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Advanced endometrial cancer is associated with poor outcomes and few treatment options exist. Recently, the US Federal Drug Administration approved pembrolizumab for the treatment of endometrial cancers that are deficient in mismatch repair and have high microsatellite instability (MSI). Lynch syndrome is an autosomal dominant disease that causes MSI-high endometrial cancer. We report a case of a 46-year-old woman with Lynch syndrome and advanced endometrial cancer who experienced progressive disease after treatment with chemotherapy with carboplatin and paclitaxel. She was then treated with single-agent pembrolizumab and had an exceptional response. She was noted to have a significant decrease in the size of a large uterine mass extending into the vagina and vulva, as well as decrease in the size of lymphadenopathy. Data are limited at this time for patients with Lynch syndrome treated with single-agent pembrolizumab. Our case report seeks to add to the body of literature that suggests that this patient population may particularly benefit from this novel therapy.

Abstract In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was −5.8% (−651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.

Abstract Background Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks. Methodology We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak. Results Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15–60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0–300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred. Conclusions Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.

Thomas et al. test 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. Across 20 household outbreaks, antibody responses are heterogeneous, but a reliable indicator of recent infection.

Background: We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. Methods: The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. Results: For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. Conclusions: CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

This Special Issue of Animals was launched to promote the discussion of how animal welfare can be best addressed in zoos and aquariums while accommodating conservation needs, as well as how further improvements can be made in a similar vein to how medical and scientific research has advanced human health and welfare [...]

The presence of mutagenic and carcinogenic N-nitrosamine impurities in medicinal products poses a safety risk. While incorporating antioxidants in formulations is a potential mitigation strategy, concerns arise regarding their interference with drug absorption by inhibiting intestinal drug transporters. Our study screened thirty antioxidants for inhibitory effects on key intestinal transporters—OATP2B1, P-gp, and BCRP in HEK-293 cells (OATP2B1) or membrane vesicles (P-gp, BCRP) using 3H-estrone sulfate, 3H-N-methyl quinidine, and 3H-CCK8 as substrates, respectively. The screen identified that butylated hydroxyanisole (BHA) and carnosic acid inhibited all three transporters (OATP2B1, P-gp, and BCRP), while ascorbyl palmitate (AP) inhibited OATP2B1 by more than 50%. BHA had IC50 values of 71 ± 20 µM, 206 ± 14 µM, and 182 ± 49 µM for OATP2B1, BCRP, and P-gp, respectively. AP exhibited IC50 values of 23 ± 10 µM for OATP2B1. The potency of AP and BHA was tested with valsartan, an OATP2B1 substrate, and revealed IC50 values of 26 ± 17 µM and 19 ± 11 µM, respectively, in HEK-293-OATP2B1 cells. Comparing IC50 values of AP and BHA with estimated intestinal concentrations suggests an unlikely inhibition of intestinal transporters at clinical concentrations of drugs formulated with antioxidants.

We assessed the impact of respiratory syncytial virus (RSV) preventive characteristics on the intentions of pregnant people and healthcare providers (HCPs) to protect infants with a maternal vaccine or monoclonal antibodies (mAbs). Pregnant people and HCPs who treated pregnant people and/or infants were recruited via convenience sample from a general research panel to complete a cross-sectional, web-based survey, including a discrete choice experiment (DCE) wherein respondents chose between hypothetical RSV preventive profiles varying on five attributes (effectiveness, preventive type [maternal vaccine vs. mAb], injection recipient/timing, type of medical visit required to receive the injection, and duration of protection during RSV season) and a no-preventive option. A best–worst scaling (BWS) exercise was included to explore the impact of additional attributes on preventive preferences. Data were collected between October and November 2022. Attribute-level preference weights and relative importance (RI) were estimated. Overall, 992 pregnant people and 310 HCPs participated. A preventive (vs. none) was chosen 89.2% (pregnant people) and 96.0% (HCPs) of the time (DCE). Effectiveness was most important to preventive choice for pregnant people (RI = 48.0%) and HCPs (RI = 41.7%); all else equal, pregnant people (RI = 5.5%) and HCPs (RI = 7.2%) preferred the maternal vaccine over mAbs, although preventive type had limited influence on choice. Longer protection, protection starting at birth or the beginning of RSV season, and use for both pre-term and full-term babies were ranked highest in importance (BWS). Pregnant people and HCPs strongly preferred a preventive to protect infants against RSV (vs. none), underscoring the need to incorporate RSV preventives into routine care.

Fabry disease (FD) is an X-linked lysosomal storage disorder, characterised by the cellular accumulation of globotriaosylceramide due to impaired alpha-galactosidase A enzyme activity. FD may manifest with multisystem pathology, including reduced bone mineral density (BMD). Registry data suggest that the introduction of Fabry-specific therapies (enzyme replacement therapy or chaperone therapy) has led to significant improvements in overall patient outcomes; however, there are limited data on the impact on bone density. The aim of this study was to describe the effect of Fabry-specific therapies on longitudinal changes in bone mineral density (BMD) in FD. We performed a retrospective observational study analysing bone densitometry (DXA) in patients with genetically confirmed FD. Patients were grouped based on the use of Fabry-specific therapies. The between-group longitudinal change in BMD Z-score was analysed using linear mixed effects models. A total of 88 FD patients were analysed (50 untreated; 38 treated). The mean age at first DXA was 38.5 years in the untreated group (84% female) and 43.7 years in the treated group (34% female). There was no significant longitudinal between-group difference in the BMD Z-score at the lumbar spine. However, the Z-score per year at the total hip (β = −0.105, p < 0.001) and femoral neck (β = −0.081, p = 0.001) was significantly lower over time in the treated than the untreated group. This may reflect those receiving therapy having a more severe underlying disease. Nevertheless, this suggests that Fabry-specific therapies do not reverse all disease mechanisms and that the additional management of BMD may be required in this patient population.

Fetal and neonatal exposures to perinatal oxidative stress (OS) are key mediators of bronchopulmonary dysplasia (BPD). To characterize these exposures, adductomics is an exposure science approach that captures electrophilic addition products (adducts) in blood protein. Adducts are bound to the nucleophilic cysteine loci of human serum albumin (HSA), which has a prolonged half-life. We conducted targeted and untargeted adductomics to test the hypothesis that adducts of OS vary with BPD. We studied 205 preterm infants (≤28 weeks) and 51 full-term infants from an ongoing birth cohort. Infant plasma was collected at birth (cord blood), 1-week, 1-month, and 36-weeks postmenstrual age. HSA was isolated from plasma, trypsin digested, and analyzed using high-performance liquid chromatography–mass spectrometry to quantify previously annotated (known) and unknown adducts. We identified 105 adducts in cord and postnatal blood. A total of 51 known adducts (small thiols, direct oxidation products, and reactive aldehydes) were increased with BPD. Postnatally, serial concentrations of several known OS adducts correlated directly with supplemental oxygen exposure. The application of large-scale adductomics elucidated OS-mediated pathways of BPD. This is the first study to investigate the “neonatal–perinatal exposome” and to identify oxidative stress-related exposure biomarkers that may inform antioxidant strategies to protect the health of future generations of infants.

OBJECTIVES/GOALS: We designed the Biocascade Exhaled Breath Sampler (BEBS) to characterize viral aerosol shedding among individuals with influenza and other respiratory virus infections. We first aimed to test the BEBS on volunteer COVID-19 cases and report the aerodynamic size distribution of exhaled breath aerosol particles carrying SARS-CoV-2 RNA. METHODS/STUDY POPULATION: From June 15 through December 15, 2022, we recruited 27 PCR-confirmed COVID-19 cases from a college campus and the surrounding community to provide 30-minute breath samples into a well-validated Gesundheit-II (G-II) exhaled breath aerosol sampler. Among these individuals, 17 provided an additional exhaled breath sample into the newly designed BEBS. We quantified samples for viral RNA using reverse transcription digital polymerase chain reaction (RT-dPCR) and determined the viral RNA copies collected within two aerosol size fractions (≤5 µm and >5 µm in diameter) from the G-II, and four aerosol size fractions (8.2 µm) from the BEBS. RESULTS/ANTICIPATED RESULTS: Individuals with a SARS-CoV-2 Omicron BA.4 or BA.5 infection shed virus in aerosols at an average rate of 7.5x103 RNA copies per 30-minute G-II sample, with 78% of the total RNA in aerosols ≤5 µm in diameter. Among the BEBS samples, 10% of the total viral RNA was detected in aerosols 8.2 µm size fraction. Based on viral RNA loads, our results indicate that exhaled aerosols ≤3.2 µm contribute the majority of SARS-CoV-2 inhalation exposure. DISCUSSION/SIGNIFICANCE: Our data provide additional evidence that respirable aerosols contribute to the spread of SARS-CoV-2. Thus, our data suggest that mitigation measures designed to reduce infectious aerosol inhalation, such as ventilation and the use of air cleaners and respirators, are needed to control the spread.

Creative or novel behaviors in bottlenose dolphins (Tursiops truncatus) can be indicators of flexible thinking and problem solving. Over 50 years ago, two rough-tooth dolphins demonstrated creative novel behaviors acquired through reinforcement training in human care. Since this novel training, a variety of species have been trained to respond to this conceptual cue. The current study assessed the creativity of 12 bottlenose dolphins (5 females, 7 males) housed at the Roatan Institute for Marine Sciences (RIMS) in Roatan, Honduras. Individual differences were found across four constructs measured for creativity: fluency, flexibility, elaboration, and originality. Variability in performance occurred across test sessions. Animals with less experience with this task performed fewer “innovative” behaviors as compared to more experienced animals. Despite errors, dolphins continued to attempt the task during test sessions, suggesting the concept of “innovate” was intrinsically rewarding and cognitively engaging. This task may be utilized across species to promote the comparative study of innovative or creative behavior as well as to promote cognitive welfare.

This article offers a pedagogical approach to introducing undergraduate students to hagiology by comparing medieval sanctity to modern celebrity. The bodies of saints and celebrities are important loci for the transmission of sanctity or celebrity from a person to the public and for the continuity of identity. Examples include St. Faith, St. Cuthbert, Kim Kardashian, and Marilyn Monroe. Using a comparative method allows students who are non-religious to better apprehend the unfamiliar practices and beliefs around the cult of saints and relics.

The Tibetan Plateau (TP) is often referred to as the “Asian Water Tower”, as it plays a crucial role in supplying water for ∼1.9 billion people. Lakes in this arid mountain region have a wide salinity gradient and are sensitive to the complex interactions between climate and the water cycle, affecting aquatic ecosystems and species distributions. Here, we analyzed relationships between measured environmental variables and the spatial distribution of surface sediment diatom assemblages from 45 lakes located throughout the TP with the intention of developing a diatom-inference model for salinity. Diatom assemblage composition and diversity differed among lakes from the western (W), southern (S), northern (N), and southeastern (E) regions of the TP. The most common taxa observed in the lake set, Pantocsekiella ocellata, Nitzschia palea, and Staurosira venter, tended to have widespread distributions across the TP. In general, diatom diversity and richness tended to be highest in lakes with salinity concentrations between 0.1 and 10 g/L and were lowest in high salinity lakes (>20 g/L) of the N region. Canonical correspondence analysis (CCA) identified lake water salinity and maximum lake depth as explaining a statistically significant portion of diatom assemblage variation. Weighted-averaging (WA) was used to develop a diatom-based salinity inference model (R2jack = 0.71, RMSEPjack = 0.28) based on diatom optima from freshwater to meso-hyposaline lakes of the TP. Diatom-salinity reconstructions and changes in diatom community composition can potentially be used to track long-term patterns in climate and environmental conditions across the highly complex mountain landscape of the TP.

Abstract INTRODUCTION Diabetes and overweight/obesity are described as accelerating aging processes, yet many individuals with these conditions maintain high levels of cognitive and physical function and independence late into life. The Look AHEAD Aging study is designed to identify 20‐year trajectories of behaviors, risk factors, and medical history associated with resilience against geriatric syndromes and aging‐related cognitive and physical functional deficits among individuals with these conditions. METHODS Look AHEAD Aging extends follow‐up of the cohort of the former 10‐year Look AHEAD trial. The original cohort (N = 5145) was enrolled in 2001 to 2004 when participants were aged 45 to 76 years and randomly assigned to a multidomain intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) condition. The trial interventions ceased in 2012. Clinic‐based follow‐up continued through 2020. In 2021, the cohort was invited to enroll in Look AHEAD Aging, an additional 4‐year telephone‐based follow‐up (every 6 months) enhanced with Medicare linkage. Standardized protocols assess multimorbidity, physical and cognitive function, health care utilization, and health‐related quality of life. RESULTS Of the original N = 5145 Look AHEAD participants, N = 1552 active survivors agreed to participate in Look AHEAD Aging. At consent, the cohort's mean age was 76 (range 63 to 94) years and participants had been followed for a mean of 20 years. Of the original Look AHEAD enrollees, those who were younger, female, or with no history of cardiovascular disease were more likely to be represented in the Look AHEAD Aging cohort. Intervention groups were comparable with respect to age, diabetes duration, body mass index, insulin use, hypertension, cardiovascular disease, and cognitive function. ILI participants had significantly lower deficit accumulation index scores. DISCUSSION By continuing the long‐term follow‐up of an extensively characterized cohort of older individuals with type 2 diabetes, Look AHEAD Aging is well positioned to identify factors associated with resilience against aging‐related conditions.

Abstract Introduction The population of 16 million children exposed to HIV and uninfected (CHEU) under 15 years of age continues to expand rapidly, and the estimated prevalence of CHEU exceeds 20% in several countries in sub‐Saharan Africa with high HIV prevalence. Some evidence suggests that CHEU experience suboptimal neurodevelopmental outcomes compared to children born to women without HIV. In this commentary, we discuss the latest research on biologic and socio‐behavioural factors associated with neurodevelopmental outcomes among CHEU. Discussion Some but not all studies have noted that CHEU are at risk of poorer neurodevelopment across multiple cognitive domains, most notably in language and motor skills, in diverse settings, ages and using varied assessment tools. Foetal HIV exposure can adversely influence infant immune function, structural brain integrity and growth trajectories. Foetal exposure to antiretrovirals may also influence outcomes. Moreover, general, non‐CHEU‐specific risk factors for poor neurodevelopment, such as preterm birth, food insecurity, growth faltering and household violence, are amplified among CHEU; addressing these factors will require multi‐factorial solutions. There is a need for rigorous harmonised approaches to identify children at the highest risk of delay. In high‐burden HIV settings, existing maternal child health programmes serving the general population could adopt structured early child development programmes that educate healthcare workers on CHEU‐specific risk factors and train them to conduct rapid neurodevelopmental screening tests. Community‐based interventions targeting parent knowledge of optimal caregiving practices have shown to be successful in improving neurodevelopmental outcomes in children and should be adapted for CHEU. Conclusions CHEU in sub‐Saharan Africa have biologic and socio‐behavioural factors that may influence their neurodevelopment, brain maturation, immune system and overall health and wellbeing. Multidisciplinary research is needed to disentangle complex interactions between contributing factors. Common environmental and social risk factors for suboptimal neurodevelopment in the general population are disproportionately magnified within the CHEU population, and it is, therefore, important to draw on existing knowledge when considering the socio‐behavioural pathways through which HIV exposure could impact CHEU neurodevelopment. Approaches to identify children at greatest risk for poor outcomes and multisectoral interventions are needed to ensure optimal outcomes for CHEU in sub‐Saharan Africa.

Abstract Introduction Studies have reported a higher risk of suboptimal neurodevelopment among children who are HIV‐exposed uninfected (HEU) compared to children HIV‐unexposed uninfected (HUU). Actual academic performance among school‐aged children by HIV exposure status has not been studied. Methods Academic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana‐based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran‐Mantel‐Haenszel test. Lower academic performance was defined as a grade of “C” or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance. Results Between April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9–10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three‐drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]). Conclusions In this Botswana‐based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio‐demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.

Abstract Since short sleep duration adversely affects cardiovascular (CV) health, we investigated the effects of exposures to total sleep deprivation (TSD), and baseline (BL) and recovery (REC) sleep on CV measures. We conducted a 5‐day experiment at months 2 and 4 in two separate studies (N = 11 healthy adults; 5 females). During these repeated experiments, CV measures [stroke volume (SV), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular ejection time, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure (MAP)] were collected at three assessment time points after: (1) two BL 8 h time‐in‐bed (TIB) sleep opportunity nights; (2) a TSD night; and (3) two REC 8‐10 h TIB nights. CV measures were also collected pre‐study. TSD significantly increased SV and CI, and decreased SVRI, with large effect sizes, which importantly were reversed with recovery, indicating these measures are possible novel biomarkers for assessing the adverse consequences of TSD. Pre‐study SV, CI, SVRI, HR, SBP, and MAP measures also significantly associated with TSD CV responses at months 2 and 4 [Pearson's r: 0.615–0.862; r2: 0.378–0.743], indicating they are robust correlates of future TSD CV responses. Our novel findings highlight the critical impact of sleep on CV health across time.

Abstract Introduction Despite significant improvements in longevity and quality of life associated with antiretroviral therapy, individuals with HIV still suffer from a higher burden of sleep and circadian disruption and inflammatory‐based diseases than individuals without HIV. While melatonin is a hormone that has a role in sleep and circadian regulation and has anti‐inflammatory properties, the overnight concentration of the urinary melatonin metabolite has not yet been reported in people with HIV. Methods The aim of this study was to compare the overnight urinary melatonin metabolite levels in women aged 35–70 years with HIV (n = 151) to a well‐matched comparison group of women without HIV (n = 147). All women wore a wrist actigraphy monitor and completed daily diaries documenting sleep timing and use of medications and drugs or alcohol for 10 days. Participants collected their overnight urine near the end of the monitoring period. Results Melatonin levels did not differ between women with or without HIV, but more than 40% of women had low levels of melatonin. Higher body mass index predicted lower levels of melatonin, and lower levels of melatonin were associated with lower sleep efficiency as assessed with wrist actigraphy. Conclusion These data lay the foundation for exploration of the longitudinal consequences of endogenous melatonin levels for inflammatory‐based diseases in aging women with and without HIV. Future studies should consider the use of supplemental melatonin to improve sleep in women with lower levels of melatonin.

Interpersonal neural synchrony (INS) occurs when neural electrical activity temporally aligns between individuals during social interactions. It has been used as a metric for interpersonal closeness, often during naturalistic child-parent interactions. This study evaluated whether other biological correlates of social processing predicted the prevalence of INS during child-parent interactions, and whether their observed cooperativity modulated this association. Child-parent dyads (n = 27) performed a visuospatial tower-building task in cooperative and competitive conditions. Neural activity was recorded using mobile electroencephalogram (EEG) headsets, and experimenters coded video-recordings post-hoc for behavioral attunement. DNA methylation of the oxytocin receptor gene (OXTRm) was measured, an epigenetic modification associated with reduced oxytocin activity and socioemotional functioning. Greater INS during competition was associated with lower child OXTRm, while greater behavioral attunement during competition and cooperation was associated with higher parent OXTRm. These differential relationships suggest that interpersonal dynamics as measured by INS may be similarly reflected by other biological markers of social functioning, irrespective of observed behavior. Children’s self-perceived communication skill also showed opposite associations with parent and child OXTRm, suggesting complex relationships between children’s and their parents’ social functioning. Our findings have implications for ongoing developmental research, supporting the utility of biological metrics in characterizing interpersonal relationships.

Introduction1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle (“low-FA”) with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle (“intermediate-FA”) and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients.MethodsThis was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson’s, Spearman’s and intraclass correlation coefficients (ICC).ResultsTwenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV.ConclusionOur study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Immune checkpoints limit the activation of the immune system and serve an important homeostatic function but can also restrict immune responses against tumors. Inhibition of specific immune checkpoint proteins such as the B7:CD28 family members programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has transformed the treatment of various cancers by promoting the anti-tumor activation of immune cells. In contrast to these effects, the V-domain immunoglobulin suppressor of T-cell activation (VISTA) regulates the steady state of the resting immune system and promotes homeostasis by mechanisms distinct from PD-1 and CTLA-4. The effects of VISTA blockade have been shown to include a decrease in myeloid suppression coupled with proinflammatory changes by mechanisms that are separate and distinct from other immune checkpoint proteins; in some preclinical studies these immune effects appear synergistic. Given the potential benefits of VISTA blockade in the context of cancer therapy, the second Annual VISTA Symposium was convened virtually on September 23, 2022, to review new research from investigators and immuno-oncology experts. Discussions in the meeting extended the knowledge of VISTA biology and the effects of VISTA inhibition, particularly on cells of the myeloid lineage and resting T cells, as three candidate anti-VISTA antibodies are in, or nearing, clinical development.

ObjectiveSex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes.MethodsRetrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels.ResultsIn adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone.ConclusionEarly-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Background: People who inject drugs (PWID) are at risk for severe bacterial and fungal infections including skin and soft tissue infections, endocarditis, and osteomyelitis. PWID have high rates of self-directed discharge and are often not offered outpatient antimicrobial therapies, despite studies showing their efficacy and safety in PWID. This study fills a gap in knowledge of patient and community partner perspectives on treatment and discharge decision making for injection drug use (IDU)-associated infections. Methods: We conducted semi-structured interviews with patients ( n = 10) hospitalized with IDU-associated infections and community partners ( n = 6) in the Portland, Maine region. Community partners include peer support workers at syringe services programs (SSPs) and outreach specialists working with PWID. We transcribed and thematically analyzed interviews to explore perspectives on three domains: perspectives on long-term hospitalization, outpatient treatment options, and patient involvement in decision making. Results: Participants noted that stigma and inadequate pain management created poor hospitalization experiences that contributed to self-directed discharge. On the other hand, patients reported hospitalization provided opportunities to connect to substance use disorder (SUD) treatment and protect them from outside substance use triggers. Many patients expressed interest in outpatient antimicrobial treatment options conditional upon perceived efficacy of the treatment, perceived ability to complete treatment, and available resources and social support. Finally, both patients and community partners emphasized the importance of autonomy and inclusion in medical decision making. Although some participants acknowledged their SUD, withdrawal symptoms, or undertreated pain might interfere with decision making, they felt these medical conditions were not justification for health care professionals withholding treatment options. They recommended open communication to build trust and reduce harms. Conclusion: Patients with IDU-associated infections desire autonomy, respect, and patient-centered care from healthcare workers, and may self-discharge when needs or preferences are not met. Involving patients in treatment decisions and offering outpatient antimicrobial options may result in better outcomes. However, patient involvement in decision making may be complicated by many contextual factors unique to each patient, suggesting a need for shared decision making to meet the needs of hospitalized patients with IDU-associated infections.

Introduction: Race-, ethnicity-, and rurality-related disparities in COVID-19 vaccine uptake have been documented in the U.S. We determined whether these disparities existed among patients at the Department of Veterans Affairs, the largest healthcare system in the U.S. Methods: Using Department of Veterans Affairs Corporate Data Warehouse data, we included 5,871,438 patients (9.4% women) with at least 1 primary care visit in 2019 in a retrospective cohort study. Each patient was assigned a single race and ethnicity, which were mutually exclusive, self-reported categories. Rurality was based on the 2019 home address at the ZIP code level. Our primary outcome was time to first COVID-19 vaccination between December 15, 2020 and June 15, 2021. Additional covariates included age (in years), sex, geographic region (North Atlantic, Midwest, Southeast, Pacific, continental), smoking status (current, former, never), Charlson Comorbidity Index (based on ≥1 inpatient or 1 outpatient International Classification of Diseases codes), service connection (any/none, using standardized Department of Veterans Affairs cut offs for disability compensation), and influenza vaccination in 2019–2020 (yes/no). Results: Compared with unvaccinated patients, those vaccinated (n=3,238,532; 55.2%) were older (mean age in years vaccinated=66.3 [SD=14.4] vs unvaccinated=57.7 [18.0], p

Abstract Thousands of colonoscopies were canceled during the initial surge of the COVID‐19 pandemic. As facilities resumed services, some patients were hesitant to reschedule. The purpose of this study was to determine whether a decision aid plus telephone coaching would increase colorectal cancer (CRC) screening and improve patient reports of shared decision making (SDM). A randomized controlled trial assigned adults aged 45–75 without prior history of CRC who had a colonoscopy canceled from March to May 2020 to intervention (n = 400) or usual care control (n = 400) arms. The intervention arm received three‐page decision aid and call from decision coach from September 2020 through November 2020. Screening rates were collected at 6 months. A subset (n = 250) in each arm was surveyed 8 weeks after randomization to assess SDM (scores range 0–4, higher scores indicating more SDM), decisional conflict, and screening preference. The sample was on average, 60 years old, 53% female, 74% White, non‐Hispanic, and 11% Spanish speaking. More intervention arm patients were screened within 6 months (35% intervention vs 23% control, p

Abstract Kidney allograft survival remains poorer in Black compared to White recipients due to racial differences in calcineurin inhibitor (CNI) pharmacology. P‐glycoprotein (P‐gp), an ABC efflux transporter expressed in peripheral blood mononuclear cells (PBMCs), modulates CNI pharmacokinetics and intracellular pharmacology. This study investigated P‐gp function in PBMC ex vivo at 0 (trough), 4, 8, and 12 h in stable Black and White male and female kidney transplant recipients (n = 67) receiving tacrolimus and mycophenolic acid. Tacrolimus doses were adjusted to troughs of 4–10 ng/ml. P‐gp function was quantified with flow cytometric measurement of cyclosporine (CYA; 2.5 μM)‐reversible efflux of P‐gp substrate, 3,3′‐Diethyloxacarbocyanine iodide by determining the percentage change of mean fluorescent intensity (MFI) with CYA (% ΔMFI). The composite parameter of area under the concentration versus time (AUC)0–12h % ΔMFI estimated P‐gp function. Data analysis examined race, sex, and race‐sex associations to P‐gp function. A secondary aim analyzed ABCB1 genotypes: 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), and P‐gp function. P‐gp function (% ΔMFI) was higher in White patients at troughs (p = 0.031) compared to Black counterparts with similar trends at 4 and 8 h. Reduced AUC0–12h % ΔMFI was noted in Black recipients (N = 32) compared with Whites (N = 35, p = 0.029) with notable pairwise adjusted differences between Black and White women (p = 0.021). Higher AUC0–12h % ΔMFI was associated with ABCB1 2677 TT compared to GG variants (p = 0.035). The AUC0–12h % ΔMFI was greater in White than Black subjects. P‐gp function was higher at troughs in White subjects and differed between race‐sex groups. P‐gp function in PBMC may influence intracellular tacrolimus exposure and inter‐relating pharmacodynamic responses which may support race and sex pharmacologic differences.

Abstract Background Climate change is warming the Arctic faster than the rest of the planet. Shifts in whale migration timing have been linked to climate change in temperate and sub-Arctic regions, and evidence suggests Bering–Chukchi–Beaufort (BCB) bowhead whales (Balaena mysticetus) might be overwintering in the Canadian Beaufort Sea. Methods We used an 11-year timeseries (spanning 2009–2021) of BCB bowhead whale presence in the southern Chukchi Sea (inferred from passive acoustic monitoring) to explore relationships between migration timing and sea ice in the Chukchi and Bering Seas. Results Fall southward migration into the Bering Strait was delayed in years with less mean October Chukchi Sea ice area and earlier in years with greater sea ice area (p = 0.04, r2 = 0.40). Greater mean October–December Bering Sea ice area resulted in longer absences between whales migrating south in the fall and north in the spring (p

Abstract Democracies around the world face the threat of manipulation of their electorates via coordinated online influence campaigns. Researchers have responded by developing valuable methods for finding automated accounts and identifying false information, but these valiant efforts often fall into a cat-and-mouse game with perpetrators who constantly change their behavior. This has forced several researchers to go beyond the detection of individual malicious actors by instead identifying the coordinated activity that propels potent information operations. In this vein, we provide rigorous quantitative evidence for the notion that sudden increases in Twitter account creations may provide early warnings of online information operations. Analysis of fourteen months of tweets discussing the 2020 U.S. elections revealed that accounts created during bursts exhibited more similar behavior, showed more agreement on mail-in voting and mask wearing, and were more likely to be bots and share links to low-credibility sites. In concert with other techniques for detecting nefarious activity, social media platforms could temporarily limit the influence of accounts created during these bursts. Given the advantages of combining multiple anti-misinformation methods, we join others in presenting a case for the need to develop more integrable methods for countering online influence campaigns.

The purpose of this project was to evaluate whether screening positive on obstructive sleep apnea questionnaires in the first trimester of pregnancy was associated with miscarriage. This was a secondary analysis of a prospective observational cohort study of participants who were screened for sleep apnea during pregnancy with the Epworth Sleepiness Scale, Berlin Questionnaire, and novel items related to sleep and napping. This secondary analysis was IRB exempt. Our primary outcome was miscarriage in the index pregnancy. An association between responses to the sleep apnea screening questions with miscarriage of the index pregnancy was queried via Poisson regression. We found that gravidae who had elevated scores on both the Epworth Sleepiness Scale and the Berlin Questionnaire were more likely to experience miscarriage than those who had elevated scores on only one questionnaire or neither (p = 0.018). Gravidae who reported snoring (p = 0.042) or hypertension (p = 0.013) in the first trimester were more likely to experience miscarriage than gravidae who did not. Gravidae who reported napping in the first trimester were less likely to experience miscarriage (p = 0.045), even after adjusting for confounding variables (p = 0.007). In conclusion, we found that screening positive on both the Berlin Questionnaire and Epworth Sleepiness Scale was statistically significantly associated with miscarriage prior to adjustment for confounding variables, as did snoring and hypertension. After adjusting for confounding variables, only not napping was associated with miscarriage. Given the small sample size, further investigation into this topic is warranted.

Data science techniques are powerful tools for extracting knowledge from large datasets. Analyzing the job market by classifying online job advertisements (ads) has recently received much attention. Various approaches for multi-label classification (e.g., self-supervised learning and clustering) have been developed to identify the occupation from a job advertisement and have achieved a satisfying performance. However, these approaches require labeled datasets with hundreds of thousands of examples and focus on specific databases such as the Occupational Information Network (O*NET) that are more adapted to the US job market. In this paper, we present a two-stage job title identification methodology to address the case of small datasets. We use Bidirectional Encoder Representations from Transformers (BERT) to first classify the job ads according to their corresponding sector (e.g., Information Technology, Agriculture). Then, we use unsupervised machine learning algorithms and some similarity measures to find the closest matching job title from the list of occupations within the predicted sector. We also propose a novel document embedding strategy to address the issues of processing and classifying job ads. Our experimental results show that the proposed two-stage approach improves the job title identification accuracy by 14% to achieve more than 85% in some sectors. Moreover, we found that incorporating document embedding-based approaches such as weighting strategies and noise removal improves the classification accuracy by 23.5% compared to approaches based on the Bag of words model. Further evaluations verify that the proposed methodology either outperforms or performs at least as well as the state-of-the-art methods. Applying the proposed methodology to Moroccan job market data has helped identify emerging and high-demand occupations in Morocco.

Abstract Background Racehorses commonly develop evidence of mild asthma in response to dust exposure. Diets deficient in omega‐3 polyunsaturated fatty acids (Ω‐3) might exacerbate this response. Hypothesis To compare dust exposure, bronchoalveolar lavage fluid (BALF) cytology, and plasma Ω‐3 and specialized pro‐resolving mediators (SPM) concentrations amongst racehorses fed dry hay, steamed hay, and haylage. Animals Forty‐three Thoroughbred racehorses. Methods Prospective clinical trial. Horses were randomly assigned to be fed dry hay, steamed hay, or haylage for 6 weeks. Measures of exposure to dust in the breathing zone were obtained twice. At baseline, week‐3, and week‐6, BALF cytology was examined. Plasma lipid profiles and plasma SPM concentrations were examined at baseline and week 6. Generalized linear mixed models examined the effect of forage upon dust exposure, BALF cytology, Ω‐3, and SPM concentrations. Results Respirable dust was significantly higher for horses fed hay (least‐square mean ± s.e.m. 0.081 ± 0.007 mg/m3) when compared with steamed hay (0.056 ± 0.005 mg/m3, P = .01) or haylage (0.053 ± 0.005 mg/m3, P

Erickson et al. compare OXTR DNA methylation in individuals who experienced a postpartum hemorrhage arising from uterine atony and matched controls. Those with higher OXTR DNA methylation required more oxytocin during parturition and had a higher risk of postpartum hemorrhage.

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

Abstract Social media has provided a citizen voice, giving rise to grassroots collective action, where users deploy a concerted effort to disseminate online narratives and even carry out offline protests. Sometimes these collective action are aided by inorganic synchronization, which arise from bot actors. It is thus important to identify the synchronicity of emerging discourse on social media and the indications of organic/inorganic activity within the conversations. This provides a way of profiling an event for possibility of offline protests and violence. In this study, we build on past definitions of synchronous activity on social media— simultaneous user action–and develop a Combined Synchronization Index (CSI) which adopts a hierarchical approach in measuring user synchronicity. We apply this index on six political and social activism events on Twitter and analyzed three action types: synchronicity by hashtag, URL and @mentions.The CSI provides an overall quantification of synchronization across all action types within an event, which allows ranking of a spectrum of synchronicity across the six events. Human users have higher synchronous scores than bot users in most events; and bots and humans exhibits the most synchronized activities across all events as compared to other pairs (i.e., bot-bot and human-human). We further rely on the harmony and dissonance of CSI-Network scores with network centrality metrics to observe the presence of organic/inorganic synchronization. We hope this work aids in investigating synchronized action within social media in a collective manner.

Abstract Background Genome wide association (GWA) studies demonstrate linkages between genetic variants and traits of interest. Here, we tested associations between single nucleotide polymorphisms (SNPs) in rice (Oryza sativa) and two root hair traits, root hair length (RHL) and root hair density (RHD). Root hairs are outgrowths of single cells on the root epidermis that aid in nutrient and water acquisition and have also served as a model system to study cell differentiation and tip growth. Using lines from the Rice Diversity Panel-1, we explored the diversity of root hair length and density across four subpopulations of rice (aus, indica, temperate japonica, and tropical japonica). GWA analysis was completed using the high-density rice array (HDRA) and the rice reference panel (RICE-RP) SNP sets. Results We identified 18 genomic regions related to root hair traits, 14 of which related to RHD and four to RHL. No genomic regions were significantly associated with both traits. Two regions overlapped with previously identified quantitative trait loci (QTL) associated with root hair density in rice. We identified candidate genes in these regions and present those with previously published expression data relevant to root hair development. We re-phenotyped a subset of lines with extreme RHD phenotypes and found that the variation in RHD was due to differences in cell differentiation, not cell size, indicating genes in an associated genomic region may influence root hair cell fate. The candidate genes that we identified showed little overlap with previously characterized genes in rice and Arabidopsis. Conclusions Root hair length and density are quantitative traits with complex and independent genetic control in rice. The genomic regions described here could be used as the basis for QTL development and further analysis of the genetic control of root hair length and density. We present a list of candidate genes involved in root hair formation and growth in rice, many of which have not been previously identified as having a relation to root hair growth. Since little is known about root hair growth in grasses, these provide a guide for further research and crop improvement.

Anxiety is common during the antepartum, intrapartum, and postpartum period. While the relationship between obstetric pain and depression is well characterized, there are few publications examining the relationship between obstetric pain and anxiety. Our objective was to characterize the association, if any, between postpartum pain and anxiety. This was a survey-based cross-sectional study. The general anxiety disorder (GAD)-7 and American Pain Society patient outcome questionnaire (APS-POQ) were completed by 64 postpartum participants at hospital discharge. Associations between anxiety and pain control were assessed. Participants with moderate to severe scores (greater or equal to 10) on the GAD-7 had more maximum pain scores (0 to 10 scale) in the severe range (greater or equal to 7) in the first (p = 0.049) and second (p = 0.010) 24 h periods after delivery and were more likely to have spent more time in severe pain within these time frames (p = 0.007 and p = 0.010, respectively). Similar relationships were observed when classifying anxiety ordinally. In conclusion, higher postpartum pain scores were associated with greater anxiety in the postpartum period.

Abstract Background Physician delivered weight management counseling (WMC) occurs infrequently and physicians report lack of training and poor self-efficacy. The purpose of this study was to develop and test the Video-based Communication Assessment (VCA) for weight management counseling (WMC) training in medical residents. Methods This study was a mixed methods pilot conducted in 3 phases. First, we created five vignettes based on our prior data and expert feedback, then administered the vignettes via the VCA to Internal Medicine categorical residents (n = 16) from a University Medical School. Analog patients rated responses and also provided comments. We created individualized feedback reports which residents were able to view on the VCA. Lastly, we conducted debriefing interviews with the residents (n = 11) to obtain their feedback on the vignettes and personalized feedback. Interviews were transcribed, and we used thematic analysis to generate and apply codes, followed by identifying themes. Results Descriptive statistics were calculated and learning points were created for the individualized feedback reports. In VCA debriefing interviews with residents, five themes emerged: 1) Overall the VCA was easy to use, helpful and more engaging than traditional learning and assessment modes, 2) Patient scenarios were similar to those encountered in the clinic, including diversity, health literacy and different stages of change, 3) The knowledge, skills, and reminders from the VCA can be transferred to practice, 4) Feedback reports were helpful, to the point and informative, including the exemplar response of how to best respond to the scenario, and 5) The VCA provide alternatives and practice scenarios to real-life patient situations when they aren’t always accessible. Conclusions We demonstrated the feasibility and acceptability of the VCA, a technology delivered platform, for delivering WMC to residents. The VCA exposed residents to diverse patient experiences and provided potential opportunities to tailor providers responses to sociological and cultural factors in WMC scenarios. Future work will examine the effect of the VCA on WMC in actual clinical practice.

The COVID-19 pandemic revealed ways in which communities take care of themselves in deeply unequal times. Tracing a pandemic-year evolution of community-based organizations (CBOs) in the San Francisco Bay Area through twenty-seven semi-structured interviews with CBO staff, we argue that, through diverse approaches that we characterize as a politics of care, Bay Area CBOs are reshaping their work in ways that could address social and structural determinants of health inequities in the long term. Their approaches call for rethinking the crisis framework around public health challenges such as pandemics. Our research confirms that, rather than an exceptional, short-term challenge, the pandemic crisis is a product of a longer trajectory of structurally produced inequities endemic to racial capitalism.

Abstract Infants with congenital diaphragmatic hernia (CDH) may require cardiopulmonary bypass and systemic anticoagulation. Expeditious lung growth while on bypass is essential for survival. Previously, we demonstrated that heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). We investigated the effects of the direct thrombin inhibitors (DTIs) bivalirudin and argatroban. In vitro assays of lung endothelial cell proliferation and apoptosis were performed. C57BL/6 J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were pre-loaded with normal saline (control), bivalirudin, argatroban, or heparin and outcomes were assessed on postoperative day 8. Heparin administration inhibited endothelial cell proliferation in vitro and significantly decreased lung volume in vivo, while bivalirudin and argatroban preserved lung growth. These findings correlated with changes in alveolarization on morphometric analysis. Treadmill exercise tolerance testing demonstrated impaired exercise performance in heparinized mice; bivalirudin/argatroban did not affect exercise tolerance. On lung protein analysis, heparin decreased angiogenic signaling which was not impacted by bivalirudin or argatroban. Together, this data supports the use of DTIs as alternatives to heparin for systemic anticoagulation in CDH patients on bypass. Based on this work, clinical studies on the impact of heparin and DTIs on CDH outcomes are warranted.

Abstract Background With an aging population, rising incidence of breast cancer, improved survival rates, and obesity epidemic, there will be a growing population of older adult breast cancer survivors with obesity. This complex population, often with multimorbidity, is at risk for several poor health outcomes, including recurrence, cardiovascular disease, dementia, and diabetes, and a number of deleterious symptoms, including a worsened inflammatory profile, breast cancer‐ related lymphedema, mobility disability, cognitive impairment, anxiety, and depressive symptoms. A wealth of meta‐analytic and randomized controlled trial evidence show that adherence to World Health Organization and 2018 United States Physical Activity guidelines‐based levels of moderate‐to‐vigorous physical activity (MVPA) reduces risk of all‐cause mortality, and improves symptoms. However, few survivors engage in recommended levels of MVPA, and symptoms related to their multimorbidity may preclude engaging in sufficient levels of MVPA. Additional research of MVPA in this population is warranted; however, understudied light‐intensity physical activity (LIPA) may be a more pragmatic target than MVPA among this complex population facing extensive challenges meeting MVPA recommendations. Large benefits are likely to occur from increasing these survivors' total activity, and LIPA prescriptions may be a more pragmatic approach than MVPA to aid this transition. Methods We present a broad, narrative review of the evidence for MVPA and LIPA in this population on an array of health outcomes across the translational science spectrum (clinical, implementation, and public health), and identify a number of directions for future research focused on understanding the potential diverse health effects of LIPA. Conclusion Additional LIPA research is warranted, as LIPA prescriptions may be a pragmatic strategy to effectively promote physical activity to this complex population.

Abstract Objective Rural veterans have high obesity rates. Yet, little is known about this population's engagement with the Veterans Affairs (VA) weight management program (MOVE!). The study objective is to determine whether MOVE! enrollment, anti‐obesity medication use, bariatric surgery use, retention, and outcomes differ by rurality for veterans with severe obesity. Methods This is a retrospective cohort study using Veterans Health Administration patient databases, including VA patients with severe obesity during 2015–2017. Patients were categorized using Rural‐Urban Commuting Area codes. Primary outcomes included proportion of patients and risk‐adjusted likelihood of initiating VA MOVE!, anti‐obesity medication, or bariatric surgery and risk‐adjusted highly rural|Hazard Ratio (HR) of any obesity treatment. Secondary outcomes included treatment retention (≥12 weeks) and successful weight loss (5%) among patients initiating MOVE!, and risk‐adjusted odds of retention and successful weight loss. Results Among 640,555 eligible veterans, risk‐adjusted relative likelihood of MOVE! treatment was significantly lower for rural and HR veterans (HR = 0.83, HR = 0.67, respectively). Initiation rates of anti‐obesity medication use were significantly lower as well, whereas bariatric surgery rates, retention, and successful weight loss did not differ. Conclusions Overall treatment rates with MOVE!, bariatric surgery, and anti‐obesity medications remain low. Rural veterans are less likely to enroll in MOVE! and less likely to receive anti‐obesity medications than urban veterans.

Arctic vegetation communities are rapidly changing with climate warming, which impacts wildlife, carbon cycling, and climate feedbacks. Accurately monitoring vegetation change is thus crucial, but scale mismatches between field and satellite-based monitoring cause challenges. Remote sensing from unmanned aerial vehicles (UAVs) has emerged as a bridge between field data and satellite-based mapping. We assessed the viability of using high-resolution UAV imagery and UAV-derived Structure from Motion to predict cover, height, and aboveground biomass (henceforth biomass) of Arctic plant functional types (PFTs) across a range of vegetation community types. We classified imagery by PFT, estimated cover and height, and modeled biomass from UAV-derived volume estimates. Predicted values were compared to field estimates to assess results. Cover was estimated with a root-mean-square error (RMSE) of 6.29%–14.2%, and height was estimated with an RMSE of 3.29–10.5 cm depending on the PFT. Total aboveground biomass was predicted with an RMSE of 220.5 g m−2, and per-PFT RMSE ranged from 17.14 to 164.3 g m−2. Deciduous and evergreen shrub biomass was predicted most accurately, followed by lichen, graminoid, and forb biomass. Our results demonstrate the effectiveness of using UAVs to map PFT biomass, which provides a link towards improved mapping of PFTs across large areas using earth observation satellite imagery.

This article explores the historical and lingering effects of US government involvement in defining Islam as public and foreign policy. It focuses on the Islam Centennial 14, a US program to celebrate the fourteenth centennial of Islam – and manage the US’s global image – which was active in the late 1970s and early 1980s. The Islam Centennial 14 organized a nationally touring museum exhibit, distributed information on Islam to partners and public schools, produced a newsletter, documentaries, and speaker series on Islam. It also culminated in one of the first academic centers in the US devoted to the study of Islam. The Islam Centennial 14’s activities provided a counter-narrative to rising Islamophobia and anti-Arab sentiment, while the discourses that swirled around them – including their own press reports, outside conspiracy theories, and academic analyses – foreshadowed more contemporary xenophobic politics. This article presents the Islam Centennial 14 specifically as a case study through which to consider the workings and ramifications of American Islamophilia. It examines how such celebrations of Islam as part and parcel of international and national governance reinscribe both racialized representations of Islam and, however inadvertently, anti-Muslim sentiments. It argues that Islamophilia is an undertheorized corollary to more explicit anti-Muslim positions, and one whose deployment and effects more than merit sustained attention.

The neoliberal trend in spatial planning seemingly causes the loss of control of spatial plans for destination developments in the mountain regions of southern Norway. The predominant local discourse, as seen in local newspapers and other media, was originally positive to the development of second homes. Changes in development plans have, as in the Skeikampen-destination case, incited strong counter-discourses based on concerns for pasture rights, nature values, and access, in addition to sustainability in general. These discourses create a perception of reality in stark contrast to the central- government discourse, as found in the plan and building act, and governmental documents.

The number of hotels in the mountains of south-eastern Norway has decreased over the last three decades, with a concurrent increase in the number of modern, privately-owned second homes. The growth of second-home villages and associated commercial activity has produced sustainability issues. The shift in the planning and development process from the local government to private developers has resulted in a piece-by-piece process with the loss of sight of long-term consequences. This short review discusses the causes of uncontrolled or poor planning of mountain regions; in particular, the neoliberal trend in physical planning and the problem of small local communities.

Abstract Background Postpartum hemorrhage remains a key contributor to overall maternal morbidity in the United States. Current clinical assessment methods used to predict postpartum hemorrhage are unable to prospectively identify about 40% of hemorrhage cases. Oxytocin is a first-line pharmaceutical for preventing and treating postpartum hemorrhage, which acts through oxytocin receptors on uterine myocytes. Existing research indicates that oxytocin function is subject to variation, influenced in part by differences in the DNA sequence within the oxytocin receptor gene. One variant, rs53576, has been shown to be associated with variable responses to exogenous oxytocin when administered during psychological research studies. How this variant may influence myometrial oxytocin response in the setting of third stage labor has not been studied. We tested for differences in the frequency of the oxytocin receptor genotype at rs53576 in relationship to the severity of blood loss among a sample of individuals who experienced vaginal birth. Methods A case–control prospective design was used to enroll 119 postpartum participants who underwent vaginal birth who were at least 37 weeks of gestation. Cases were defined by either a 1000 mL or greater blood loss or instances of heavier bleeding where parturients were given additional uterotonic treatment due to uterine atony. Controls were matched to cases on primiparity and labor induction status. Genotype was measured from a maternal blood sample obtained during the 2nd postpartum month from 95 participants. Statistical analysis included bivariate tests and generalized linear and Poisson regression modeling. Results The distribution of the genotype across the sample of 95 participants was 40% GG (n = 38), 50.5% AG (n = 48) and 9.5% AA (n = 9). Blood loss of 1000 mL or greater occurred at a rate of 7.9% for GG, 12.5% for AG and 55.6% for AA participants (p = 0.005). Multivariable models demonstrated A-carriers (versus GG) had 275.2 mL higher blood loss (95% CI 96.9–453.4, p