid decrease in DOC, DOP, and total P and a shift to more autochthonous‐like DOM, though the decrease in DP was weaker. Relative to in‐flowing river water, P pools in nearshore and offshore Lake Erie were enriched in DOP, especially DP. DOP accounted for up to 42% of total P in Kettle Creek and up to 92% in Lake Erie's central basin. Our work shows the importance of considering DOP in P management efforts as its dynamics differ from those of other, more commonly measured P forms. Plain Language Summary: Phosphorus and carbon are two essential nutrients that control many ecological processes in aquatic ecosystems such as algal and microbial growth. In rivers, organic phosphorus and organic carbon (DOC) can transfer from the land to the water or can be produced or transformed internally by microbes. These organic nutrients are then transported to lakes or oceans where they can be further transformed. The relationship between the dissolved fractions of these two nutrients and whether they are primarily derived from land or produced internally is not well known. Here we document the changes in DOC and organic phosphorus as they travel from a river's headwater to Lake Erie. We show that organic phosphorus and DOC are transformed into more microbial forms as the water moves from headwaters to the middle of Lake Erie. This could have implications for the management of phosphorus and the development of algal blooms. Key Points: Our findings highlight the importance of considering organic phosphorus (DOP) together with organic carbon (DOC) for phosphorus managementWe found rapid changes in DOP and DOC from headwaters to lakeFreshwater rivermouths are biogeochemical hotspots for processing DOP and DOC [ABSTRACT FROM AUTHOR]

Background: Topical azelaic acid (AA) is indicated for acne and rosacea, but there is some evidence for its use for other dermatological conditions. Aims: To assess the effectiveness and safety of topical AA for acne vulgaris, rosacea, hyperpigmentation/melasma, and skin aging. Methods: RCTs of at least 6 weeks' treatment duration were eligible for inclusion. Databases including MEDLINE, Embase, CINAHL, and ClinicalTrials.gov were searched up to December 2022. Two reviewers were involved in all stages of the systematic review process. Results: Forty‐three RCTs met the inclusion criteria. Meta‐analyses within 20 rosacea studies demonstrated that erythema severity, inflammatory lesion counts, overall improvement, and treatment success (achieving skin clarity) were significantly improved with AA compared with vehicle after 12 weeks. AA was more effective than metronidazole 0.75% for improved erythema severity, overall improvement, and inflammatory lesion counts. Sixteen acne studies suggest that AA is more effective than vehicle for improving global assessments and reducing acne severity. AA 20% also significantly reduced more lesions than erythromycin gel. Within seven melasma studies, AA 20% was significantly better than vehicle for both severity and global improvement. AA 20% demonstrated significantly better results compared with hydroquinone 2% for global improvement. Very few significant differences between AA and comparators were observed for commonly reported adverse events. No eligible RCTs were found that evaluated skin aging. Conclusions: AA is more effective than vehicle for rosacea, acne and melasma. Comparisons between AA and other treatments were often equivalent. Where there is equivalence, AA may be a good option for some clinical situations. RCT evidence is needed to evaluate the effectiveness of AA on skin aging. [ABSTRACT FROM AUTHOR]

Background: The use of biomarkers in behavioral HIV research can help to address limitations of self‐reported data. The COVID‐19 pandemic forced many researchers to transition from standard in‐person data collection to remote data collection. We present data on the feasibility of remote self‐collection of dried blood spots (DBS), hair, and nails for the objective assessment of alcohol use, antiretroviral therapy adherence, and stress in a sample of people with HIV (PWH) who are hazardous drinkers. Methods: Standardized operating procedures for remote self‐collection of DBS, hair, and nails were developed for an ongoing pilot study of a transdiagnostic alcohol intervention for PWH. Prior to each study appointment, participants were mailed a kit containing materials for self‐collection, instructions, a video link demonstrating the collection process, and a prepaid envelope for returning samples. Results: A total of 133 remote study visits were completed. For DBS and nail collection at baseline, 87.5% and 83.3% of samples, respectively, were received by the research laboratory, of which 100% of samples were processed. Although hair samples were intended to be analyzed, most of the samples (77.7%) were insufficient or the scalp end of the hair was not marked. We, therefore, decided that hair collection was not feasible in the framework of this study. Conclusion: An increase in remote self‐collection of biospecimens may significantly advance the field of HIV‐related research, permitting the collection of specimens without resource‐intensive laboratory personnel and facilities. Further research is needed on the factors that impeded participants' ability to complete remote biospecimen collection. [ABSTRACT FROM AUTHOR]

Continuous monitoring of glucose allows diabetic patients to better maintain blood glucose level by altering insulin dosage or diet according to prevailing glucose values and thus to prevent potential hyperglycemia and hypoglycemia. However, current continuous glucose monitoring (CGM) relies mostly on enzyme electrodes or micro-dialysis probes, which suffer from insufficient stability, susceptibility to corrosion of electrodes, weak or inconsistent correlation, and inevitable interference. A fluorescence-based glucose sensor in the skin will likely be more stable, have improved sensitivity, and can resolve the issues of electrochemical interference from the tissue. This study develops a fluorescent nanodiamond boronic hydrogel system in porous microneedles for CGM. Fluorescent nanodiamond is one of the most photostable fluorophores with superior biocompatibility. When surface functionalized, the fluorescent nanodiamond can integrate with boronic polymer and form a hydrogel, which can produce fluorescent signals in response to environmental glucose concentration. In this proof-of-concept study, the strategy for building a miniatured device with fluorescent nanodiamond hydrogel is developed. The device demonstrates remarkable long-term photo and signal stability in vivo with both small and large animal models. This study presents a new strategy of fluorescence based CGM toward treatment and control of diabetes. [ABSTRACT FROM AUTHOR]

We propose the hypothesis that small high‐density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Understanding factors driving resource selection and habitat use of different species is an important component of management and conservation. Feral horses (Equus caballus) are free ranging across various vegetation types in the western United States, yet few studies have quantified their resource selection and seasonal use. We conducted a study to determine effects of vegetation community, distance to water, and topographic variables on seasonal resource selection in 2 feral horse populations in Great Basin sagebrush (Artemisia spp.) ecosystems of west‐central Utah, USA: Conger Herd Management Area (HMA) and Frisco HMA. We deployed global positioning system (GPS) radio‐collars on 38 female horses and GPS‐transmitters braided and glued into the tail hair of 14 males, collecting locations every 2 hours for 1–4 years between 2016 and 2020. We calculated home range size and core use area of social groups (harems) and bachelor males using auto‐correlated kernel density estimators for each biologically defined season (breeding, fall, and winter) per study year. We examined seasonal home range size and overlap of harem groups and bachelor males and compared movement speed of bachelors and harems among seasons. We determined seasonal resource selection in a use‐availability framework using resource selection functions. We hypothesized that horses would select for areas of high herbaceous vegetation, that water would be a key variable in resource selection models like other equids, and home range size in winter would be largest because horses can eat snow for hydration and could therefore roam farther from surface water. Mean annual home range size was 103.12 ± 37.38 km2 (SD) for Conger harems and 117.47 ± 32.75 km2 for Frisco harems. At Conger there was no difference in home range size between harem groups and bachelor males, but home range size was smaller in winter than other seasons, whereas winter home range size at Frisco was larger than other seasons. Bachelor males moved at higher speeds than harems during all seasons, and harem groups from both populations had lower movement speeds in winter. Harem groups had distinct winter ranges with little overlap on breeding season ranges. In both populations, all horses selected for herbaceous vegetation types and avoided forest relative to shrubland throughout the year. Harems at Frisco were consistently located closer to water sources, whereas selection for water sources by Conger harems varied seasonally, with winter having the lowest selection. Harem groups at Conger had an average of 10.6% of their home ranges outside the HMA boundary and Frisco harems had up to 66.8% outside, likely because of the horseshoe shape of Frisco HMA in which shrub meadows (foraging areas) comprise the horseshoe center, which is outside the HMA. Our results highlight the importance of water sources, which were a key predictor of horse movement patterns in our study. We emphasize the utility of telemetry devices to understand resource selection of feral horses at a fine scale, enabling management to be more targeted and facilitate planning. [ABSTRACT FROM AUTHOR]

The APOE gene encoding the Apolipoprotein E protein is the single most significant genetic risk factor for late‐onset Alzheimer's disease. The APOE4 genotype confers a significantly increased risk relative to the other two common genotypes APOE3 and APOE2. Intriguingly, APOE4 has been associated with neuropathological and cognitive deficits in the absence of Alzheimer's disease‐related amyloid or tau pathology. Here, we review the extensive literature surrounding the impact of APOE genotype on central nervous system dysfunction, focussing on preclinical model systems and comparison of APOE3 and APOE4, given the low global prevalence of APOE2. A multi‐hit hypothesis is proposed to explain how APOE4 shifts cerebral physiology towards pathophysiology through interconnected hits. These hits include the following: neurodegeneration, neurovascular dysfunction, neuroinflammation, oxidative stress, endosomal trafficking impairments, lipid and cellular metabolism disruption, impaired calcium homeostasis and altered transcriptional regulation. The hits, individually and in combination, leave the APOE4 brain in a vulnerable state where further cumulative insults will exacerbate degeneration and lead to cognitive deficits in the absence of Alzheimer's disease pathology and also a state in which such pathology may more easily take hold. We conclude that current evidence supports an APOE4 multi‐hit hypothesis, which contributes to an APOE4 pathophysiological state. We highlight key areas where further study is required to elucidate the complex interplay between these individual mechanisms and downstream consequences, helping to frame the current landscape of existing APOE‐centric literature. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic presented numerous challenges to acute malnutrition screening and treatment. To enable continued case identification and service delivery while minimising transmission risks, many organisations and governments implemented adaptations to community‐based management of acute malnutrition (CMAM) programmes for children under 5. These included: Family mid‐upper arm circumference (MUAC); modified admission and discharge criteria; modified dosage of therapeutic foods; and reduced frequency of follow‐up visits. This paper presents qualitative findings from a larger mixed methods study to document practitioners' operational experiences and lessons learned from these adaptations. Findings reflect insights from 37 interviews representing 15 organisations in 17 countries, conducted between July 2020 and January 2021. Overall, interviewees indicated that adaptations were mostly well‐accepted by staff, caregivers and communities. Family MUAC filled screening gaps linked to COVID‐19 disruptions; however, challenges included long‐term accuracy of caregiver measurements; implementing an intervention that could increase demand for inconsistent services; and limited guidance to monitor programme quality and impact. Modified admission and discharge criteria and modified dosage streamlined logistics and implementation with positive impacts on staff workload and caregiver understanding of the programme. Reduced frequency of visits enabled social distancing by minimising crowding at facilities and lessened caregivers' need to travel. Concerns remained about how adaptations impacted children's identification for and progress through treatment and programme outcomes. Most respondents anticipated reverting to standard protocols once transmission risks were mitigated. Further evidence, including multi‐year programmatic data analysis and rigorous research, is needed in diverse contexts to understand adaptations' impacts, including how to ensure equity and mitigate unintended consequences. Key messages: COVID‐19 CMAM programme adaptations enabled service continuity despite pandemic‐related challenges. Further evidence is needed on long‐term impacts.Family MUAC was well‐accepted and addressed screening gaps from COVID‐19 disruptions. Challenges included sustaining caregiver measurement accuracy; handling inaccurate self‐referrals to encourage health‐seeking behaviours; and limited programme design and monitoring guidance and tools.Modified admission criteria and therapeutic food dosage reduced contact between staff and children and streamlined logistics and implementation. Concerns remained about effects on programme admissions and outcomes.Reduced frequency of follow‐up visits successfully reduced facility crowding and need for caregiver travel. However, infrequent monitoring of childrenmay miss deterioration. [ABSTRACT FROM AUTHOR]

The excavation by T. C. M Brewster and J. S. Dent between 1964 and 1989 of the multiperiod site at Wetwang Slack, East Yorkshire, has gained international importance for its square barrow cemetery and multiple Arras‐style Iron Age cart/chariot burials. A lesser known fact is that the excavations also produced the largest Iron Age faunal assemblage identified outside of southern Britain, in addition to several late Iron Age/early Romano‐British articulated animal bone groups (ABGs). The presence of pathological human and articulated faunal remains provides the unique opportunity to review the macroscopic evidence for zoonotic diseases, specifically bovine tuberculosis (bTB) in an Iron Age community where close working relationships with animals, the use of animal by‐products, and the consumption of infected dairy products all form potential avenues of infection. This paper presents the palaeopathological evidence for possible infectious disease in the ABGs at Wetwang Slack with a focus on bTB. Several cases of suspected tuberculosis are described in the human remains, with one example of gastrointestinal infection that could potentially indicate a case of bTB. Ancient DNA (aDNA) samples were taken from five ABGs testing for both Mycobacterium tuberculosis complex and Brucella pathogen DNA. The results were negative, but DNA degradation was highlighted as a contributing factor. This paper highlights the importance of considering the evidence for zoonotic diseases at sites where human and faunal assemblages are recovered and especially where articulated animal skeletons are present. The paper also emphasizes that future aDNA studies of diseased faunal remains should focus on smaller amplicons or whole genome sequencing to amplify pathogen DNA. [ABSTRACT FROM AUTHOR]

Aims: Among people with diabetes using insulin, severe hypoglycaemia (SH) can be a life‐threatening complication, if untreated. The personal experiences during an SH event from the perspectives of people with diabetes and their caregivers are not well‐characterized. This study assessed the perceptions of the event and the decision making processes of people with diabetes (T1D n = 36; T2D n = 24) and their caregivers during SH events. Methods: In‐depth one‐on‐one telephone interviews were conducted with dyads of people with diabetes and caregivers in the United States (n = 120). An initial synopsis and inductive codebook schema were used to analyse the data with two independent coders (kappa = 0.87–0.89). Themes were developed from the codes, and codes were re‐mapped to the themes. Results: Four themes were formed: (1) Caregivers scramble to do the right thing and support people with diabetes in treating SH; (2) Decision making capacity is impaired during an SH event, often a panicked time; (3) People learn to manage SH events through their own experiences and frequently make lifestyle changes to prevent and treat future events; and (4) Discussion with healthcare providers about SH, and particularly SH treatment, is limited. Conclusions: SH events are stressful and often evoke emotional reactions that can impair decision making. Thus, advance treatment planning of SH events needs to occur. Much of the knowledge about SH treatment derives from prior experience rather than healthcare provider guidance, suggesting a need for healthcare providers to initiate proactive discussions about SH treatment. [ABSTRACT FROM AUTHOR]

The forage maturation hypothesis (FMH) states that energy intake for ungulates is maximised when forage biomass is at intermediate levels. Nevertheless, metabolic allometry and different digestive systems suggest that resource selection should vary across ungulate species. By combining GPS relocations with remotely sensed data on forage characteristics and surface water, we quantified the effect of body size and digestive system in determining movements of 30 populations of hindgut fermenters (equids) and ruminants across biomes. Selection for intermediate forage biomass was negatively related to body size, regardless of digestive system. Selection for proximity to surface water was stronger for equids relative to ruminants, regardless of body size. To be more generalisable, we suggest that the FMH explicitly incorporate contingencies in body size and digestive system, with small‐bodied ruminants selecting more strongly for potential energy intake, and hindgut fermenters selecting more strongly for surface water. [ABSTRACT FROM AUTHOR]

Accurate population estimates provide the foundation for managing feral horses (Equus caballus ferus) across the western United States. Certain feral horse populations are protected by the Wild and Free‐Roaming Horses and Burros Act of 1971 and managed by the Bureau of Land Management (BLM) or the United States Forest Service on designated herd management areas (HMAs) or wild horse territories, respectively. Horses are managed to achieve an appropriate management level (AML), which represents the number of horses determined by BLM to contribute to a thriving natural ecological balance and avoid deterioration of the range. To achieve AML for each HMA, BLM resource managers need accurate and precise population estimates. We tested the use of non‐invasive fecal samples in a genetic capture‐recapture framework to estimate population size in a closed horse population at the Little Book Cliffs HMA, Colorado, USA, with a known size of 153 individuals. We collected 1,957 samples over 3 independent sampling periods in 2014 and amplified them at 8 microsatellite loci. We applied mark‐recapture models to determine population size using 954 samples that amplified at all 8 loci. We subsampled and reanalyzed our dataset to simulate different data collection protocols and evaluated effects on accuracy and precision of estimates using N‐mixture modeling, full likelihood closed‐capture modeling, and capwire single‐occasion modeling that used data from all 3 sampling periods. Our model results were accurate and precise for analyses that used data from all 3 occasions; however, capwire single‐occasion modeling was not accurate when we analyzed each sampling period separately. For all subsampling analysis scenarios, reducing sample size decreased precision, whether by reducing number of field staff, field days, or geographic areas surveyed on each period. Reducing spatial coverage of the survey area did not result in accurate population estimates and only marginally lowered the number of samples that would need to be collected to maintain accuracy. Because laboratory analysis contributes the greatest expense for this method ($80 U.S./sample), reducing fecal sample size is advantageous. Our results demonstrate that non‐invasive sampling combined with good survey design and careful genetic and capture‐recapture analyses can provide an alternative method to estimate the number of feral horses in a closed population. This method may be especially appropriate in situations where aerial inventories are not practical or accurate because of low sighting conditions. But the higher costs associated with laboratory sample analyses may reduce the method's feasibility compared to helicopter surveys. © 2021 The Wildlife Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA. : We evaluated the use of non‐invasive fecal sampling in a genetic capture‐recapture framework to estimate population size of feral horses. We compared results to known herd size and compared different field sampling scenarios aimed at reducing costs of the method. Fecal sampling combined with good survey design and careful genetic and capture‐recapture analyses successfully provided an alternative method to estimate number of feral horses in a closed population but is currently more expensive than helicopter surveys. [ABSTRACT FROM AUTHOR]

Feral horses (Equus ferus caballus) in the western United States are managed by the Bureau of Land Management (BLM) and United States Forest Service in designated areas on public lands with a goal of maintaining populations in balance with multiple uses of the landscape. Small, isolated populations can be at risk of extirpation from stochastic events and deleterious genetic effects resulting from inbreeding and reduced heterozygosity. The genetic diversity of feral horse herds is periodically monitored using blood or hair samples collected during management gathers (i.e., occasions when the herd is rounded up). We conducted a study to examine genetic characteristics of the feral horse population at the BLM Little Book Cliffs Herd Management Area (HMA) in Colorado, USA, using non‐invasively collected fecal samples. Additionally, we explored whether genotypes could be used to document space use and potential sub‐population development. We used a random sampling scheme, walking transects in sampling areas covering most of the HMA to find and collect fecal samples of all ages, except those that were deteriorating. We collected >1,800 fecal samples from across the study area in May, August, and October 2014. We then identified unique individuals using a suite of microsatellite loci. Our estimates of genetic diversity from fecal samples were higher than those reported from blood and hair samples taken during recent horse gathers, likely because our sample size and spatial distribution was larger. Genotypes revealed that some individuals were found only in certain parts of the study area and at a higher proportion than random; thus, they could be considered residents in those sampling areas. Using discriminant function analyses, we detected 5 genetic groups in the sample population, but these did not correspond to individuals in specific parts of the study area. Our results support the use of fecal DNA to augment direct observations of horse presence and could be used to detect habitat use and areas of high density. Non‐invasive techniques such as fecal DNA sampling can help managers decide whether new individuals need to be translocated to a closed population to maintain genetic diversity without the human safety and animal welfare concerns associated with gathers and invasive techniques. © 2021 The Wildlife Society. We found higher estimates of genetic diversity from feral horse fecal samples collected non‐invasively than those reported from blood or hair samples collected during a gather; genotypes derived from fecal samples can be used to show feral horse space use. Fecal samples can therefore be used to examine genetic characteristics of a horse herd in the absence of a gather and can elucidate areas of high horse use. [ABSTRACT FROM AUTHOR]

Background: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self‐reported alcohol use, we conducted an individual participant data (IPD) meta‐analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self‐reporting unhealthy alcohol consumption. Methods: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1‐step IPD meta‐analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index—BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger‐prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self‐reported alcohol use using the AUDIT‐C score. Results: One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT‐C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables. Conclusions: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible. [ABSTRACT FROM AUTHOR]

Impaired inhibitory control accompanied by enhanced salience attributed to drug‐related cues, both associated with function of the dorsolateral prefrontal cortex (dlPFC), are hallmarks of drug addiction, contributing to worse symptomatology including craving. dlPFC modulation with transcranial direct current stimulation (tDCS) previously showed craving reduction in inpatients with cocaine use disorder (CUD). Our study aimed at assessing feasibility of a longer tDCS protocol in CUD (15 versus the common five/10 sessions) and replicability of previous results. In a randomized double‐blind sham‐controlled protocol, 17 inpatients with CUD were assigned to either a real‐tDCS (right anodal/left cathodal) or a sham‐tDCS condition for 15 sessions. Following the previous report, primary outcome measures were self‐reported craving, anxiety, depression, and quality of life. Secondary measures included sleepiness, readiness to change drug use, and affect. We also assessed cognitive function including impulsivity. An 88% retention rate demonstrated feasibility. Partially supporting the previous results, there was a trend for self‐reported craving to decrease in the real‐tDCS group more than the sham‐group, an effect that would reach significance with 15 subjects per group. Quality of life and impulsivity improved over time in treatment in both groups. Daytime sleepiness and readiness to change drug use showed significant Group × Time interactions whereby improvements were noted only in the real‐tDCS group. One‐month follow‐up suggested transient effects of tDCS on sleepiness and craving. These preliminary results suggest the need for including more subjects to show a unique effect of real‐tDCS on craving and examine the duration of this effect. After replication in larger sample sizes, increased vigilance and motivation to change drug use in the real‐tDCS group may suggest fortification of dlPFC‐supported executive functions. [ABSTRACT FROM AUTHOR]

This article explores the FTA (or Free the Army) show, a touring antiwar performance led by Hollywood actors Jane Fonda and Donald Sutherland in 1971. FTA sought to support antiwar GIs who, by the early 1970s, constituted a GI movement opposed to the Vietnam War. FTA visited military towns in the continental United States, performing for an estimated 15,000 GIs and reflecting antiwar GIs' increasingly intersectional analysis of war, militarism, racism, and sexism. In November, the troupe traveled to the Asia‐Pacific—the staging ground for the American war effort in Vietnam—to perform for an additional 64,000 US troops in Hawaii, the Philippines, Japan, and Okinawa. Pitched as a counter‐USO show, FTA, which took its critique of the war to the doorstep of the US military, not only served as a megaphone for the under‐reported GI movement, but also evolved celebrity activism, taking it to new heights of oppositional politics. [ABSTRACT FROM AUTHOR]

The largest and tallest mountain range in the contiguous United States, the Southern Rocky Mountains, has warmed considerably in the past several decades due to anthropogenic climate change. Herein we examine how 47 mammal elevational ranges (27 rodent and 4 shrew species) have changed from their historical distributions (1886–1979) to their contemporary distributions (post 2005) along 2,400‐m elevational gradients in the Front Range and San Juan Mountains of Colorado. Historical elevational ranges were based on more than 4,580 georeferenced museum specimen and publication records. Contemporary elevational ranges were based on 7,444 records from systematic sampling efforts and museum specimen records. We constructed Bayesian models to estimate the probability a species was present, but undetected, due to undersampling at each 50‐m elevational bin for each time period and mountain range. These models leveraged individual‐level detection probabilities, the number and patchiness of detections across 50‐m bands of elevation, and a decaying likelihood of presence from last known detections. We compared 95% likelihood elevational ranges between historical and contemporary time periods to detect directional change. Responses were variable as 26 mammal ranges changed upward, 6 did not change, 11 changed downward, and 4 were extirpated locally. The average range shift was 131 m upward, while exclusively montane species shifted upward more often (75%) and displayed larger average range shifts (346 m). The best predictors of upper limit and total directional change were species with higher maximum latitude in their geographic range, montane affiliation, and the study mountain was at the southern edge of their geographic range. Thus, mammals in the Southern Rocky Mountains serve as harbingers of more changes to come, particularly for montane, cold‐adapted species in the southern portion of their ranges. [ABSTRACT FROM AUTHOR]

A general assumption in the use of biotelemetry is that tags do not affect the animal's behavior. There is general agreement that internal implantation of transmitters is the preferred method for affixing a tag to a fish relative to external and intragastric transmitters because internal tags have minimal negative impacts on growth and can be used for long‐term research. Internal transmitter attachment methods have only recently been explored for the family Lepisosteidae due to the inability to breach ganoid scales with traditional surgical procedures developed for teleost fishes. In this study, we used a recently developed specialized surgical technique to conduct sham surgeries on Shortnose Gar Lepisosteus platostomus to document short‐ and long‐term recovery and wound healing rates. Shortnose Gar were successfully sedated for surgical purposes with AQUI‐S 20E at a concentration of 250 mg/L, although we discovered that it is necessary to prevent facultative air breathing to ensure sufficient induction. Despite a longer sedation time relative to other species, fish recovered quickly and showed no adverse effects. Surgical wounds closed within approximately 2 weeks, and monofilament sutures were retained long enough to promote healing. On average, fish lost 0.34% body weight per day over the first 7–19 d postsurgery but gained 0.26% body weight per day over the remainder of the 478‐d study. Our study is the first to test the effective dosage of AQUI‐S 20E in Shortnose Gar and to evaluate recovery from surgery using a specialized surgical technique in a controlled setting. Methods used in our study were designed to be directly applied in the field, will allow researchers to safely utilize internal implantation of transmitters in primitive fishes with ganoid scales, and will enable studies that expand our knowledge of the spatial ecology and habitat use in this ancient lineage of fish. [ABSTRACT FROM AUTHOR]

BACKGROUND: In Spartanburg County, SC, nearly 33.7% of children are overweight or obese. The purpose of this study was to investigate differences in eating behavior of youth by race/ethnicity and socioeconomic status. METHODS: Students (N = 997) in 4th to 5th grades completed the School Nutrition and Physical Activity Survey. School databases categorized students as either White or racial/ethnic minority and free/reduced or full paid lunch status. Dietary behaviors included 13 composite measures: unhealthy proteins, healthy proteins, dairy, refined grains, whole grains, vegetables, fruit, fried snacks, sugar‐sweetened beverages, sweets, and consumption of a breakfast, evening, and/or restaurant meal. Logistic regression, controlling for sex, was used to analyze differences in consumption for each nutrition variable. RESULTS: Minority youth were less likely to consume healthy proteins (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.55‐0.92) and more likely to eat at a restaurant (OR = 1.32, 95% CI = 1.02‐1.70) compared to white youth. Lower socioeconomic status youth were less likely to eat an evening meal compared to higher socioeconomic status youth (OR = 0.59, 95% CI = 0.39‐0.89). CONCLUSIONS: Differences in dietary behaviors may result from food accessibility and insecurity in minority and/or low‐income neighborhoods. Future research should explore policy strategies that can help ensure all youth maintain healthy eating habits and weight status. [ABSTRACT FROM AUTHOR]

Background: Self‐report is widely used to assess alcohol use in research and clinical practice, but may be subject to social desirability bias. We aimed to determine if social desirability impacts self‐reported alcohol use. Methods: Among 751 human immunodeficiency virus (HIV)‐infected patients from a clinic in southwestern Uganda, we measured social desirability using the Marlowe–Crowne Social Desirability Scale (SDS) Short Form C, self‐reported alcohol use (prior 3 months) Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C), and phosphatidylethanol (PEth), a biomarker of prior 3 weeks' drinking. We conducted multiple regression analyses to assess the relationship between SDS score (low, medium, and high levels) and (i) any self‐reported recent alcohol use, among those who were PEth‐positive (≥8 ng/ml), and (ii) continuous AUDIT‐C score, among those reporting any recent alcohol use. We controlled for PEth level, age, gender, education, economic assets, marital status, religion, spirituality/religiosity, social support, and study cohort. Results: Of 751 participants, 59% were women; the median age was 31 years (interquartile range [IQR]: 26 to 39). Median SDS score was 9 (IQR: 4 to 10). Two‐thirds (62%) self‐reported any recent alcohol use; median AUDIT‐C was 1 (IQR: 0 to 4). Among those who were PEth‐positive (57%), 13% reported no recent alcohol use. Those with the highest SDS tertile had decreased odds of reporting any recent alcohol use compared to the lowest tertile, but the association did not reach statistical significance in multivariable analyses (adjusted odds ratio 0.55 [95% confidence interval (CI): 0.25, 1.23]). Among participants self‐reporting recent alcohol use, SDS level was negatively associated with AUDIT‐C scores (adjusted β: −0.70 [95% CI: −1.19, −0.21] for medium vs. low SDS and −1.42 [95% CI: −2.05, −0.78] for high vs. low SDS). Conclusions: While use of objective measures (e.g., alcohol biomarkers) is desirable for measuring alcohol use, SDS scores may be used to adjust self‐reported drinking levels by participants' level of social desirability in HIV research studies. [ABSTRACT FROM AUTHOR]

Aim: Species richness is often strongly correlated with climate. The most commonly invoked mechanism for this climate‐richness relationship is the more‐individuals‐hypothesis (MIH), which predicts a cascading positive influence of climate on plant productivity, food resources, total number of individuals, and species richness. We test for a climate‐richness relationship and an underlying MIH mechanism, as well as testing competing hypotheses including positive effects of habitat diversity and heterogeneity, and the species‐area effect. Location: Colorado Rocky Mountains, USA: two elevational gradients in the Front Range and San Juan Mountains. Methods: We conducted standardized small mammal surveys at 32 sites to assess diversity and population sizes. We estimated vegetative and arthropod food resources as well as various aspects of habitat structure by sampling 20 vegetation plots and 40 pitfall traps per site. Temperature, precipitation and net primary productivity (NPP) were assessed along each gradient. Regressions and structural equation modelling were used to test competing diversity hypotheses and mechanistic links predicted by the MIH. Results: We detected 3,922 individuals of 37 small mammal species. Mammal species richness peaked at intermediate elevations, as did productivity, whereas temperature decreased and precipitation increased with elevation. We detected strong support for a productivity‐richness relationship, but no support for the MIH mechanism. Food and mammal population sizes were unrelated to NPP or mammal species richness. Furthermore, mammal richness was unrelated to habitat diversity, habitat heterogeneity, or elevational area. Main conclusions: Sites with high productivity contain high mammal species richness, but a mechanism other than a contemporary MIH underlies the productivity–diversity relationship. Possibly a mechanism based on evolutionary climatic affiliations. Protection of productive localities and mid‐elevations are the most critical for preserving small mammal richness, but may be decoupled from trends in population sizes, food resources, or habitat structure. [ABSTRACT FROM AUTHOR]

Abstract: Recreational angling for gars (family Lepisosteidae) has become more popular in recent years; however, the fundamental understanding of their population dynamics needed for effective management and conservation is lacking. Age data are essential for describing population dynamic rate functions, but few studies have addressed the selection of ideal calcified structures for estimating age in gars. We collected Spotted Gars Lepisosteus oculatus, Shortnose Gars L. platostomus, and Longnose Gars L. osseus from 12 Illinois water bodies to assess the relative bias and precision of age estimates derived from branchiostegal rays, pectoral fin rays, cleithra, and sagittal otoliths. Age assignments differed among these calcified structures for all three species. Branchiostegal rays underestimated the age of young fish and overestimated the age of old fish relative to all other structures. Pectoral fin rays consistently underestimated age relative to other structures and produced the lowest mean and maximum age estimates. Although there was low relative bias between readers for all structures, age assignments showed greater variability between readers for old age‐classes when age estimates were derived from cleithra and otoliths. Between‐reader precision was highest using pectoral fin rays, whereas cleithra and otoliths generated lower coefficients of variation and percent agreement values. These findings reveal a need to improve or modify structure processing methods to increase readability when cleithra and otoliths are used for age estimation. Given these results, future validation studies should target branchiostegal rays and pectoral fin rays to determine the most accurate calcified structure for aging gars. [ABSTRACT FROM AUTHOR]

Abstract: Fecal DNA collected noninvasively can provide valuable information about genetic and ecological characteristics. This approach has rarely been used for equids, despite the need for conservation of endangered species and management of abundant feral populations. We examined factors affecting the efficacy of using equid fecal samples for conservation genetics. First, we evaluated two fecal collection methods (paper bag vs. ethanol). Then, we investigated how time since deposition and month of collection impacted microsatellite amplification success and genotyping errors. Between May and November 2014, we collected feral horse fecal samples of known age each month in a feral horse Herd Management Area in western Colorado and documented deterioration in the field with photographs. Samples collected and dried in paper bags had significantly higher amplification rates than those collected and stored in ethanol. There was little difference in the number of loci that amplified per sample between fresh fecal piles and those that had been exposed to the environment for up to 2 months (in samples collected in paper bags). After 2 months of exposure, amplification success declined. When comparing fresh (0–2 months) and old (3–6 months) fecal piles, samples from fresh piles had more matching genotypes across samples, better amplification success and less allelic dropout. Samples defecated during the summer and collected within 2 months of deposition had highest number of genotypes matching among samples, and lowest rates of amplification failure and allelic dropout. Due to the digestive system and amount of fecal material produced by equids, as well as their occurrence in arid ecosystems, we suggest that they are particularly good candidates for noninvasive sampling using fecal DNA. [ABSTRACT FROM AUTHOR]

Human activities can cause large alterations in biogeochemical cycles of key nutrients such as carbon (C), nitrogen (N), and phosphorus (P). However, relatively little is known about how these changes alter the proportional fluxes of these elements across ecosystem boundaries from rivers to lakes. Here, we examined environmental factors influencing spatial and temporal variation in particulate C : N : P ratios across the Lake Erie watershed from its tributaries to its outflow. Throughout the study, particulate nutrient ratios ranged widely (C : N 2.0-25.8, C : P 32-530, N : P 3.7-122.9), but mean values were generally lower than previous estimates from different aquatic environments. Particulate C : N ratios varied the least across all environments, but C : P and N : P ratios increased between tributaries and coastal areas and throughout the growing season in coastal environments. These ratios also differed temporally in offshore waters as particulate C : P and N : P were higher in the spring and summer and lower in the fall and winter. Particulate C : P ratios also increased between the western/central and eastern basins indicating differential nutrient processing across the lake. These stoichiometric changes were associated with unique environmental factors among ecosystems as tributary stoichiometry was related to terrestrial land use and land cover, coastal ratios were a product of mixing between riverine and offshore waters, and offshore patterns were influenced by differences in temperature and particulate nutrient loading among basins. Overall, by studying changes in particulate C : N : P ratios across the Lake Erie watershed, our study demonstrates the power of using mass balance principles to study nutrient transformations along the aquatic continuum. [ABSTRACT FROM AUTHOR]

Whole-genome-shotgun ( WGS) sequencing of total genomic DNA was used to recover ~1 Mbp of novel mitochondrial (mt DNA) sequence from Pinus sylvestris (L.) and three members of the closely related Pinus mugo species complex. DNA was extracted from megagametophyte tissue from six mother trees from locations across Europe, and 100-bp paired-end sequencing was performed on the Illumina HiSeq platform. Candidate mt DNA sequences were identified by their size and coverage characteristics, and by comparison with published plant mitochondrial genomes. Novel variants were identified, and primers targeting these loci were trialled on a set of 28 individuals from across Europe. In total, 31 SNP loci were successfully resequenced, characterizing 15 unique haplotypes. This approach offers a cost-effective means of developing marker resources for mitochondrial genomes in other plant species where reference sequences are unavailable. [ABSTRACT FROM AUTHOR]

The intestinal epithelium is the fastest regenerative tissue in the body, fueled by fast-cycling stem cells. The number and identity of these dividing and migrating stem cells are maintained by a mosaic pattern at the base of the crypt. How the underlying regulatory scheme manages this dynamic stem cell niche is not entirely clear. We stimulated intestinal organoids with Notch ligands and inhibitors and discovered that intestinal stem cells employ a positive feedback mechanism via direct Notch binding to the second intron of the Notch1 gene. Inactivation of the positive feedback by CRISPR/Cas9 mutation of the binding sequence alters the mosaic stem cell niche pattern and hinders regeneration in organoids. Dynamical system analysis and agent-based multiscale stochastic modeling suggest that the positive feedback enhances the robustness of Notch-mediated niche patterning. This study highlights the importance of feedback mechanisms in spatiotemporal control of the stem cell niche. [ABSTRACT FROM AUTHOR]

The presence of the e4 allele of the apolipoprotein E ( APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1-weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using self-report alone. Design A prospective 1-year observational cohort study with quarterly visits. Setting Large rural HIV clinic in Mbarara, Uganda. Participants A total of 208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption. Measurements Unhealthy drinking was PEth+ (≥ 50 ng/ml) or Alcohol Use Disorders Identification Test-Consumption+ (AUDIT-C+, over 3 months, women ≥ 3; men ≥ 4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, antiretroviral therapy (ART), gender and self-reported prior unhealthy alcohol use. Findings The majority of participants (64%) were unhealthy drinkers (PEth+ or AUDIT-C+) at baseline. There was no significant trend in unhealthy drinking overall [per-month AOR: 1.01; 95% confidence interval (CI) = 0.94-1.07], while the per-month AORs were 0.91 (95% CI = 0.83-1.00) and 1.11 (95% CI = 1.01-1.22) when participants were not yet on ART and on ART, respectively (interaction P-value < 0.01). In contrast, 44% were AUDIT-C+; the per-month AORs for being AUDIT-C+ were 0.89 (95% CI = 0.85-0.95) overall, and 0.84 (95% CI = 0.78-0.91) and 0.97 (95% CI = 0.89-1.05) when participants were not on and were on ART, respectively. Conclusions Unhealthy alcohol use among Ugandan adults entering HIV care declines prior to the start of anti-retroviral therapy but rebounds with time. Augmenting self-reported alcohol use with biomarkers increases the ability of current alcohol use measurements to detect unhealthy alcohol use. [ABSTRACT FROM AUTHOR]

GalNAc-type O-glycosylation is found on most proteins trafficking through the secretory pathway in metazoan cells. The O-glycoproteome is regulated by up to 20 polypeptide GalNAc-Ts and the contributions and biological functions of individual GalNAc-Ts are poorly understood. Here, we used a zinc-finger nuclease (ZFN)- directed knockout strategy to probe the contributions of the major GalNAc-Ts (GalNAc-T1 and GalNAc-T2) in liver cells and explore how the GalNAc-T repertoire quantitatively affects the O-glycoproteome. We demonstrate that the majority of the O-glycoproteome is covered by redundancy, whereas distinct subsets of substrates are modified by non-redundant functions of GalNAc-T1 and GalNAc-T2. The non-redundant O-glycoproteome subsets and specific transcriptional responses for each isoform are related to different cellular processes; for the GalNAc-T2 isoform, these support a role in lipid metabolism. The results demonstrate that GalNAc-Ts have different non-redundant glycosylation functions, which may affect distinct cellular processes. The data serves as a comprehensive resource for unique GalNAc-T substrates. Our study provides a new view of the differential regulation of the O-glycoproteome, suggesting that the plurality of GalNAc-Ts arose to regulate distinct protein functions and cellular processes. [ABSTRACT FROM AUTHOR]

Model predictions of extinction risks from anthropogenic climate change are dire, but still overly simplistic. To reliably predict at-risk species we need to know which species are currently responding, which are not, and what traits are mediating the responses. For mammals, we have yet to identify overarching physiological, behavioral, or biogeographic traits determining species' responses to climate change, but they must exist. To date, 73 mammal species in North America and eight additional species worldwide have been assessed for responses to climate change, including local extirpations, range contractions and shifts, decreased abundance, phenological shifts, morphological or genetic changes. Only 52% of those species have responded as expected, 7% responded opposite to expectations, and the remaining 41% have not responded. Which mammals are and are not responding to climate change is mediated predominantly by body size and activity times (phylogenetic multivariate logistic regressions, P < 0.0001). Large mammals respond more, for example, an elk is 27 times more likely to respond to climate change than a shrew. Obligate diurnal and nocturnal mammals are more than twice as likely to respond as mammals with flexible activity times ( P < 0.0001). Among the other traits examined, species with higher latitudinal and elevational ranges were more likely to respond to climate change in some analyses, whereas hibernation, heterothermy, burrowing, nesting, and study location did not influence responses. These results indicate that some mammal species can behaviorally escape climate change whereas others cannot, analogous to paleontology's climate sheltering hypothesis. Including body size and activity flexibility traits into future extinction risk forecasts should substantially improve their predictive utility for conservation and management. [ABSTRACT FROM AUTHOR]

Context is critically important to the study of indigenous religions in North America. This paper argues that the significance of context to indigenous (native, Indian, tribal, or aboriginal) religions is unique and particular. In studying indigenous religions, attending to context engages geographical, political, and methodological issues, which emphasize the diversity of indigenous ideas and experience. The Mi'kmaq relationship to their homeland, Mi'kma'ki, demonstrates the importance of land as fundamental context for indigenous religions; the figure of Kateri Tekakwitha illuminates the inextricably political nature of indigenous religions. Finally, methods, theories, and practices (such as self-reflexivity) that have arisen in indigenous contexts are important analytical tools in the study of indigenous ways of knowing/practices. [ABSTRACT FROM AUTHOR]

Apolipoprotein E is a protein involved in cholesterol and lipid transport. The gene coding for this protein has three different alleles: e2, e3 and e4. The e4 allele is recognised as a significant risk factor for the development of Alzheimer's disease in later life. Paradoxically, behavioural and functional evidence has demonstrated that the e4 allele may confer a cognitive advantage to the carrier in youth. In this article, a range of sophisticated and novel structural imaging techniques were used to identify subtle differences in the brain tissue of groups of young e4 and homozygous e3 carriers that might support this paradox. Using voxel-based morphometry of high-resolution structural MR images, we identified a higher white matter volume ratio in e4 relative to homozygous e3 carriers. Furthermore, diffusion tensor imaging and tract-based spatial statistics studies identified increases in axial diffusivity and mode of anisotropy in carriers of the e4 allele. In addition, quantitative magnetisation transfer data were analysed using tract-based spatial statistics. Evidence of a trend towards an increased transverse relaxation time of the bound proton pool was detected in e4 carriers, indicative of altered white matter composition. These changes were found to correlate with indices of cognitive performance across the two groups, supporting the notion that such subtle differences in white matter integrity may confer neural advantages that contribute to cognitive outcomes and, potentially, to performance differences, such as observed here in a test of verbal fluency and reported previously by other researchers. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Previous research and popular conceptualizations of suicide have posited that many suicides are the result of impulsive, "on a whim" decisions. However, recent research demonstrates that most suicides are not attempted impulsively, and in fact involve a plan. Legally, suicide has historically been considered to be a superseding intervening cause of death that exonerates other parties from liability, but currently there are two general exceptions to this view. Specifically, another party may be found responsible for a suicide if that party either caused the suicide or failed in its duty to prevent the suicide from occurring. Both of these exceptions assume that the resulting suicide was foreseeable. Given that recent research has indicated that most suicides are planned, and thereby foreseeable to a certain extent under many circumstances, this article discusses issues of foreseeability as they pertain to litigation involving third party liability for the suicide of university students, prison inmates, and mental health patients. The authors contend that the surest way for universities, prison staff, and mental health practitioners to avoid being held liable for a suicide is to appropriately assess for suicidal intent. [ABSTRACT FROM AUTHOR]

The article cites key findings from the carbon and nitrogen isotopic analysis of bone collagen from the skeletal remains of young children under six years old and infants taken from the Wetwang Slack cemetery site in East Yorkshire, England. The research investigates infant diet, specifically weaning and breastfeeding practices, in Great Britain during the Iron Age. Also cited are the issues' implications for physical anthropology.