A randomized controlled trial of a self-guided mobile app targeting repetitive negative thought to prevent depression in university students: study protocol of the Nurture-U Reducing Worry prevention trial.

BACKGROUND: Tackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students. METHODS: An online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored. DISCUSSION: The trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022.

Granulomatosis with Polyangiitis: A Rare but Clinically Important Disease for the Otolaryngologist.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is rare but debilitating autoimmune disease and commonly presents with sinonasal as well as other head and neck symptoms. AIMS: To summarize the ear, nose, and throat-specific symptomatology and management of GPA. METHODS AND RESULTS: We performed a literature review by using the PubMed search engine to provide a summary of recent and important literature that is pertinent to an otolaryngologist's clinical practice. We provide a guide on the pathophysiology, epidemiology, clinical features, investigation, and management (operative and nonoperative) of this important disease. CONCLUSIONS: This review illustrates the important role that an otolaryngologist can play in the work up and symptom management of patients with GPA. Knowledge of the common presenting symptoms as well as more rare presentations of GPA is extremely important for otolaryngologists as prompt diagnosis and management is extremely important to avoid significant morbidity and mortality.

Ecological disturbance alters the adaptive benefits of social ties.

Extreme weather events radically alter ecosystems. When ecological damage persists, selective pressures on individuals can change, leading to phenotypic adjustments. For group-living animals, social relationships may be a mechanism enabling adaptation to ecosystem disturbance. Yet whether such events alter selection on sociality and whether group-living animals can, as a result, adaptively change their social relationships remain untested. We leveraged 10 years of data collected on rhesus macaques before and after a category 4 hurricane caused persistent deforestation, exacerbating monkeys' exposure to intense heat. In response, macaques demonstrated persistently increased tolerance and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival after the hurricane, but not before it, revealing a shift in the adaptive function of sociality.

Natural disaster alters the adaptive benefits of sociality in a primate.

Weather-related disasters can radically alter ecosystems. When disaster-driven ecological damage persists, the selective pressures exerted on individuals can change, eventually leading to phenotypic adjustments. For group-living animals, social relationships are believed to help individuals cope with environmental challenges and may be a critical mechanism enabling adaptation to ecosystems degraded by disasters. Yet, whether natural disasters alter selective pressures on patterns of social interactions and whether group-living animals can, as a result, adaptively change their social relationships remains untested. Here, we leveraged unique data collected on rhesus macaques from 5 years before to 5 years after a category 4 hurricane, leading to persistent deforestation which exacerbated monkeys' exposure to intense heat. In response, macaques increased tolerance for and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival for 5 years after the hurricane, but not before it, revealing a clear shift in the adaptive function of social relationships in this population. We demonstrate that an extreme climatic event altered selection on sociality and triggered substantial and persistent changes in the social structure of a primate species. Our findings unveil the function and adaptive flexibility of social relationships in degraded ecosystems and identify natural disasters as potential evolutionary drivers of sociality. One-Sentence Summary: Testard et al. show that a natural disaster altered selection on sociality in group-living primates triggering persistent changes in their social structure.

The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes.

In autoimmune Type 1 diabetes (T1D), immune cells progressively infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, it is unclear how this process, called 'insulitis', develops and progresses within this organ. Here, using highly multiplexed CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples from pre-T1D, T1D, and non-T1D donors, we examine pseudotemporal-spatial patterns of insulitis and exocrine inflammation within large pancreatic tissue sections. We identify four sub-states of insulitis characterized by CD8 + T cells at different stages of activation. We further find that exocrine compartments of pancreatic lobules affected by insulitis have distinct cellularity, suggesting that extra-islet factors may make particular lobules permissive to disease. Finally, we identify "staging areas" - immature tertiary lymphoid structures away from islets where CD8 + T cells appear to assemble before they navigate to islets. Together, these data implicate the extra-islet pancreas in autoimmune insulitis, greatly expanding the boundaries of T1D pathogenesis.

Hepatopathy in Victorian dogs consuming pet meat contaminated with indospicine.

BACKGROUND: Indospicine is an arginine analogue and a natural toxin occurring only in Indigofera plant species, including Australian native species. It accumulates in the tissues of grazing animals, persisting for several months after ingestion. Dogs are particularly sensitive to indospicine toxicity and can suffer fatal liver disease after eating indospicine-contaminated pet meat. METHOD: A disease outbreak investigation was launched following notification to Agriculture Victoria of a cluster of 18 dogs displaying acute, severe, hepatopathy in the East Gippsland Shire in June 2021. RESULTS: Between June and September 2021, 24 pet dogs died, and 40 others experienced liver disease after eating commercially prepared pet meat found to contain indospicine. The investigation identified the toxin in serum and liver samples from affected dogs and at high levels in some samples of pet meat eaten by the dogs. Twenty-six horses that were moved from the Northern Territory and processed at a Pet Meat Processing facility (knackery) in eastern Victoria over a period of 14 days in late May-early June 2021 were identified as the likely source of the indospicine toxin in the pet meat. Pet meat produced by the knackery and on-sold by several retailers was determined to be the cause of the illness and death in the dogs. CONCLUSION: This is the first report of severe and frequently fatal hepatopathy in dogs in Victoria relating to consumption of pet meat contaminated with indospicine.

Localized Darier disease: three cases of Type 1 segmental mosaicism.

Darier disease (DD) is an autosomal dominant acantholytic dermatosis with an estimated prevalence of 1 in 30 000-100 000. A localized form of DD was first described by Kreibich in 1906 and is thought to account for 10% of all cases. A number of clinical variants have been reported including: unilateral, linear, segmental or zosteriform DD. We present a case series of three patients with localized DD.

A neglected source of household air pollution: a preliminary, mixed methods study of purposely produced household smoke in Wollo, Ethiopia.

BACKGROUND: Ill health associated with household air pollution (HAP) is increasingly recognized as a public health problem in sub-Saharan Africa. To date, attempts to reduce HAP have focussed on smoke from cooking fires and have ignored traditional cultural practices which generate purposely produced smoke (PPS). This study aimed to investigate PPS prevalence, reasons for use and safety perceptions. METHODS: The study was conducted in Wollo, Ethiopia, and used a mixed methods approach of quantitative surveys (analysed descriptively) and qualitative interviews with householders and healthcare workers (analysed thematically). RESULTS: PPS use was reported by 99% of survey respondents and it was considered a fundamental part of life. Although reasons for use included housekeeping, culture/religion and well-being, coffee ceremony was most commonly cited (44% of respondents). Both householders and healthcare workers appeared to assume PPS is safe, except for people with certain underlying conditions. Healthcare workers felt the lack of evidence of harm from PPS meant there was no justification for intervention. CONCLUSION: This study, the first in-depth study of PPS, has shown its use to be widespread, with many perceived benefits and thus a very important part of local culture in this sample Ethiopian community. Consequently, any public health interventions aimed at reducing HAP in this setting need to consider PPS.

How Well Do We Know the Neutron-Matter Equation of State at the Densities Inside Neutron Stars? A Bayesian Approach with Correlated Uncertainties.

We introduce a new framework for quantifying correlated uncertainties of the infinite-matter equation of state derived from chiral effective field theory (χEFT). Bayesian machine learning via Gaussian processes with physics-based hyperparameters allows us to efficiently quantify and propagate theoretical uncertainties of the equation of state, such as χEFT truncation errors, to derived quantities. We apply this framework to state-of-the-art many-body perturbation theory calculations with nucleon-nucleon and three-nucleon interactions up to fourth order in the χEFT expansion. This produces the first statistically robust uncertainty estimates for key quantities of neutron stars. We give results up to twice nuclear saturation density for the energy per particle, pressure, and speed of sound of neutron matter, as well as for the nuclear symmetry energy and its derivative. At nuclear saturation density, the predicted symmetry energy and its slope are consistent with experimental constraints.

Effects of Housing System on Dairy Heifer Replacement Cost From Birth to Calving: Evaluating Costs of Confinement, Dry-Lot, and Pasture-Based Systems and Their Impact on Total Rearing Investment.

Replacement heifer rearing is critical for the future of dairy operations, to improve genetic merit and maintain herd size. A myriad of options exist on how to manage, feed, and ultimately raise replacement heifers. Pasture is perceived to offer optimal welfare and an economical housing system for replacement animals, but confinement systems are gaining popularity. This study investigates the costs associated with replacement heifer management decisions from birth to calving, considering the factors of housing systems, labor, feed, and health. The objective of this study was to develop an economic model to determine the cost of raising a replacement heifer managed in confinement, dry-lot, and pasture-based scenarios post-weaning. We accounted for variation in feed, labor, and health inputs and quantified the impact of these individual management decisions. An economic simulation with 10,000 iterations were completed for each situation using @Risk and PrecisionTree add-ons (Palisade Corporation, Ithaca, NY) where health incidence, commodity prices, and management variables were made stochastic. Published literature or sample farm data created parameters used in Pert distributions. Costs and biological responses were reflective of published surveys, literature, and market conditions. Management decision inputs had 3 main factors: housing type, ration composition, and labor utilization. Housing systems were calculated separately for confinement, dry-lot, and pasture scenarios. The mean total cost (min, max) to raise a replacement heifer from birth to calving, assuming the same pre-weaning strategy of group housing with an automatic calf feeder, was found to be $1,919.02 ($1,777.25, $2,100.57), $1,593.57 ($1,490.30, $1,737.26), and $1,335.84 ($1,266.69, $1,423.94) for confinement, dry-lot, and pasture, respectively. Total housing cost per replacement heifer was $423.05, $117.96, and $207.96 for confinement, dry-lot, and pasture management systems, respectively. When compared to total cost, housing contributed 21% for confinement, 7% for dry-lot, and 15% for pasture. Upon analysis of all scenarios, utilizing pasture to raise heifers resulted in a lower overall cost when compared to confinement housing options. Percentage breakdowns of feed, labor, housing, and fixed and variable costs provided more information on efficiency rather than total cost, which makes each situation different in relation to on-farm cost. This cost analysis is critical to assisting farms in making decisions in the utilization of their resources for replacement dairy heifers.

Variability of TSNA in U.S. Tobacco and Moist Smokeless Tobacco Products.

Tobacco-specific nitrosamines (TSNAs) have been of concern to the public health community for decades and their reduction through agricultural practices, plant breeding, and tobacco processing has also been a decades-long industry effort. Despite those efforts, TSNAs, though lower, continue to be constituents of concern in tobacco products. This paper examines the TSNA levels of dark air-cured, dark fire-cured, and burley tobaccos purchased in the United States by U.S. Smokeless Tobacco Company LLC (USSTC) and of nine finished USSTC moist smokeless tobacco products. TSNA values of the incoming purchased tobaccos and the finished products showed considerable variability. For the incoming tobaccos, the coefficient of variation was generally more than 100 % for each tobacco type and for each of the measured TSNAs. The relative TSNA variability of the finished tobacco products was also considerable, averaging approximately 25 %. It was also found that the measured values for the finished products averaged well above the proposed FDA NNN proposed product standard of 1.0 µg/g dry weight. Because of the large variability in NNN values, products would have to average well below FDA's proposed product standard to be consistently compliant.

Detector-Agnostic Phase-Space Distributions.

The representation of quantum states via phase-space functions constitutes an intuitive technique to characterize light. However, the reconstruction of such distributions is challenging as it demands specific types of detectors and detailed models thereof to account for their particular properties and imperfections. To overcome these obstacles, we derive and implement a measurement scheme that enables a reconstruction of phase-space distributions for arbitrary states whose functionality does not depend on the knowledge of the detectors, thus defining the notion of detector-agnostic phase-space distributions. Our theory presents a generalization of well-known phase-space quasiprobability distributions, such as the Wigner function. We implement our measurement protocol, using state-of-the-art transition-edge sensors without performing a detector characterization. Based on our approach, we reveal the characteristic features of heralded single- and two-photon states in phase space and certify their nonclassicality with high statistical significance.

Short-term safety and effectiveness of sugammadex for surgical patients with end-stage renal disease: a two-centre retrospective study.

Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.

Quantum-enhanced interferometry with large heralded photon-number states.

Quantum phenomena such as entanglement can improve fundamental limits on the sensitivity of a measurement probe. In optical interferometry, a probe consisting of N entangled photons provides up to a N enhancement in phase sensitivity compared to a classical probe of the same energy. Here, we employ high-gain parametric down-conversion sources and photon-number-resolving detectors to perform interferometry with heralded quantum probes of sizes up to N = 8 (i.e. measuring up to 16-photon coincidences). Our probes are created by injecting heralded photon-number states into an interferometer, and in principle provide quantum-enhanced phase sensitivity even in the presence of significant optical loss. Our work paves the way towards quantum-enhanced interferometry using large entangled photonic states.

Non-communicable disease clinics in rural Ethiopia: why patients are lost to follow-up.

BACKGROUND: Providing medical care for non-communicable diseases (NCDs) in rural sub-Saharan Africa has proved to be difficult because of poor treatment adherence and frequent loss to follow-up (LTFU). The reasons for this are poorly understood. OBJECTIVE: To investigate LTFU among patients with two different but common NCDs who attended rural Ethiopian health centres. METHOD: The study was based in five health centres in southern Ethiopia with established NCD clinics run by nurses and health officers. Patients with epilepsy or hypertension who were lost to follow-up and non-LTFU comparison patients were identified and traced; a questionnaire was administered enquiring about the reasons for LTFU. RESULTS: Of the 147 LTFU patients successfully located, 62 had died, moved away or were attending other medical facilities. The remaining 85 patients were compared with 211 non-LFTU patients. The major factors associated with LTFU were distance from the clinic, associated costs and a preference for traditional treatments, together with a misunderstanding of the nature of NCD management. CONCLUSIONS: The delivery of affordable care closer to the patients' homes has the greatest potential to address the problem of LTFU. Also needed are increased levels of patient education and interaction with traditional healers to explain the nature of NCDs and the need for life-long management.

Modeling Epidemics in Seed Systems and Landscapes To Guide Management Strategies: The Case of Sweet Potato in Northern Uganda.

Seed systems are critical for deployment of improved varieties but also can serve as major conduits for the spread of seedborne pathogens. As in many other epidemic systems, epidemic risk in seed systems often depends on the structure of networks of trade, social interactions, and landscape connectivity. In a case study, we evaluated the structure of an informal sweet potato seed system in the Gulu region of northern Uganda for its vulnerability to the spread of emerging epidemics and its utility for disseminating improved varieties. Seed transaction data were collected by surveying vine sellers weekly during the 2014 growing season. We combined data from these observed seed transactions with estimated dispersal risk based on village-to-village proximity to create a multilayer network or "supranetwork." Both the inverse power law function and negative exponential function, common models for dispersal kernels, were evaluated in a sensitivity analysis/uncertainty quantification across a range of parameters chosen to represent spread based on proximity in the landscape. In a set of simulation experiments, we modeled the introduction of a novel pathogen and evaluated the influence of spread parameters on the selection of villages for surveillance and management. We found that the starting position in the network was critical for epidemic progress and final epidemic outcomes, largely driven by node out-degree. The efficacy of node centrality measures was evaluated for utility in identifying villages in the network to manage and limit disease spread. Node degree often performed as well as other, more complicated centrality measures for the networks where village-to-village spread was modeled by the inverse power law, whereas betweenness centrality was often more effective for negative exponential dispersal. This analysis framework can be applied to provide recommendations for a wide variety of seed systems.[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Major element data, 40Ar/39Ar step-heating and step-crushing data for anorthoclase megacrysts from the Newer Volcanic Province, south-eastern Australia.

We provide the dataset associated with the research article "40Ar/39Ar ages of alkali feldspar xenocrysts constrain the timing of intraplate basaltic volcanism" Matchan et al. [1]. This dataset contains major element data for 15 large anorthoclase xenocrysts ('megacrysts') collected from six Pleistocene eruption centres (Mount Leura, Mount Shadwell, Mount Noorat, Mount Franklin, Lake Keilambete and The Anakies (East Cone)) in the basaltic Newer Volcanic Province of south-eastern Australia. It also contains multi-collector (Argus VI) 40Ar/39Ar step-heating for 13 of these anorthoclase megacrysts. 40Ar/39Ar vacuo step-crushing experiment data is also provided for three of these megacrysts.

The influence of socioeconomic status on presentation and outcome of acute kidney injury.

AIM: Although socioeconomic background is known to impact on the incidence and progression of chronic kidney disease, its influence of on the presentation and outcome for acute kidney injury is not known and is the subject of this study. DESIGN: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients >18 years of age between March 2015 and November 2017. METHODS: Socioeconomic classification of patients was derived from the Welsh Index Multiple Deprivation score (WIMD). Patients were grouped according to the WIMD score by their postcode, and the ranked data were categorized into percentiles and correlated with incidence and measures of AKI severity and outcome. RESULTS: Date was collected on a total of 57 654 patients. Increased deprivation was associated with higher AKI incidence rates, more episodes of AKI per patient and more severe AKI at presentation. In contrast 90-day mortality was highest in the most affluent areas. Mortality in affluent areas was driven by increased patient age. Corrected for age 90-day mortality was higher in areas of increased deprivation. CONCLUSION: This study highlights that AKI incidence presentation and outcomes are adversely affected by social deprivation. Further studies are required to understand the extent to which these differences reflect patient related factors or regional differences in provision and access to care.

Bacterial Community Shift and Coexisting/Coexcluding Patterns Revealed by Network Analysis in a Uranium-Contaminated Site after Bioreduction Followed by Reoxidation.

A site in Oak Ridge, TN, USA, has sediments that contain >3% iron oxides and is contaminated with uranium (U). The U(VI) was bioreduced to U(IV) and immobilized in situ through intermittent injections of ethanol. It then was allowed to reoxidize via the invasion of low-pH (3.6 to 4.0), high-nitrate (up to 200 mM) groundwater back into the reduced zone for 1,383 days. To examine the biogeochemical response, high-throughput sequencing and network analysis were applied to characterize bacterial population shifts, as well as cooccurrence and coexclusion patterns among microbial communities. A paired t test indicated no significant changes of α-diversity for the bioactive wells. However, both nonmetric multidimensional scaling and analysis of similarity confirmed a significant distinction in the overall composition of the bacterial communities between the bioreduced and the reoxidized sediments. The top 20 major genera accounted for >70% of the cumulative contribution to the dissimilarity in the bacterial communities before and after the groundwater invasion. Castellaniella had the largest dissimilarity contribution (17.7%). For the bioactive wells, the abundance of the U(VI)-reducing genera Geothrix, Desulfovibrio, Ferribacterium, and Geobacter decreased significantly, whereas the denitrifying Acidovorax abundance increased significantly after groundwater invasion. Additionally, seven genera, i.e., Castellaniella, Ignavibacterium, Simplicispira, Rhizomicrobium, Acidobacteria Gp1, Acidobacteria Gp14, and Acidobacteria Gp23, were significant indicators of bioactive wells in the reoxidation stage. Canonical correspondence analysis indicated that nitrate, manganese, and pH affected mostly the U(VI)-reducing genera and indicator genera. Cooccurrence patterns among microbial taxa suggested the presence of taxa sharing similar ecological niches or mutualism/commensalism/synergism interactions.IMPORTANCE High-throughput sequencing technology in combination with a network analysis approach were used to investigate the stabilization of uranium and the corresponding dynamics of bacterial communities under field conditions with regard to the heterogeneity and complexity of the subsurface over the long term. The study also examined diversity and microbial community composition shift, the common genera, and indicator genera before and after long-term contaminated-groundwater invasion and the relationship between the target functional community structure and environmental factors. Additionally, deciphering cooccurrence and coexclusion patterns among microbial taxa and environmental parameters could help predict potential biotic interactions (cooperation/competition), shared physiologies, or habitat affinities, thus, improving our understanding of ecological niches occupied by certain specific species. These findings offer new insights into compositions of and associations among bacterial communities and serve as a foundation for future bioreduction implementation and monitoring efforts applied to uranium-contaminated sites.