Short-Stay Units vs Routine Admission From the Emergency Department in Patients With Acute Heart Failure: The SSU-AHF Randomized Clinical Trial.

Importance: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. Objective: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. Design, Setting, and Participants: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. Intervention: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. Main Outcomes and Measures: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. Results: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. Conclusions and Relevance: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. Trial Registration: ClinicalTrials.gov Identifier: NCT03302910.

Longitudinal associations between psychedelic use and meditation practices in the United States and the United Kingdom.

BACKGROUND: Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation. METHODS: Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice. RESULTS: The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = -0.29, p = 0.037). CONCLUSIONS: Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.

Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial.

Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, Setting, and Participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, ß-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main Outcome Measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and Relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03412201.

Environmental neurology: Concepts and short history of an interdisciplinary approach to etiology, treatment and prevention.

Environmental Neurology (EN), a sub-discipline of Neurology and Neurological Sciences, favors an interdisciplinary collaboration allowing a holistic approach to understanding the impact of environmental factors on the nervous system and their relationship with neurological diseases. Several examples of diseases and conditions show the large scope of subjects addressed by EN. The EN sub-discipline focuses on both individual and population issues thus joining patient care and public health, respectively. Neuropathogenesis is addressed by several major questions: How do the environment and nervous system interact? Which exogenous factors can trigger neurological disease? When, where and how do they act? What are the therapeutic implications, and how can these disorders be controlled or prevented. To answer such questions, we address the incentive for, philosophy of and methods developed by EN, which seeks to safeguard Brain Health and, thus, the quality of life.

Classic psychedelic use and current meditation practice.

Objectives: Previous research has investigated potential synergies between classic psychedelics and meditation practice, but relatively little remains known about the relationship between classic psychedelic experiences and engagement with meditation practice.The purpose of this study was to investigate associations between classic psychedelic experiences and engagement with two popular types of meditation: mindfulness meditation and loving-kindness or compassion meditation. Methods: This retrospective, population-based observational study included 2,822 respondents aged 18 years or older in the United States. Using covariate-adjusted regression models, this study examined associations of classic psychedelic experiences with current practice of mindfulness meditation and loving-kindness or compassion meditation. Results: In covariate-adjusted regression models, lifetime classic psychedelic use was associated with a higher frequency of current mindfulness meditation practice but not current loving-kindness or compassion meditation practice. Both psychological insight and "ego dissolution" were associated with a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice. Notably, when psychological insight and "ego dissolution" were entered into the regression model simultaneously, only greater psychological insight was associated with having a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice. Conclusion: Although the findings in this study cannot demonstrate causality, they suggest that classic psychedelic experiences may exert a positive effect on the cultivation and maintenance of health-related behaviors such as regular meditation practice, with psychological insight appearing to be a stronger predictor than "ego dissolution." Preregistration: This study was not preregistered.

Association between soil organic carbon and calcium in acidic grassland soils from Point Reyes National Seashore, CA.

Organo-mineral and organo-metal associations play an important role in the retention and accumulation of soil organic carbon (SOC). Recent studies have demonstrated a positive correlation between calcium (Ca) and SOC content in a range of soil types. However, most of these studies have focused on soils that contain calcium carbonate (pH > 6). To assess the importance of Ca-SOC associations in lower pH soils, we investigated their physical and chemical interaction in the grassland soils of Point Reyes National Seashore (CA, USA) at a range of spatial scales. Multivariate analyses of our bulk soil characterisation dataset showed a strong correlation between exchangeable Ca (CaExch; 5-8.3 c.molc kg-1) and SOC (0.6-4%) content. Additionally, linear combination fitting (LCF) of bulk Ca K-edge X-ray absorption near-edge structure (XANES) spectra revealed that Ca was predominantly associated with organic carbon across all samples. Scanning transmission X-ray microscopy near-edge X-ray absorption fine structure spectroscopy (STXM C/Ca NEXAFS) showed that Ca had a strong spatial correlation with C at the microscale. The STXM C NEXAFS K-edge spectra indicated that SOC had a higher abundance of aromatic/olefinic and phenolic C functional groups when associated with Ca, relative to C associated with Fe. In regions of high Ca-C association, the STXM C NEXAFS spectra were similar to the spectrum from lignin, with moderate changes in peak intensities and positions that are consistent with oxidative C transformation. Through this association, Ca thus seems to be preferentially associated with plant-like organic matter that has undergone some oxidative transformation, at depth in acidic grassland soils of California. Our study highlights the importance of Ca-SOC complexation in acidic grassland soils and provides a conceptual model of its contribution to SOC preservation, a research area that has previously been unexplored. Supplementary Information: The online version contains supplementary material available at 10.1007/s10533-023-01059-2.

Modified rice bran arabinoxylan as a nutraceutical in health and disease-A scoping review with bibliometric analysis.

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English (MEDLINE, ProQuest, CENTRAL, Emcare, CINAHL+, Web of Science), Japanese (CiNii, J-Stage), Korean (KCI, RISS, ScienceON), and Chinese (CNKI, Wanfang) sources while combining bibliometrics and network analyses for data visualisation. Searches were conducted between September and October 2022. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median = 3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). Over 50% of the research was from the USA (29/98, 29.59%) and Japan (22/98, 22.45%). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. As an oral supplement taken as an adjuvant during chemoradiotherapy, cancer patients reported reduced side effects and improved quality of life in human studies, indicating RBAC's impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Self-care treatment for lymphoedema of lymphatic filariasis using integrative medicine.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease presenting mainly as lymphoedema (elephantiasis). At present, LF is not effectively treated. Integrative medicine (IM) treatment for lymphoedema uses a combination of Indian traditional medicine, Ayurveda, alongside yoga exercises, compression therapy, antibiotics and antifungal treatments, providing a useful combination where resources are limited and different practices are in use. OBJECTIVES: To assess the effectiveness of the IM in the existing clinical practice of lower-limb lymphoedema management and to determine whether the treatment outcomes align with the World Health Organization (WHO) global goal of LF management. METHODS: Institutional data from electronic medical records of all 1698 patients with LF between 2010 and 2019 were retrospectively analysed using pre- and post-treatment comparisons and the National Institute for Health and Care Excellence guidelines for clinical audit. The primary treatment outcomes evaluated were limb volume, bacterial entry points (BEEPs), episodes of cellulitis, and health-related quality of life (HRQoL). Secondary outcomes included the influence of the patient's sex, duration of illness, education and employment status on volume reduction. Multiple regression analysis, t-test, χ2-test, analysis of variance, Mann-Whitney U-test and the Kruskal-Wallis test were used to assess the association between IM and patients' treatment outcomes. RESULTS: Limb volume reduced by 24.5% [95% confidence interval (CI) 22.47-26.61; n = 1660] following an intensive supervised care period (mean 14.84 days, n = 1660). Limb volume further reduced by 1.42% (95% CI 0.76-2.07; n = 1259) at the first follow-up visit (mean 81.45 days), and by 2.3% between the first and second follow-up visits (mean 231.32 days) (95% CI 1.26-3.34; n = 796). BEEPs were reduced upon follow-up; excoriations (78.4%) and intertrigo (26.7%) were reduced at discharge and further improvements was achieved at the follow-up visits. In total, 4% of patients exhibited new BEEPs at the first follow-up [eczema (3.9%), folliculitis (6.5%), excoriations (11.9%) and intertrigo (15.4%); 4 of 7 BEEPs were recorded]. HRQoL, measured using the disease-specific Lymphatic Filariasis Specific Quality of Life Questionnaire, showed an average score of 73.9 on admission, which increased by 17.8 at the first follow-up and 18.6 at the second follow-up. No patients developed new cellulitis episodes at the first follow-up, and only five patients (5.3%) developed new episodes of cellulitis at the second follow-up. CONCLUSIONS: IM for lower-limb lymphoedema successfully reduces limb volume and episodes of cellulitis, and also reduces BEEPs, leading to improved HRQoL. IM aligns with the LF treatment goals of the WHO and is a low-cost, predominantly self-care management protocol. IM has the potential to change care models and improve the lives of patients with lymphoedema.

Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol.

INTRODUCTION: Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life. METHODS AND ANALYSIS: 'D-Kids' is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother-infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The sample size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups. ETHICS AND DISSEMINATION: This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001174279.

Late-life Rapamycin Treatment Enhances Cardiomyocyte Relaxation Kinetics and Reduces Myocardial Stiffness.

Diastolic dysfunction is a key feature of the aging heart. We have shown that late-life treatment with mTOR inhibitor, rapamycin, reverses age-related diastolic dysfunction in mice but the molecular mechanisms of the reversal remain unclear. To dissect the mechanisms by which rapamycin improves diastolic function in old mice, we examined the effects of rapamycin treatment at the levels of single cardiomyocyte, myofibril and multicellular cardiac muscle. Compared to young cardiomyocytes, isolated cardiomyocytes from old control mice exhibited prolonged time to 90% relaxation (RT 90 ) and time to 90% Ca 2+ transient decay (DT 90 ), indicating slower relaxation kinetics and calcium reuptake with age. Late-life rapamycin treatment for 10 weeks completely normalized RT 90 and partially normalized DT 90 , suggesting improved Ca 2+ handling contributes partially to the rapamycin-induced improved cardiomyocyte relaxation. In addition, rapamycin treatment in old mice enhanced the kinetics of sarcomere shortening and Ca 2+ transient increase in old control cardiomyocytes. Myofibrils from old rapamycin-treated mice displayed increased rate of the fast, exponential decay phase of relaxation compared to old controls. The improved myofibrillar kinetics were accompanied by an increase in MyBP-C phosphorylation at S282 following rapamycin treatment. We also showed that late-life rapamycin treatment normalized the age-related increase in passive stiffness of demembranated cardiac trabeculae through a mechanism independent of titin isoform shift. In summary, our results showed that rapamycin treatment normalizes the age-related impairments in cardiomyocyte relaxation, which works conjointly with reduced myocardial stiffness to reverse age-related diastolic dysfunction.

Changes in the Human Gut Microbiome during Dietary Supplementation with Modified Rice Bran Arabinoxylan Compound.

This study investigated the effects of a modified rice bran arabinoxylan compound (RBAC) as a dietary supplement on the gut microbiota of healthy adults. Ten volunteers supplemented their diet with 1 g of RBAC for six weeks and 3 g of RBAC for another six weeks, with a three-week washout period. Faecal samples were collected every 3 weeks over 21 weeks. Microbiota from faecal samples were profiled using 16S rRNA sequencing. Assessment of alpha and beta microbiota diversity was performed using the QIIME2 platform. The results revealed that alpha and beta diversity were not associated with the experimental phase, interventional period, RBAC dosage, or time. However, the statistical significance of the participant was detected in alpha (p < 0.002) and beta (weighted unifrac, p = 0.001) diversity. Explanatory factors, including diet and lifestyle, were significantly associated with alpha (p < 0.05) and beta (p < 0.01) diversity. The individual beta diversity of six participants significantly changed (p < 0.05) during the interventional period. Seven participants showed statistically significant taxonomic changes (ANCOM W ≥ 5). These results classified four participants as responders to RBAC supplementation, with a further two participants as likely responders. In conclusion, the gut microbiome is highly individualised and modulated by RBAC as a dietary supplement, dependent on lifestyle and dietary intake.

Wildfire immediately reduces nest and adult survival of greater sage-grouse.

Wildfire events are becoming more frequent and severe on a global scale. Rising temperatures, prolonged drought, and the presence of pyrophytic invasive grasses are contributing to the degradation of native vegetation communities. Within the Great Basin region of the western U.S., increasing wildfire frequency is transforming the ecosystem toward a higher degree of homogeneity, one dominated by invasive annual grasses and declining landscape productivity. Greater sage-grouse (Centrocercus urophasianus; hereafter sage-grouse) are a species of conservation concern that rely on large tracts of structurally and functionally diverse sagebrush (Artemisia spp.) communities. Using a 12-year (2008-2019) telemetry dataset, we documented immediate impacts of wildfire on demographic rates of a population of sage-grouse that were exposed to two large wildfire events (Virginia Mountains Fire Complex-2016; Long Valley Fire-2017) near the border of California and Nevada. Spatiotemporal heterogeneity in demographic rates were accounted for using a Before-After Control-Impact Paired Series (BACIPS) study design. Results revealed a 40% reduction in adult survival and a 79% reduction in nest survival within areas impacted by wildfires. Our results indicate that wildfire has strong and immediate impacts to two key life stages of a sagebrush indicator species and underscores the importance of fire suppression and immediate restoration following wildfire events.

Legal medicine implications of a multidisciplinary approach to managing Traumatic Encephalopathy Syndrome in Australia.

The medical profession has a fundamental obligation to accurately diagnose and effectively treat a range of diseases and conditions. In the case of Traumatic Encephalopathy Syndrome (TES), where there are no universally accepted clinical diagnostic criteria, a clear clinical diagnosis can pose significant challenges for healthcare providers and for subsequent appropriate management. "Nihilism" or an uncertain working diagnosis is not acceptable in the medical field and deserves further consideration. This paper explores the legal obligations that are placed upon healthcare professionals, both individually and as a part of a multidisciplinary team. This article analyses the responsibilities and expectations of medical professionals in diagnosing and treating complex medical conditions, such as TES. The authors address legal issues that must be considered for an effective operation of integrated medicine to enhance the overall quality of care and improving patient outcomes for those affected with underlying Chronic Traumatic Encephalopathy (CTE).

Altered states of leadership: mindfulness meditation, psychedelic use, and leadership development.

Background: Previous research suggests that mindfulness meditation and psychedelic substances show promise as mental health interventions, but relatively little remains known about their potential impact on leadership outcomes. Aims: This study aimed to investigate if and how mindfulness meditation and psychedelic use may impact leadership among respondents with a management position as their primary role at work. Methods: Using samples representative of the US and UK adult populations with regard to sex, age, and ethnicity, this study used quantitative and qualitative methods to examine if and how mindfulness meditation and psychedelic use may impact leadership. Results: Among respondents with a management position as their primary role at work (n = 3,150), 1,373 reported having tried mindfulness meditation and 559 reported having tried psychedelics. In covariate-adjusted regression analyses, both lifetime number of hours of mindfulness meditation practice and greater psychological insight during respondents' most intense psychedelic experience were associated with describing a positive impact on leadership (ORs = 2.33, 3.49; ps < 0.001), while qualitative analyses revealed nuances in the type of impacts mindfulness meditation and psychedelic use had on leadership. There were several subthemes (e.g., focus, creativity, patience, empathy, compassion) that were frequently reported with both mindfulness meditation and psychedelic use. There were also unique subthemes that were more commonly reported with mindfulness meditation (e.g., improved sleep, stress reduction, calming effects) and psychedelic use (e.g., greater self-understanding, less hierarchical attitudes toward colleagues, positive changes in interpersonal attitudes and behaviors), respectively. Conclusion: Although causality cannot be inferred due to the research design, the findings in this study suggest potential complementary effects of mindfulness meditation and psychedelic use on leadership, which could inspire new approaches in leadership development.

Misperceptions and Missed Opportunities: A Qualitative Analysis of Barriers to Evaluating Surgical Teachers.

OBJECTIVE: Teaching skills can be improved with written evaluations from learners. In addition to this primary purpose, teaching assessments are used in other aspects of faculty development including appointments, advancement and in some cases, compensation. Surgical trainees' willingness to provide meaningful assessments of their teachers is variable but the reasons for this are ill-defined. This study aims to elucidate surgical residents' perceptions regarding barriers to providing useful feedback to their teachers. DESIGN: A qualitative, semi-structured confidential interview approach was used. A demographically diverse cohort of surgical residents in an urban university-based program was invited to participate. Interviews explored experiences and perceptions of teaching assessments. Specific attention was paid to understand perceptions of barriers; topics including utility, anonymity, time burden, and others were explored. Interviews were transcribed verbatim with identifiers removed from transcripts before analysis. All data was double coded to ensure accuracy with the development of a codebook until thematic exhaustion was reached. SETTING: Yale New Haven Hospital is an academic, university-based medical center with approximately 70 residents in the general surgery program and approximately 170 surgical faculty. PARTICIPANTS: A total of 21 residents completed individual or small group interviews. A theoretically driven sampling technique was used to recruit participants and maximize diversity. Individuals with varying backgrounds including PGY year, gender, age, IMG status, race, academic rank, research background and surgical division were asked to participate. RESULTS: A total of 21 residents completed individual or small group interviews. Coding and analysis revealed 4 principal motifs: (1). Process- The process to complete assessment instruments is time-consuming and cumbersome to complete during the busy and acute surgical workday while failing to accurately address important aspects of surgical teaching. (2). Utility- Respondents reported uncertainty as to the downstream utility of the assessments, and a lack of confidence that the assessments would be used for faculty growth and improvement. (3). Resident Standing- Respondents described a lack of training, knowledge, skills, and empowerment to assess their teachers. (4). Perceived Consequences- Residents noted concern for identification, future autonomy, and other potential negative career consequences due to small resident sample sizes, recognizable experiences with attendings, and perceived power dynamics. CONCLUSIONS: This study elucidates the perceptions of surgical trainees regarding barriers to providing feedback and assessments of their faculty. Although limited to a single-institution study, residents observed the current system does not allow for honest and accurate evaluations of surgical teachers. The extensive overlap between motifs highlights the need for a holistic approach to address these interconnected themes before teaching evaluations can be honest and productive. Importantly, it is also the first to identify residents' perceived lack of skill and sense of disempowerment to provide constructive faculty assessment. Due to the limited scope of the single-institution study, further verification and studies are needed to improve the quality of faculty feedback and assessment of surgical teachers.

Nutrition Education Package Focusing on Infant and Young Child Feeding in Tanzania.

OBJECTIVE: To evaluate the effectiveness of a nutrition education package on feeding practices, nutrient intakes and growth of infants in rural Tanzania. DESIGN: Cluster-randomized controlled trial in 18 villages allocated to nutrition education package (n = 9) or routine health education (n = 9 villages), measured at baseline (6 months) and end of the trial (12 months). SETTING: Mpwapwa district. PARTICIPANTS: Infants aged 6-12 months and their mothers. INTERVENTION(S): Six months of nutrition education package (group education, counseling, cooking demonstrations) and regular home visits by village health workers. MAIN OUTCOME MEASURE(S): Primary outcome measure was the mean change in length-for-age z-scores. Secondary outcomes included mean changes in weight-for-length z-scores (WLZ), intakes of energy, fat, iron and zinc, the proportion of children consuming foods from ≥ 4 food groups (ie, dietary diversity) and consuming the recommended number of semisolid/soft meals and snacks per day (ie, meal frequency). ANALYSIS: Multilevel mixed-effects regression models. RESULTS: Mean change in length-for-age z-scores (ß = 0.20, P = 0.02), energy (in kcal) (ß = 43.8, P = 0.02), and fat (in grams) (ß =2.7, P = 0.03) intakes were significant in the intervention but not in the control group. There was no effect on iron and zinc intakes. More infants in the intervention than the control group consumed meals from ≥ 4 food groups (71.8% vs 45.3%, P = 0.002). The mean increase in meal frequency (ß = 0.29, P = 0.02) and dietary diversity (ß = 0.40, P = 0.01) were more significant in the intervention than control. CONCLUSIONS AND IMPLICATIONS: The nutrition education package is feasible and can be implemented with high coverage, demonstrating the potential to improve feeding practices, nutrient intake and growth in rural Tanzania.

A retrospective assessment of fuel break effectiveness for containing rangeland wildfires in the sagebrush biome.

Escalated wildfire activity within the western U.S. has widespread societal impacts and long-term consequences for the imperiled sagebrush (Artemisia spp.) biome. Shifts from historical fire regimes and the interplay between frequent disturbance and invasive annual grasses may initiate permanent state transitions as wildfire frequency outpaces sagebrush communities' innate capacity to recover. Therefore, wildfire management is at the core of conservation plans for sagebrush ecosystems, especially critical habitat for species of conservation concern such as the greater sage-grouse (Centrocercus urophasianus; hereafter sage-grouse). Fuel breaks help facilitate wildfire suppression by modifying behavior through fuels modification and allowing safe access points for containment by firefighters. The Bureau of Land Management has proposed to roughly double the existing fuel break network in the western U.S., centered on the Great Basin. To our knowledge, no broad-scale examination of fuel break effectiveness or the environmental conditions under which fuel breaks are expected to be most effective has been conducted. We performed a retrospective assessment of probability of fuel break contributing to wildfire containment on recorded wildfire and fuel break interactions from 1985 to 2018 within the western U.S. We characterized environmental, fuels, and weather conditions within 500 m of wildfire contact, and within 5 km of the approaching wildfire. We used a binomial mixed model within a Bayesian framework to identify relationships between these variables and fuel break success. Fuel breaks were least successful in areas classified as having low resilience to disturbance and low resistance to invasion, in areas composed of primarily woody fuels, and when operating in high temperature and low precipitation conditions. Fuel breaks were most effective in areas where fine fuels dominated and in areas that were readily accessible. Maintenance history and fuel break type also contributed to the probability of containment. Overall results indicate a complex and sometimes paradoxical relationship between landscape characteristics that promote wildfire spread and those that impact fuel break effectiveness. Finally, we developed predictive maps of fuel break effectiveness by fuel break type to further elucidate these complex relationships and to inform urgently needed fuel break placement and maintenance priorities across the sagebrush biome.

SLC26A1 is a major determinant of sulfate homeostasis in humans.

Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge. Whole-exome data analysis of more than 5,000 individuals confirmed that rare, putatively damaging SCL26A1 variants were significantly associated with lower plasma sulfate at the population level. Functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, which we consider to be novel, as well as for the additional variants detected in the population study. In conclusion, combined evidence from 3 complementary approaches supports SLC26A1 activity as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis with back pain and intervertebral disc disorder, our study identifies SLC26A1 as a potential target for modulation of musculoskeletal health.