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IntroductionMultimorbidity, the coexistence of two or more chronic conditions, has been extensively studied in certain disease states. Bronchiectasis aetiology is complex and multimorbidity is insufficiently understood. We performed a scoping review, summarising the existing literature and identifying deficits.MethodA literature search of the electronic databases PubMed, CINAHL and EMBASE was conducted following PRISMA guidelines. Observational, interventional, qualitative, randomised control trials and systematic reviews were included. The main objective was to identify prevalence, prognosis, symptoms, quality of life and management in bronchiectasis multimorbidity. Key findings were analysed descriptively.Results40 studies (200 567 patients) met the inclusion criteria, the majority (68%) being cohort studies. Study size ranged from 25 to 57 576 patients, with mean age 30–69 years. 70% of studies investigated the prognosis of comorbidities and 68% prevalence; 70% analysed multiple comorbidities in bronchiectasis. The most frequent comorbid diseases evaluated were COPD (58%), cardiovascular disease (53%) and asthma (40%). COPD and hypertension were the most prevalent conditions (pooled mean 35% and 34% respectively). Multimorbidity was associated with increased mortality, exacerbations and hospitalisation rates. It had a negative impact on lung function. Mortality increased in the following comorbidities: COPD, gastro-oesophageal reflux disease and rheumatoid arthritis.ConclusionBronchiectasis multimorbidity is common. Research focuses on a few key aspects and favoured comorbidities (e.g.COPD). There is a deficit of research into symptoms, quality of life, interactions and management. High-resolution computed tomography diagnosis is not consistent, and there is no agreed multimorbidity screening questionnaire. Bronchiectasis multimorbidity is of importance; it is associated with morbidity and mortality.

Strangers routinely cooperate and exchange goods without any knowledge of one another in one-off encounters without recourse to a third party, an interaction that is fundamental to most human societies. However, this act of reciprocal exchange entails the risk of the other agent defecting with both goods. We examine the choreography for safe exchange between strangers, and identify the minimum requirement, which is a shared hold, either of an object, or the other party; we show that competing agents will settle on exchange as a local optimum in the space of payoffs. Truly safe exchanges are rarely seen in practice, even though unsafe exchange could mean that risk-averse agents might avoid such interactions. We show that an ‘implicit’ hold, whereby an actor believes that they could establish a hold if the other agent looked to be defecting, is sufficient to enable the simple swaps that are the hallmark of human interactions and presumably provide an acceptable trade-off between risk and convenience. We explicitly consider the particular case of purchasing, where money is one of the goods.

Glioblastoma (GBM) is a devastating brain cancer with no effective treatment, and there is an urgent need for developing innovative biomarkers as well as therapeutic targets for better management of the disease. The membrane protein sortilin has recently been shown to participate in tumor cell invasiveness in several cancers, but its involvement and clinical relevance in GBM is unclear. In the present study, we explored the expression of sortilin and its potential as a clinical biomarker and therapeutic target for GBM. Sortilin expression was investigated by immunohistochemistry and digital quantification in a series of 71 clinical cases of invasive GBM vs. 20 non-invasive gliomas. Sortilin was overexpressed in GBM and, importantly, higher expression levels were associated with worse patient survival, pointing to sortilin tissue expression as a potential prognostic biomarker for GBM. Sortilin was also detectable in the plasma of GBM patients by enzyme-linked immunosorbent assay (ELISA), but no differences were observed between sortilin levels in the blood of GBM vs. glioma patients. In vitro, sortilin was detected in 11 brain-cancer-patient-derived cell lines at the anticipated molecular weight of 100 kDa. Interestingly, targeting sortilin with the orally bioavailable small molecule inhibitor AF38469 resulted in decreased GBM invasiveness, but cancer cell proliferation was not affected, showing that sortilin is targetable in GBM. Together, these data suggest the clinical relevance for sortilin in GBM and support further investigation of GBM as a clinical biomarker and therapeutic target.

Random telegraph noise (RTN) adversely induces time dependent device-to-device variations and requires modeling to optimize circuit design. Many early works were focused under dc test conditions, although digital circuits typically operate under ac conditions and it has been reported that ac RTN is substantially different from dc RTN. Tests on ac RTN were carried out mainly on individual traps, and a reliable statistical distribution of trap time constants for ac RTN is still missing. This prevents verifying the statistical accuracy of Monte Carlo ac RTN simulation based on compact models, especially in terms of their ability to predict ac RTN as time window increases. Recently, an integral methodology has been proposed for dc RTN, which can not only model it at short time but also predict it at long time. By introducing the concept of effective charged traps, the need for statistical distribution of trap time constants is removed, making RTN prediction similar to aging prediction. The objectives of this work are to report statistical experimental ac RTN data and to test the applicability of integral methodology to them. For the first time, it will be shown that a model extracted from a time window of 7.8 s can be used to predict the statistical distribution of long-term (3 × 10 4 s) ac RTN. The dependence of ac RTN on frequency and time window is analyzed, and the contributions of carrier tunneling from gate and substrate are assessed.

Loneliness is a potent psychosocial stressor that predicts poor health and mortality among older adults, possibly in part by accelerating age-related declines in immunocompetence. Mindfulness interventions have shown promise for reducing loneliness and improving markers of physical health. In a sample of lonely older adults, this two-arm parallel trial tested whether mindfulness training enhances stimulated interleukin-6 (IL-6) production, a measure of innate immune responsivity. Lonely older adults (65-85 years; N = 190) were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR) or control Health Enhancement Program (HEP) intervention. Lipopolysaccharide (LPS)-stimulated production of IL-6 was measured in vitro by blinded outcome assessors at pre-intervention, post-intervention, and 3-month follow-up. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR vs. HEP) effects. As predicted, a significant time × condition effect on stimulated IL-6 production was observed across pre, post, and follow-up timepoints. Significant MBSR vs. HEP differences emerged from pre- to post-intervention (p =.009, d = 0.38) and from pre-intervention to 3-month follow-up (p =.017, d = 0.35), with larger increases in IL-6 production following MBSR compared to HEP. No study-related adverse events were reported. Results show that mindfulness training may be effective for boosting innate immunocompetence among lonely older adults. Given that immunocompetence tends to decline with age, mindfulness training may help to counteract the effects of aging and psychosocial stress on infection risk and recovery from injury.

Introduction: the COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: to understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and methods: our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: the COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: the COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation., Novartis; Sanofi; Menarini Universidad Espiritu Santo; Takeda; Allakos; AstraZeneca; CSL Behring; Genentech; Pharming; GSK; Shire/Takada; BioCryst; ResTORbio; Pearl Therapeutics, CVS Health; Law offices of Levin; Riback; Adelman; Flangel; Vedder Price; Fresenius; Taiho; Kyowa Kirin; Tanabe; Korin; Uriach Pharma; Instituto Carlos III FEDER; Menarini; Amgen; Thermo Fisher; Avene; ALK‐Abello; Bencard/Allergy Therapeutics; Celgene; Allergopharma; Faes Farma; AbbVie; Janssen; Leo Pharma; Lilly; Roche; Genesis; Menlo Therapeutics; UCB; Pfizer; Almirall; Galderma; Allergika; Beiersdorf; Biocryst; Biogen Idec; BMS; Boehringer‐Ingelheim; Eli‐Lilly; Galderma; Hexal; Klosterfrau; LEO‐Pharma; LETI‐Pharma; L´Oreal; Medice; Octapharma; Pflüger; Pharming; Regeneron; Shire; ALK‐Abello; Fraunhofer‐IZI Leipzig; Hautnetz Leipzig/Westsachsen; MSD; HAL‐Allergy; Bencard; Nestle; Nutricia; Bayer Health Care; FAES; Henkel; Allakos; Argenx; Genentech Menarini; Moxie; Aralez; Celldex

Glioblastoma multiforme (GBM) is the most lethal adult brain cancer. Temozolomide (TMZ), the standard chemotherapeutic drug used in GBM, has limited benefit and alternate therapies are needed to improve GBM treatment. Nerve growth factor (NGF) and its precursor proNGF are increasingly recognized as stimulators of human tumor progression. The expression and stimulatory effect of NGF on GBM cell growth has previously been reported, but the status of proNGF in GBM is unreported. In this study, we have investigated proNGF expression and biological activity in GBM. A clinical cohort of GBM (n = 72) and low-grade glioma (n = 20) was analyzed by immunohistochemistry for proNGF and digital quantification. ProNGF expression was significantly increased in GBM compared to low grade gliomas and proNGF was also detected in patient plasma samples. ProNGF was also detected in most GBM cell lines by Western blotting. Although anti-proNGF blocking antibodies inhibited cell growth in GBM cells with methylated MGMT gene promoter, targeting proNGF could not potentiate the efficacy of TMZ. In subcutaneous xenograft of human GBM cells, anti-proNGF antibodies slightly reduced tumor volume but had no impact on TMZ efficacy. In conclusion, this data reveals that proNGF is overexpressed in GBM and can stimulate cancer cell growth. The potential of proNGF as a clinical biomarker and therapeutic target warrants further investigations.

We analyse and document the historical simulations performed by two versions of the Australian Community Climate and Earth System Simulator (ACCESS-CM2 and ACCESS-ESM1.5) for the Coupled Model Intercomparison Project Phase 6 (CMIP6). Three ensemble members from each model are used to compare the simulated seasonal-mean climate, climate variability and climate change with observations over the historical period. Where appropriate, we also compare the ACCESS model results with the results from 36 other CMIP6 models. We find that the simulations of the winter and summer mean climates (over the global domain) by the two ACCESS models are similar to or better than most of the other CMIP6 models for surface temperature, precipitation and surface specific humidity. For sea-level pressure, both ACCESS models perform worse than most other models. The spatial structures of the prominent climate variability modes (ENSO, IOD, IPO and AMO) also compare favourably with the corresponding observed structures. However, the results for the simulation of the models’ temporal variability are mixed. In particular, whereas ACCESS-ESM1.5 simulates ENSO events with ~3-year periods (that are closer to the observed periods of 3–7 years), the ACCESS-CM2 simulates ENSO events having quasi-biennial periods. However, ACCESS-CM2 has a much smaller bias (−0.1 W m−2) in present-day top-of-the-atmosphere energy balance than ACCESS-ESM1.5 (−0.6 W m−2). The ACCESS models simulate the anthropogenic climate change signal in historical global-mean surface temperature reasonably well, although the simulated signal variances are ~10% weaker than the observed signal variance (a common bias in most CMIP6 models). Both models also well simulate the major features of observed surface temperature changes, as isolated using a multiple regression model. Despite some identified biases, the two ACCESS models provide high-quality climate simulations that may be used in further analyses of climate variability and change.

The Australian Community Climate and Earth System Simulator (ACCESS) has contributed to the World Climate Research Programme’s Coupled Model Intercomparison Project Phase 6 (CMIP6) using two fully coupled model versions (ACCESS-CM2 and ACCESS-ESM1.5) and two ocean–sea-ice model versions (1° and 0.25° resolution versions of ACCESS-OM2). The fully coupled models differ primarily in the configuration and version of their atmosphere components (including the aerosol scheme), with smaller differences in their sea-ice and land model versions. Additionally, ACCESS-ESM1.5 includes biogeochemistry in the land and ocean components and can be run with an interactive carbon cycle. CMIP6 comprises core experiments and associated thematic Model Intercomparison Projects (MIPs). This paper provides an overview of the CMIP6 submission, including the methods used for the preparation of input forcing datasets and the post-processing of model output, along with a comprehensive list of experiments performed, detailing their initialisation, duration, ensemble number and computational cost. A small selection of model output is presented, focusing on idealised experiments and their variants at global scale. Differences in the climate simulation of the two coupled models are highlighted. ACCESS-CM2 produces a larger equilibrium climate sensitivity (4.7°C) than ACCESS-ESM1.5 (3.9°C), likely a result of updated atmospheric parameterisation in recent versions of the atmospheric component of ACCESS-CM2. The idealised experiments run with ACCESS-ESM1.5 show that land and ocean carbon fluxes respond to both changing atmospheric CO2 and to changing temperature. ACCESS data submitted to CMIP6 are available from the Earth System Grid Federation (https://doi.org/10.22033/ESGF/CMIP6.2281 and https://doi.org/10.22033/ESGF/CMIP6.2288). The information provided in this paper should facilitate easier use of these significant datasets by the broader climate community.

Both low-grade elevation in peripheral inflammatory markers (e.g., white blood count (WBC) and C-reactive protein (CRP)) and physical illness (both chronic and acute) have been associated with depressive symptomology. However, it is unclear if low-grade elevation in inflammatory markers mediates relationships between physical illness and depression or if physical illness positively moderates relationships between inflammatory markers and depression.In a well-powered, racially diverse cohort (n = 21,525) from NHANES datasets, we examined if inflammatory markers (CRP and WBC) and physical illnesses (acute and chronic) were independently associated with depression severity. We also examined if associations between physical illness and depression severity were mediated by inflammatory markers and if physical illness moderated associations between inflammatory markers and depression.We found that both inflammatory markers and physical illness were associated with depression severity, even after considering a wide range of potential confounders (e.g., age, gender, body mass index). Inflammatory markers mediated a marginal portion (5%; p 0.001) of potential effects of physical illness on depression severity. In moderation analyses, associations between inflammatory markers and depression severity were significantly stronger in participants with chronic physical illness than those without. This moderating effect was not present for acute physical illness.Inflammatory markers and physical illness appear independently linked to depression severity and, in individuals with chronic physical illness, inflammatory markers are more tightly connected to depressive symptomology. Such findings could help guide future individualized treatment research for depression based on both inflammatory marker level and physical illness burden.

Random telegraph noise (RTN) adversely impacts circuit performance and this impact increases for smaller devices and lower operation voltage. To optimize the circuit design, many efforts have been made to model RTN. RTN is highly stochastic, with significant device-to-device variations (DDVs). Early works often characterize individual traps first and then group them together to extract their statistical distributions. This bottom-up approach suffers from limitations in the number of traps it is possible to measure, especially for the capture and emission time constants, calling the reliability of extracted distributions into question. Several compact models have been proposed, but their ability to predict long-term RTN is not verified. Many early works measured RTN only for tens of seconds, although a longer time window increases RTN by capturing slower traps. The aim of this work is to propose an integral methodology for modeling RTN and, for the first time, to verify its capability of predicting the long-term RTN. Instead of characterizing properties of individual traps/devices, the RTN of multiple devices was integrated to form one dataset for extracting their statistical properties. This allows using the concept of effective charged traps (ECTs) and transforms the need for time constant distribution to obtain the kinetics of ECT, making long-term RTN prediction similar to predicting aging. The proposed methodology opens the way for assessing RTN impact within a window of ten years by efficiently evaluating the probability of a device parameter at a given level.

Accurate diagnosis of coronavirus disease 2019 is essential to limiting transmission within healthcare settings. The aim of this study was to identify patient demographic and clinical characteristics that could impact the clinical sensitivity of the nasopharyngeal severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) reverse transcription polymerase chain reaction (RT-PCR) test.We conducted a retrospective, matched case-control study of patients who underwent repeated nasopharyngeal SARS-CoV2 RT-PCR testing at a tertiary care academic medical center between March 1 and July 23, 2020. The primary endpoint was conversion from negative to positive PCR status within 14 days. We conducted conditional logistic regression modeling to assess the associations between demographic and clinical features and conversion to test positivity.Of 51,116 patients with conclusive SARS-CoV2 nasopharyngeal RT-PCR results, 97 patients converted from negative to positive within 14 days. We matched those patients 1:2 to 194 controls by initial test date. In multivariate analysis, clinical suspicion for a respiratory infection (adjusted odds ratio [aOR] 20.9, 95% confidence interval [CI]: 3.1-141.2) and lack of pulmonary imaging (aOR 4.7, 95% CI: 1.03-21.8) were associated with conversion, while a lower burden of comorbidities trended toward an increased odds of conversion (aOR 2.2, 95% CI: 0.9-5.3).Symptoms consistent with a respiratory infection, especially in relatively healthy individuals, should raise concerns about a clinical false-negative result. We have identified several characteristics that should be considered when creating institutional infection prevention guidelines in the absence of more definitive data and should be included in future studies.

Patients with oxidative phosphorylation (OxPhos) defects causing mitochondrial diseases appear particularly vulnerable to infections. Although OxPhos defects modulate cytokine production in vitro and in animal models, little is known about how circulating leukocytes of patients with inherited mitochondrial DNA (mtDNA) defects respond to acute immune challenges. In a small cohort of healthy controls (n=21) and patients (n=12) with either the m.3243A>G mutation or single, large-scale mtDNA deletions, we examined: i) cytokine responses (IL-6, TNF-α, IL-1β) in response to acute lipopolysaccharide (LPS) exposure, and ii) sensitivity to the immunosuppressive effects of glucocorticoid signaling (dexamethasone) on cytokine production. In dose-response experiments to determine the half-maximal effective LPS concentration (EC50), relative to controls, leukocytes from patients with mtDNA deletions showed 74 - 79% lower responses for IL-6 and IL-1β (pIL-6=0.031, pIL-1β=0.009). Moreover, IL-6 response to LPS in presence of GC was also blunted in cells from patients with mtDNA deletions (pIL-6=0.006), but not in leukocytes from patients with the m.3243A>G mutation. Overall, these ex vivo data provide preliminary evidence that some systemic OxPhos defects may compromise immune cytokine responses and glucocorticoid sensitivity. Further work in larger cohorts is needed to define the nature of immune dysregulation in patients with mitochondrial disease, and their potential implications for disease phenotypes.

A de Rham p-current can be viewed as a map (the current map) between the set of embeddings of a closed p-dimensional manifold into an ambient n-manifold and the set of linear functionals on differential p-forms. We demonstrate that, for suitably chosen Sobolev topologies on both the space of embeddings and the space of p-forms, the current map is continuously differentiable, with an image that consists of bounded linear functionals on p-forms. Using the Riesz representation theorem, we prove that each p-current can be represented by a unique co-exact differential form that has a particular interpretation depending on p. Embeddings of a manifold can be thought of as shapes with a prescribed topology. Our analysis of the current map provides us with representations of shapes that can be used for the measurement and statistical analysis of collections of shapes. We consider two special cases of our general analysis and prove that: (1) if $$p=n-1$$ p = n - 1 then closed, embedded, co-dimension one surfaces are naturally represented by probability distributions on the ambient manifold and (2) if $$p=1$$ p = 1 then closed, embedded, one-dimensional curves are naturally represented by fluid flows on the ambient manifold. In each case, we outline some statistical applications using an $${\dot{H}}^{1}$$ H ˙ 1 and $$L^{2}$$ L 2 metric, respectively.

Obsessive-compulsive disorder (OCD) affects 2–3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal–ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

BACKGROUND AND OBJECTIVES Representative enrollment of racial and ethnic minoritized populations in biomedical research ensures the generalizability of results and equitable access to novel therapies. Previous studies on pediatric clinical trial diversity are limited to subsets of journals or disciplines. We aimed to evaluate race and ethnicity reporting and representation in all US pediatric clinical trials on ClinicalTrials.gov. METHODS We performed a cross-sectional study of US-based clinical trials registered on ClinicalTrials.gov that enrolled participants aged RESULTS Among 1183 trials encompassing 405 376 participants, race and ethnicity reporting significantly increased from 27% in 2007 to 87% in 2018 (P < .001). The median proportional enrollment of Asian American children was 0.6% (interquartile range [IQR], 0%–3.7%); American Indian, 0% (IQR, 0%–0%); Black, 12% (IQR, 2.9%–28.4%); Hispanic, 7.1% (IQR, 0%–18.6%); and white 66.4% (IQR, 41.5%–81.6%). Asian American, Black, and Hispanic participants were underrepresented relative to US population demographics. Compared with expected proportions based on disease prevalence and hospitalizations, Asian American and Hispanic participants were most consistently underrepresented across diagnoses. CONCLUSIONS While race and ethnicity reporting in pediatric clinical trials has improved, the representative enrollment of minoritized participants remains an ongoing challenge. Evidence-based and policy solutions are needed to address these disparities to advance biomedical innovation for all children.

Ecosystems are commonly organized into trophic levels -- organisms that occupy the same level in a food chain (e.g., plants, herbivores, carnivores). A fundamental question in theoretical ecology is how the interplay between trophic structure, diversity, and competition shapes the properties of ecosystems. To address this problem, we analyze a generalized Consumer Resource Model with three trophic levels using the zero-temperature cavity method and numerical simulations. We find that intra-trophic diversity gives rise to ``emergent competition'' between species within a trophic level due to feedbacks mediated by other trophic levels. This emergent competition gives rise to a crossover from a regime of top-down control (populations are limited by predators) to a regime of bottom-up control (populations are limited by primary producers) and is captured by a simple order parameter related to the ratio of surviving species in different trophic levels. We show that our theoretical results agree with empirical observations, suggesting that the theoretical approach outlined here can be used to understand complex ecosystems with multiple trophic levels., Main text: 10.5 pages, 7 figures (Total: 18 pages)

Meta-analyses indicate that positive psychological interventions are effective at increasing positive affect, as well as reducing anxiety and depression; however, it is unclear how well these effects generalize during periods of high stress. Therefore, the current study tested whether a 2-week online positive psychological intervention delivered during the COVID-19 pandemic, a naturalistic stressor, (1) increased positive affect; (2) improved psychological well-being, optimism, life satisfaction, perceived social support, and loneliness; (3) and reduced negative affect in college students, a group known to have high pandemic distress. Participants (N = 250; 76.9% female) ages 18-45 were recruited from the University of Pittsburgh undergraduate subject pool between September and November of 2020. Participants were randomized to the online positive psychological intervention or active control condition and stratified by trait positive affect, sex, and year in college. Participants in both conditions completed one writing activity every other day for two consecutive weeks. Control participants documented their activities for that day (e.g., meals, going to gym). Intervention participants chose from six positive psychology activities. All outcome variables were assessed pre- and post-intervention by validated questionnaires. Across both conditions, positive and negative affect decreased from pre- to post-intervention. No other psychological factor differed by condition, time, or their interaction. The current null findings are in line with a more recent meta-analysis indicating that positive psychological interventions may have smaller effects on psychological well-being and depressive symptoms than was reported pre-pandemic. Study findings may suggest reduced efficacy of virtual positive psychological interventions under highly stressful circumstances.Supplementary informationThe online version contains supplementary material available at 10.1007/s42761-022-00148-z.

Psychosocial factors are related to immune, viral, and vaccination outcomes. Yet, this knowledge has been poorly represented in public health initiatives during the COVID-19 pandemic. This review provides an overview of biopsychosocial links relevant to COVID-19 outcomes by describing seminal evidence about these associations known prepandemic as well as contemporary research conducted during the pandemic. This focuses on the negative impact of the pandemic on psychosocial health and how this in turn has likely consequences for critically relevant viral and vaccination outcomes. We end by looking forward, highlighting the potential of psychosocial interventions that could be leveraged to support all people in navigating a postpandemic world and how a biopsychosocial approach to health could be incorporated into public health responses to future pandemics.

Introduction There is a concomitant rise in suicide rates with the prevalence of opioids involved in overdose deaths, especially among adolescents and young adults. However, there are limited studies on whether opioid use prospectively predicts suicidal behavior in youth. Methods Our sample included 183 psychiatric patients (18-30 years) admitted for a suicide attempt (SA), have current suicidal ideation (SI), and psychiatric controls without ideation or attempt (PC). Suicidal behavior was assessed using the Columbia Suicide Severity Rating Scale. We also recruited a healthy control group (HC; n = 40). Patients and controls were followed over a year. ANOVA, regression, and cox regression were used. Results Suicide attempt (β = 0.87, CI [0.1-1.6], p = 0.02) and SI [(β = 0.75, CI [0.03-1.5], p = 0.04) were significantly more likely than HCs to have used opioids in the past year at baseline. Opioid use was associated with increased anxiety symptoms (β = 0.75, CI [0.001-1.5], p = 0.05), PTSD symptoms (β = 3.90, CI [1.1-6.7], p = 0.01), and aggression (β = 0.02, CI [0.01-0.04], p = 0.02). Opioid use in the month prior to hospitalization predicted SA at 6 months (OR = 1.87, CI [1.06-3.31], p = 0.032). Conclusions Opioid use is a proximal predictor for SA. These findings may help clinicians better identify patients at risk for suicidal behavior, allowing for more personalized treatment approaches.

Introduction Chronic spontaneous (previously known as idiopathic) urticaria (CSU) is a chronic skin disease with the potential for natural remission. The objectives of this targeted literature review were to identify evidence on the clinical course of CSU, including remission rates, and to estimate cumulative remission rates for different time points. Methods Electronic databases (MEDLINE, MEDLINE-In Process, Embase, Web of Science, BIOSIS Previews and the Cochrane Library) and relevant conference proceedings were searched to identify studies involving patients with CSU aged ≥ 12 years that provide data on remission rates and disease duration. Observational studies with patient follow-ups of ≥ 1 year or review articles were included. Data extracted from five selected studies were used to run Kaplan–Meier (KM) analyses and best-fit distributions to calculate remission rates per 4-week period and weighted averages. Results Ten publications were included in this review. The proportion of patients achieving remission within year 1 ranged from 21 to 47%, while reported remission rate estimates at year 5 were 34% and 45%. Based on calculated 4-weekly remission rates, cumulative remission estimates ranged from 9 to 38% at year 1, from 29 to 71% at year 5 and from 52 to 93% at year 20. Cumulative weighted average estimates for the proportion of patients remitting at years 1, 5 and 20 were 17%, 45% and 73%, respectively. Conclusions Published evidence suggests that CSU is a self-limiting condition with variable disease severity and duration, apparently dependent on multiple factors. However, data sources differed in terms of definitions of disease severity and remission, as well as in conclusions on influencing factors. Further studies and uniform definitions are required. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00641-6.

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: Contrast-enhanced ultrasound (CEUS) has clear advantages over alternative imaging methods for the characterisation of renal abnormalities. It does not utilize ionizing radiation, is not nephrotoxic and has an established safety profile [1], making...

BACKGROUND AND AIMS: Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in the complex gut milieu in response to CF transmembrane conductance regulator (CFTR) dysfunction, pancreatic malabsorption, diet, medications, and environmental influences. In several diseases, alteration of the gut microbiota influences local and systemic inflammation and disease outcomes. We conducted a systematic review of the gut microbiota in CF and explored factors influencing dysbiosis. METHODS: An electronic search of three databases was conducted in January 2019, and re-run in June 2021. Human, animal, and in vitro studies were included. The primary outcome was differences in the gut microbiota between people with CF (pwCF) and healthy controls. Secondary outcomes included the relationship between the gut microbiota and other factors, including diet, medication, inflammation, and pulmonary function in pwCF. RESULTS: Thirty-eight studies were identified. The literature confirmed the presence of CF-related gut dysbiosis, characterized by reduced diversity and several taxonomic changes. There was a relative increase of bacteria associated with a pro-inflammatory response coupled with a reduction of those considered anti-inflammatory. However, studies linking gut dysbiosis to systemic and lung inflammation were limited. Causes of gut dysbiosis were multifactorial, and findings were variable. Data on the impact of CFTR modulators on the gut microbiota were limited. CONCLUSIONS: CF-related gut dysbiosis is evident in pwCF. Whether this influences local and systemic disease and is amenable to interventions with diet and drugs, such as CFTR modulators, requires further investigation.

The ocean/sea-ice interaction in the Southern Ocean is investigated using the Hamburg Ocean Primitive Equation Model (HOPE). The ocean model is three dimensional and prognostically calculates velocity, temperature, salinity and sea-surface elevation on a multi-level staggered Arakawa E-grid. Coupled to this is a thermodynamic model of sea-ice growth and melt, and a dynamic model with viscous-plastic rheology. Two versions have been formulated: a high-resolution re-entrant channel model of the East Antarctic coastline; and a medium-resolution southern hemisphere model. In the high-resolution model the mean annual oceanic heat flux (OHF) to the sea-ice (8 W m -2 ) is dominated by convection. There is considerable seasonal variability in the OHF, with areal-averaged values approaching 20 W m-2in winter, and falling below 5 W M-2 in summer. There is also considerable spatial variability in the OHF: near the sea-ice edge mean monthly values can be above 100 W m -2; within a coastal polynya, where the maximum annual in situ sea-ice growth is 15 m, values approach 50 W m-2; in the seasonal zone (62-64°S) an OHF in the range 5-20 W m -2 is common in the winter months; but for most of the year at most other locations the oceanic heat flux lies in the range of 0-5 W m-2 . Sensitivities to the magnitudes of sea-ice salinity and precipitation minus evaporation (P-E) are investigated. The model is found to be very sensitive to processes that affect the sea surface salinity, which determines the vertical stability of the ocean. In turn this controls the rate of convection, and consequently the sea-ice thickness. For the extreme case of zero P-E the model enters into a mode of temperature-driven deep convection, characterised by relatively warm sea surface temperature and a total collapse of the seasonal sea-ice cycle. The medium-resolution version is used to investigate the response of the coupled ocean/sea-ice system to a number of surface fresh water flux (SFWF) climatologies, and to changes in the mean surface air temperature in the southern hemisphere. As with the high-resolution model the seaice is very sensitive to the SFWF. In particular, the occurrence of a large scale polynya in the Weddell Sea is found to depend critically on there being a sufficient SFWF. The mean annual OHF for the Southern Ocean is found to be around 25 W m -2 , also with considerable seasonal and spatial variability. Increasing the SFWF by 10 cm a-1results in a decrease of 10% in the OHF, while increasing the surface air temperature by 2°C increases the OHF by 10%. The increase in surface air temperature results in a decrease in mean annual sea-ice extent and volume of around 20%, while the increase in SFWF results in an increase in mean annual sea-ice extent of around 5%, and an increase in mean annual sea-ice thickness of around 12%.

The global ocean plays a crucial role in modulating Earth’s present and future climate. In addition, most anthropogenic heat is stored in the ocean, causing thermal expansion of seawater, and consequently raising the global mean sea level. However, there is a large disagreement across climate models in the projection of ocean heat content (OHC) change and sea level rise. Here, we investigate climate model spread in OHC change in response to surface flux perturbations applied to climate models as part of the Flux-Anomaly-Forced Model Intercomparison Project (FAFMIP) simulations. The inter-model spread in OHC change, decomposed by physical processes, is large where the OHC change (i.e., signal) is large in response to individual surface flux forcing anomalies and mostly at similar locations as in the control simulations. OHC spread per basin is largest in the Atlantic Ocean response to perturbed surface heat flux, and Southern Ocean has largest spread in response to perturbed surface freshwater and momentum fluxes. This study shows that the largest inter-model spread in the vertical transport of heat is from resolved and mesoscale advective processes, and it is mostly seen in the eddy energetic and frontal regions both with and without perturbed forcings. The regional spread in OHC change and resolved advection is ~2 times larger than the internal variability in response to surface heat flux perturbation and within the range of unforced (~internal) variability response to surface freshwater and wind stress forcing at most places.&nbsp, The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

"March 2010".Project Number: Fish and Fish Habitats of the Pike River Anabranch and Floodplain Complex - MBUS|309.MDFRC item.Spatial segregation of species, due to differences in habitat use, is important for the health and structure of fish communities. River regulation in the Murray-Darling Basin has resulted in alerted flow regimes, restrictions to fish movement and decreases in available habitat for fish. In the South Australian River Murray, off-channel habitats such as Chowilla, Katarapko and the Pike Anabranch systems may provide important habitat for fish.The Pike Anabranch system consists of a series of creeks, backwaters and lagoons extending over 4,000 ha of floodplain, between the townships of Paringa and Lyrup, in South Australia. The aim of this study was to assess the fish populations and aquatic habitats in the Pike Anabranch system. The specific objectives were to: Determine the distribution and community structure of fish assemblages in the Pike Anabranch system; Determine the distribution and community structure of in-stream habitat in the Pike Anabranch system; and Investigate the relationship between fish assemblages, micro-habitat and meso-habitats (flow types).A total of 16 sites were assessed across the Pike Anabranch system, including three in the main channel of the River Murray. Fish were sampled using an electro-fishing approach and detailed habitat assessments were undertaken at each fish survey site. Quantitative habitat assessments were also carried out for every 90-second electrofishing shot to allow analysis of fish-habitat associations. During the survey, a total of 4138 fish were collected in the Pike Anabranch system and adjacent River Murray representing nine native and four non-native species. The most abundant species were bony herring Nematolosa erebi (n=1524), un-specked hardyhead Craterocephalus stercusmnuscarum fulvus (n=1424), goldfish Carassius auratus (n =442), common carp Cyprinus carpio (n =237) and Australian smelt Retropinna semoni (n =181). Two fish species of specific conservation interest were also captured in low abundance, freshwater catfish Tandanus tandanus and silver perch Bidyanus bidyanus. Both species are protected under the South Australian Fisheries Management Act 2007. Overall, fish species richness was comparatively lower than the species richness recorded in the off-channel habitats of Katarapko and Chowilla Anabranch systems. In addition, the fish community composition of the Pike Anabranch system did not differ between meso-habitat types.In general, riparian habitat within the Pike Anabranch system was poor condition, while in-stream habitat was relatively good and dominated by native taxa. Only a few habitat associations were revealed in some fish species, which may relate to the lack of distinct habitat types in this anabranch system, i.e. low habitat heterogeneity. Generally, the system appears to provide conditions supporting an increase presence of non-native fish species, as opposed to native species, hence the Pike Anabranch system may provide a good template for a habitat restoration approach. Floodplain management activities within the Pike Anabranch systems, such as increasing connectivity and flowing habitats, may facilitate increase native fish diversity and abundance, by increasing the diversity of micro- and meso-habitats.

ObjectivePsychosocial stress is transduced into disease risk through energy-dependent release of hormones that affect target organs, tissues, and cells. The magnitude of the physiological stress responses reflects both systemic levels of these hormones and the sensitivity of target tissues to their effects. Thus, differential expression of receptors across organs likely contributes to stress transduction. Here we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor expression.MethodsWe systematically examined gene expression levels for the glucocorticoid receptor (GR), α- and β-adrenergic receptors (AR-α1B, AR-α2B AR-β2, and AR-β3), across 55 different organs using the Human Protein Atlas dataset. We also leveraged the Human Proteome Map and MitoCarta3.0 data to examine receptor protein levels and, given the energy-dependence of the stress response, the link between stress hormone receptor density and mitochondrial pathways. Finally, we tested the functional interplay between GR activation and AR expression in living human cells.ResultsThe GR was expressed ubiquitously across all investigated organ systems. Immune tissues and cells expressed the highest GR RNA and protein levels. In contrast, AR subtypes showed lower and more localized expression patterns. Co-regulation was found between GR and AR-α1B, as well as between AR-α1B and AR-α2B. In human fibroblasts, activating the GR selectively increased AR-β2 (3.6-fold) and AR-α1B (2.2-fold) expression, confirming their interaction. Consistent with the energetic cost of stress responses, GR and AR expression were positively associated with the expression of key mitochondrial pathways.ConclusionOur results provide a cartography of GR and AR expression across the human body. Tissue-specific stress hormone receptor expression patterns could make specific organ systems more responsive to the sustained, energetically expensive, neuroendocrine signaling pathways triggered by chronic psychosocial stress.

This pre-registration document details the proposed research questions and planned analyses for a secondary data analysis based on data collected from the Adult Health and Behavior (AHAB) project.

The accumulation of day-to-day stressors can impact mental and physical health. How people respond to stressful events is a key mechanism responsible for the effects of stress, and individual differences in stress responses can either perpetuate or prevent negative consequences. Most research on daily stress processes has focused on affective responses to stressors, but stress responses can involve more than just affect. Additionally, most research has been on the role of neuroticism in shaping those responses, but many other individual differences are associated with stress outcomes. In this study, we more comprehensively characterized daily stress processes by expanding the nomological networks of stress responses to include Big Five personality states. We also linked those stress responses to all Big Five traits, as well as individual differences in stress exposure and stress appraisal. We studied a sample of participants (N = 1,090) who reported on stressful events, their appraisal of events in terms of severity and controllability, and their Big Five personality states daily for 7-10 days (N = 8,870 observations). Multi-level structural equation models were used to separate how characteristics of the perceived stressful situation and characteristics of the person play into daily stress processes. Results showed that (1) all Big Five personality states shift in response to perceived stress, (2) all Big Five personality traits relate to average levels of perceived stress exposure and appraisals, (3) individual differences in personality and average perceived stress exposure and perceived severity relate to the strength of personality state responses to daily stress. Our results point to new pathways by which stressors affect people in everyday life and begin to clarify processes that may explain individual differences in risk or resilience to the harmful effects of stress.