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IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Researchers increasingly recognize that the mind and culture interact at many levels to constitute our lived experience, yet we know relatively little about the extent to which culture shapes the way people appraise their experiences and the likelihood that a given experience will be reported. Experiences that involve claims regarding deities, extraordinary abilities, and/or psychopathology offer an important site for investigating the interplay of mind and culture at the population level. However, the difficulties inherent in comparing culture-laden experiences, exacerbated by the siloing of research on experiences based on discipline-specific theoretical constructs, have limited our ability to do so. We introduce the Inventory of Nonordinary Experiences (INOE), which allows researchers to compare experiences by separating the phenomenological features from how they are appraised and asking about both. It thereby offers a new means of investigating the potentially universal (etic) and culture-specific (emic) aspects of lived experiences. To ensure that the INOE survey items are understood as intended by English speakers in the US and Hindi speakers in India, and thus can serve as a basis for cross-cultural comparison, we used the Response Process Evaluation (RPE) method to collect evidence of item-level validity. Our inability to validate some items drawn from other surveys suggests that they are capturing a wider range of experiences than researchers intend. Wider use of the RPE method would increase the likelihood that survey results are due to the differences that researchers intend to measure.

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

[This corrects the article DOI: 10.1371/journal.pone.0245064.].

Immune literacy garnered significant attention in recent years due to the threat posed by emerging infectious diseases. The pace of immunological discoveries and their relevance to society are substantial yet coordinated educational efforts have been rare. This motivated us to create a task force of educators to reflect on pedagogical approaches to teaching immunology and to draft, develop, and evaluate key competencies for undergraduate immunology education. The research questions addressed include: 1) Which competencies are considered important by educators? 2) Are the illustrative skills clear, accurate and well aligned with the core competencies listed in the Vision and Change report?; 3) What are the concerns of immunology educators about competencies and skills? We collected data on the draft competencies using surveys, focus groups, and interviews. The iterative revision phase followed the community review phase before finalizing the framework. Here, we report a hierarchical learning framework, with six core competencies, twenty illustrative skills, and companion immunology-specific example learning outcomes. Predominant themes from interviews and focus groups, which informed revisions of this framework are shared. With the growing need for immunology education across the sciences, the ImmunoSkills Guide and accompanying discussion can be used as a resource for educators, administrators and policymakers.

This study introduces a laser scattering system to protect a low-speed aircraft. Scattering was selected to reduce the laser's intensity targeting the sensor of an aircraft and simultaneously maintaining the functionality of aircraft optics. Mie scattering, known for effectively decreasing short-wave infrared light, was employed by utilizing water aerosols having a diameter of 1 to 5 μm. Experimental results regarding the decrease of the laser intensity via scattering confirmed that the theoretical and experimental values resulted in a similar decrease rate under static conditions. To validate the theoretical values, the path length, which the laser passing through water aerosols, was changed. To assess the system's feasibility in flow conditions, a low-speed wind tunnel was employed to generate two flow speeds: 5.5 m/s and 17.6 m/s. Remarkably, the reduction of laser intensity was only affected by the path length, and was somewhat unaffected regardless of flow speed and the uniformity of the flow, only to the path length. In all cases, the initial laser intensity was set to 10 mW. Under static conditions, the intensity dropped to 8.21 mW, showing a decrease of 17.9%. In flow conditions of 5.5 m/s, 17.6 m/s, and in distorted flow, the laser intensity decreased by 18.3%, 18.1%, and 18% respectively. As a preliminary study, these results demonstrate the system's capability to protect a low-speed aircraft targeted by lasers even under dynamic flow conditions, may suggest a possibility of providing a practical defence solution.

BackgroundNaloxone is critical for reversing opioid-related overdoses. However, there is a dearth of research examining how naloxone possession and carriage are impacted by time-varying individual and social determinants, and if this differed during the height of the COVID-related mitigation measures (e.g., shutdowns).MethodsWe utilized weekly ecological momentary assessments (EMA) to measure factors associated with naloxone possession and carriage among 40 people who use illicit opioids in New York City, for 24 months. Descriptive statistics were used to explore the frequency of weeks with consistent naloxone possession and carriage. Mixed effects binary and multivariable logistic regression was used to test for the impact of time-varying EMA- and baseline-level factors on each outcome.ResultsApproximately 70% of weekly EMAs were associated with consistent naloxone possession or carriage. In multivariable models, compared to during the height of the COVID-related shutdowns (March 12, 2020-May 19, 2021), the time before was associated with lower odds of consistent possession (Odds Ratio (OR) = 0.05, 95% Confidence Interval (CI) = 0.01-0.15) and consistent carriage (OR = 0.06, CI = 0.01-0.25). Additionally, being female (OR = 11.15, CI = 2.85-43.42), being White versus being Black or Hispanic/Latinx (OR = 8.05, CI = 1.96-33.06), and lifetime overdose (OR = 1.96, CI = 1.16-19.80) were associated with higher odds of consistent possession. Recent opioid injection (OR = 3.66, CI = 1.34-9.94), being female (OR = 7.91, CI = 3.91-8.23), and being White (OR = 5.77, CI = 1.35-24.55) were associated with higher odds of consistent carriage. Not wanting to be perceived as a drug user was reported in nearly one third (29.0%; 190/656) of EMAs where inconsistent possession was reported.ConclusionsOur findings paint a relatively positive picture of possession and carriage during COVID-related shutdowns, particularly among white and female participants, and highlight the importance of capturing time-varying factors to understand naloxone-related behavior. To curb growing disparities, outreach to equip Black and Hispanic/Latinx people with naloxone is needed as well as interventions to reduce stigma as a barrier to naloxone engagement.

School is a key site for prevention and early intervention in public mental health, with sexual and gender minority students being a priority group for action. Context is important in understanding how school inclusion of sexual and gender minorities shapes mental health and well-being, with rapidly changing social and political forces necessitating ongoing research. This coproduced UK secondary school-based study aimed to understand (a) key components of mentally, socially and emotionally healthy school environments for LGBTQ+ students considerate of intersecting minoritised identities; (b) staff information, skills and capacity needs and (c) factors influencing uptake and implementation. Online interviews and focus groups were conducted with 63 participants (22 staff, 32 students (aged 13-19 years), and 9 training providers), diverse in relation to gender and sexual identity, ethnicity, religious and social context. Data were analysed thematically. One overarching theme captured the need for an intersectionality-informed, contextually adaptable, whole school approach which 'shifts the narrative' away from deficit thinking, challenging prevailing cis/heteronormative and White norms. This underpinned four themes: (1) 'Feeling safe, seen and celebrated: embedding intersectional signs, signals and symbols', (2) 'Everyone's business: the need for collaboration', (3) 'Embedding a culture of change', and (4) 'Re-locating the problem: challenging deficit thinking'. Contextually diverse research is needed which critically addresses ways in which social power enacted interpersonally and structurally serves to hinder schools from enacting LGBTQ+ inclusivity. Evidence to inform and develop implementation strategies for institutional changes and to advocate for wider socio-political support is also key to mitigate the potential for widening inequities linked to inequitable school environments.

IntroductionPain affects all children, and in hospitals across North America, this pain is often undertreated. Children who visit the emergency department (ED) experience similar undertreatment, and they will often experience a painful procedure as part of their diagnostic journey. Further, children and their caregivers who experience social injustices through marginalization are more likely to experience healthcare disparities in their pain management. Still, most of our knowledge about children's pain management comes from research focused on well-educated, white children and caregivers from a middle- or upper-class background. The aim of this scoping review is to identify, map, and describe existing research on (a) how aspects of marginalization are documented in randomized controlled trials related to children's pain and (b) to understand the pain treatment and experiences of marginalized children and their caregivers in the ED setting.Methods and analysisThe review will follow Joanna Briggs Institute methodology for scoping reviews using the Participant, Concept, Context (PCC) framework and key terms related to children, youth, pain, ED, and aspects of marginalization. We will search Medline, Embase, PsychInfo, CINAHL, Web of Science, Cochrane Library Trials, iPortal, and Native Health Database for articles published in the last 10 years to identify records that meet our inclusion criteria. We will screen articles in a two-step process using two reviewers during the abstract and full-text screening stages. Data will be extracted using Covidence for data management and we will use a narrative approach to synthesize the data.Ethics and disseminationEthical approval is not required for this review. Findings will be disseminated in academic manuscripts, at academic conferences, and with partners and knowledge users including funders of pain research and healthcare professionals. Results of this scoping review will inform subsequent quantitative and qualitative studies regarding pain experiences and treatment of marginalized children in the ED.

Models of invasive species spread often assume that landscapes are spatially homogeneous; thus simplifying analysis but potentially reducing accuracy. We extend a recently developed partial differential equation model for invasive conifer spread to account for spatial heterogeneity in parameter values and introduce a method to obtain key outputs (e.g. spread rates) from computational simulations. Simulations produce patterns of spatial spread which appear qualitatively similar to observed patterns in grassland ecosystems invaded by exotic conifers, validating our spatially explicit strategy. We find that incorporating spatial variation in different parameters does not significantly affect the evolution of invasions (which are characterised by a long quiescent period followed by rapid evolution towards to a constant rate of invasion) but that distributional assumptions can have a significant impact on the spread rate of invasions. Our work demonstrates that spatial variation in site-suitability or other parameters can have a significant impact on invasions and must be considered when designing models of invasive species spread.

BackgroundFollowing traumatic brain injury (TBI) some patients develop lingering comorbid symptoms of fatigue and cognitive impairment. The mild cognitive impairment self-reported by patients is often not detected with neurocognitive tests making it difficult to determine how common and severe these symptoms are in individuals with a history of TBI. This study was conducted to determine the relative prevalence of fatigue and cognitive impairment in individuals with a history of TBI.MethodsThe Fatigue and Altered Cognition Scale (FACs) digital questionnaire was used to assess self-reported fatigue and cognitive impairment. Adults aged 18-70 were digitally recruited for the online anonymous study. Eligible participants provided online consent, demographic data, information about lifetime TBI history, and completed the 20 item FACs questionnaire.ResultsA total of 519 qualifying participants completed the online digital study which included 204 participants with a history of TBI of varied cause and severity and 315 with no history of TBI. FACs Total Score was significantly higher in the TBI group (57.7 ± 22.2) compared to non-TBI (39.5 ± 23.9; pConclusionsAdults with a history of even mild TBI report significantly greater fatigue and cognitive impairment than those with no history of TBI, and symptoms are more profound with greater TBI severity.

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31-60 (n = 110) and 61-90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

Understanding the distribution of lifes variety has driven naturalists and scientists for centuries, yet this has been constrained both by the available data and the models needed for their analysis. Here we compiled data for over 67,000 marine and terrestrial species and used artificial neural networks to model species richness with the state and variability of climate, productivity, and multiple other environmental variables. We find terrestrial diversity is better predicted by the available environmental drivers than is marine diversity, and that marine diversity can be predicted with a smaller set of variables. Ecological mechanisms such as geographic isolation and structural complexity appear to explain model residuals and also identify regions and processes that deserve further attention at the global scale. Improving estimates of the relationships between the patterns of global biodiversity, and the environmental mechanisms that support them, should help in efforts to mitigate the impacts of climate change and provide guidance for adapting to life in the Anthropocene.

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between people with SCD and other congenital anemias who were routinely exposed to blood products during the high-risk period before HIV screening implementation. Non-SCD congenital anemia diagnosis was associated with a higher risk of HIV acquisition compared to SCD (OR 13.1 95%CI 1.6-108.9). In addition, we prospectively enrolled 30 SCD cases and 30 non-SCD controls to investigate potential mechanisms of resistance to HIV in SCD. CCR5 and CCR7 expression was lower and CD4 expression was higher on CD4+ T cells from SCD cases compared to controls. Surface expression of CD4+ T cell CXCR4, CD38 and HLA-DR did not differ between the groups. SCD CD4+ T cells were not less susceptible to HIV infection than controls. Levels of multiple cytokines were elevated in the SCD plasma, but SCD plasma compared to control plasma did not inhibit HIV infection of target cells. In conclusion, our epidemiological data support people with SCD being resistant to HIV infection. Potential mechanisms include lower CD4+ T cell expression of CCR5 and CCR7, balanced by increased CD4 expression and cytokine levels, which did not result in in vitro resistance to HIV infection. Further study is needed to define the risk and pathophysiology of HIV in persons with SCD.

BackgroundSegmented cine cardiac MRI combines data from multiple heartbeats to achieve high spatiotemporal resolution cardiac images, yet predefined k-space segmentation trajectories can lead to suboptimal k-space sampling. In this work, we developed and evaluated an autonomous and closed-loop control system for radial k-space sampling (ARKS) to increase sampling uniformity.MethodsThe closed-loop system autonomously selects radial k-space sampling trajectory during live segmented cine MRI and attempts to optimize angular sampling uniformity by selecting views in regions of k-space that were not previously well-sampled. Sampling uniformity and the ability to detect cardiac phase in vivo was assessed using ECG data acquired from 10 normal subjects in an MRI scanner. The approach was then implemented with a fast gradient echo sequence on a whole-body clinical MRI scanner and imaging was performed in 4 healthy volunteers. The closed-loop k-space trajectory was compared to random, uniformly distributed and golden angle view trajectories via measurement of k-space uniformity and the point spread function. Lastly, an arrhythmic dataset was used to evaluate a potential application of the approach.ResultsThe autonomous trajectory increased k-space sampling uniformity by 15±7%, main lobe point spread function (PSF) signal intensity by 6±4%, and reduced ringing relative to golden angle sampling. When implemented, the autonomous pulse sequence prescribed radial view angles faster than the scan TR (0.98 ± 0.01 ms, maximum = 1.38 ms) and increased k-space sampling mean uniformity by 10±11%, decreased uniformity variability by 44±12%, and increased PSF signal ratio by 6±6% relative to golden angle sampling.ConclusionThe closed-loop approach enables near-uniform radial sampling in a segmented acquisition approach which was higher than predetermined golden-angle radial sampling. This can be utilized to increase the sampling or decrease the temporal footprint of an acquisition and the closed-loop framework has the potential to be applied to patients with complex heart rhythms.

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids.

Archaeological faunal remains provide key insights into human societies in the past, alongside information on previous resource utilisation and exploitation of wildlife populations. The great whales (Mysticete and sperm whales) were hunted unsustainably throughout the 16th - 20th centuries (herein defined as the modern period) leading to large population declines and variable recovery patterns among species. Humans have utilised whales as a resource through carcass scavenging for millennia; however, increasing local and regional ethnographic and archaeological evidence suggests that, prior to the modern period, hunting of the great whales was more common than previously thought; impacts of earlier hunting pressures on the population ecology of many whale species remains relatively unknown. Hunting guided by traditional ecological knowledge may have been sustainable and likely originated in societies that also incorporated opportunistic use of stranded individuals. The collation of georeferenced zooarchaeological data of the great whales between the 1st - 20th centuries CE worldwide will provide insight into the timescale and distribution of resource utilisation of the great whales and how this varied within and between societies, and may have changed over time. By comparing regions of known resource utilisation and breeding and feeding grounds of current-day whale populations, this information will subsequently be used to infer regions where whale populations were possibly lost or extirpated prior to detailed historical records. This systematic review protocol also provides a template for archaeologists, ecologists, and historians interested in using faunal remains to infer historical ecology and resource use of wild animal populations. The transparency of our data collection approach provides opportunities for reproducibility and comparability with future datasets.

Sea cucumbers, belonging to the phylum Echinodermata, are known to possess valuable bioactive compounds that have medicinal properties. In several countries, such as Korea, China, and Japan, they are cultured in the aquaculture industries for food and medicinal purposes. Research has shown that different species of sea cucumbers each possesses unique medicinal values. As a result, we strive towards finding species with better health resilience in aquaculture system to be cultured for nutritional and medicinal purposes. In this paper, we compared the physiological and immunological parameters of three species of sea cucumbers, Cucumaria frondosa (C. frondosa), Isostychopus badionotus (I. badionotus), and Pentacta pygmaea (P. Pygmaea) from the waters of the eastern United States as they have not been studied extensively. Four different cells of sea cucumbers, phagocytic, red spherule, white spherule, and vibratile cells, that contribute to their immunity were counted. C. frondosa exhibited the highest concentrations of phagocytic cells, white spherule cells, and vibratile cells, compared to the two other species. Due to its high phagocytic cell concentration, the highest phagocytic capacity was seen in C. frondosa although it was not statistically significant. We also observed that C. frondosa had the highest total cell count and the highest concentration of coelomic protein among the three species. Lastly, C. frondosa possessed the highest lysozyme activity. Taken together, we concluded that C. frondosa is the best of the three species compared to be reared in the aquaculture systems for use in the food and biomedicine industries due to its immunological and physiological properties.

Rationale Mycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. Objectives The objectives of this study were to assess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection. Methods 7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the M. intracellulare infection were assessed using a series of linear mixed models. Measurements and main results Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14–21 days after inoculation. Conclusion Endobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor's StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthXTM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements necessary for mRNA vaccines. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental conditions which affects just under 1% of the global population. This study aims to investigate the trends in ASD diagnoses in a typical English deprived coastal community over the last two decades. ASD information for patients registered at Fleetwood GP practices were provided for the period between July 1952 to March 2022. The incidence and prevalence were calculated and Poisson regression modelling was employed to estimate the effects of age and sex on the number of ASD diagnoses over time. The study shows that there has been an upward trend in the number of ASD diagnoses over the past two decades. Model's results showed that sex differences in ASD diagnoses are less pronounced when accounting for time trends. The study findings show that Fleetwood has experienced a similar rise in ASD cases as the rest of the UK, most likely due to increased awareness that may explain the time effects over gender differences. However, due to the small sample size of the study, confirmation of the gender results and identification of the factors determining the temporal trends are needed in order to determine the gender effects in ASD diagnosis.

Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.

BackgroundPrognostic variables for assessing people with whiplash associated disorder (WAD) following a motor vehicle collision (MVC) have been evaluated in numerous studies. However, there is minimal evidence assessing how these variables may differ between males and females.Question/purpose1) To assess if the sex of a person interacts with known prognostic variables within the development of chronic WAD. 2) To determine if commonly used outcome measures used in the assessment of chronic WAD differ between sexes.MethodsThe study was a secondary analysis of an observational study with an inception cohort immediately following an MVC in an emergency department in Chicago, IL, USA. Ninety-seven adults aged 18 to 60 (mean 34.7 years old; 74% female) participated in the study. The primary outcome was long-term disability as determined by Neck Disability Index (NDI) scores at 52-weeks post-MVC. Data was collected at baseline (less than 1-week), 2, 12, 52-weeks post MVC. Hierarchal linear regression was used to determine significance (ΔF-score, p < 0.05) and R2 for each of the variables. The primary variables of interest were sex of the participant, age, baseline scores on the numeric pain rating scale (NPRS) and NDI and created interaction terms for sex x z-baseline NPRS and sex x z-NDI.ResultsFrom analysis 1, both NDI (R2 = 8.7%, p < 0.01) and NPRS (R2 = 5.7%, p = 0.02) collected at baseline predicted significant variance in NDI score at 52-weeks. The interaction term of sex x z-NPRS was also significant (R2 = 3.8%, p = 0.04). In analysis 2 the regression models when disaggregated by sex showed that baseline NDI was the significant predictor of 52-week outcome in males (R2 = 22.4%, p = 0.02) while it was the NPRS as the significant predictor in females (R2 = 10.5%, p < 0.01).

BackgroundUnderstanding sources of microbial contamination in outpatient rehabilitation (REHAB) clinics is important to patients and healthcare providers.PurposeThe purpose of this study was to characterize the microbiome of an outpatient REHAB clinic and examine relationships between clinic factors and contamination.MethodsForty commonly contacted surfaces in an outpatient REHAB clinic were observed for frequency of contact and swiped using environmental sample collection kits. Surfaces were categorized based on frequency of contact and cleaning and surface type. Total bacterial and fungal load was assessed using primer sets specific for the 16S rRNA and ITS genes, respectively. Bacterial samples were sequenced using the Illumina system and analyzed using Illumina-utils, Minimum Entropy Decomposition, QIIME2 (for alpha and beta diversity), LEfSe and ANCOM-BC for taxonomic differential abundance and ADONIS to test for differences in beta diversity (pResultsPorous surfaces had more bacterial DNA compared to non-porous surfaces (median non-porous = 0.0016ng/μL, 95%CI = 0.0077-0.00024ng/μL, N = 15; porous = 0.0084 ng/μL, 95%CI = 0.0046-0.019 ng/μL, N = 18. p = 0.0066,DNA. Samples clustered by type of surface with non-porous surfaces further differentiated by those contacted by hand versus foot. ADONIS two-way ANOVA showed that the interaction of porosity and contact frequency (but neither alone) had a significant effect on 16S communities (F = 1.7234, R2 = 0.0609, p = 0.032).DiscussionPorosity of surfaces and the way they are contacted may play an underestimated, but important role in microbial contamination. Additional research involving a broader range of clinics is required to confirm results. Results suggest that surface and contact-specific cleaning and hygiene measures may be needed for optimal sanitization in outpatient REHAB clinics.

Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.

A substantial body of evidence suggests that young people, including those at the crucial transition points between 16 and 24, now face severe mental health challenges. In this article, we analyse data from 10 waves of a major UK longitudinal household cohort study, Understanding Society, to examine the relationship between income and anxiety and depression among 16- to 24-year-olds. Using random effects logistic regression (Model 1) allowing for whether the individual was depressed in the previous period as well as sex, age, ethnicity, whether the individual was born in the UK, region, rurality, highest qualification, marital status, employment status and attrition, we find a significant and inversely monotonic adjusted association between average net equivalised household income quintiles and clinical threshold levels of depressive symptoms SF-12 Mental Component Summary (MCS score ≤45.6). This means that being in a higher income group is associated with a reduced likelihood of clinically significant depressive symptoms, allowing for observable confounding variables. Using a 'within-between' model (Model 2), we find that apart from among those with the very highest incomes, increases in average net equivalised household income over the course of childhood and adolescence are significantly associated with reduced symptoms of anxiety and depression as measured by a higher SF-12 MCS score. Compared with previous reviews, the data presented here provides an estimate of the magnitude of effect that helps facilitate microsimulation modelling of impact on anxiety and depression from changes in socioeconomic circumstances. This enables a more detailed and complete understanding of the types of socioeconomic intervention that might begin to address some of the causes of youth mental health problems.

BackgroundLong COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.MethodsPeople were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.ResultsWe interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.ConclusionThis pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.

Adolescent mental health is impacted by a myriad of factors, including the developing brain, socioeconomic conditions and changing social relationships. Studies to date have neglected investigating those factors simultaneously, despite evidence of their interacting effects and distinct profiles for males and females. The current study addressed that gap by applying structural equation modelling to IMAGEN data from adolescents aged 14 years (n = 1950). A multi-group model split by sex was tested with the variables of socioeconomic stress, family support, peer problems, and brain structure as predictors, and emotional symptoms as the main outcome. Findings indicated that, for both sexes, peer problems were positively associated with emotional symptoms, and socioeconomic stress was negatively associated with family support. Additionally, there were sex-specific findings within the full models: ventromedial prefrontal cortex grey matter volume was negatively associated with emotional symptoms for males when corrected for whole brain volume, and socioeconomic stress was negatively associated with whole brain volume for females. This study underscores the importance of the peer environment for early adolescent emotional symptoms in both boys and girls, but goes further to suggest distinct gender associations with socioeconomic factors and brain structure which provides a multi-level view of risk and resilience. Future research could exploit existing IMAGEN longitudinal data to strengthen causal claims and to determine the potential longstanding impact of social environment and brain development on adolescent mental health.

There is extensive laboratory research studying the effects of acute sleep deprivation on biological and cognitive functions, yet much less is known about naturalistic patterns of sleep loss and the potential impact on daily or weekly functioning of an individual. Longitudinal studies are needed to advance our understanding of relationships between naturalistic sleep and fluctuations in human health and performance, but it is first necessary to understand the efficacy of current tools for long-term sleep monitoring. The present study used wrist actigraphy and sleep log diaries to obtain daily measurements of sleep from 30 healthy adults for up to 16 consecutive weeks. We used non-parametric Bland-Altman analysis and correlation coefficients to calculate agreement between subjectively and objectively measured variables including sleep onset time, sleep offset time, sleep onset latency, number of awakenings, the amount of wake time after sleep onset, and total sleep time. We also examined compliance data on the submission of daily sleep logs according to the experimental protocol. Overall, we found strong agreement for sleep onset and sleep offset times, but relatively poor agreement for variables related to wakefulness including sleep onset latency, awakenings, and wake after sleep onset. Compliance tended to decrease significantly over time according to a linear function, but there were substantial individual differences in overall compliance rates. There were also individual differences in agreement that could be explained, in part, by differences in compliance. Individuals who were consistently more compliant over time also tended to show the best agreement and lower scores on behavioral avoidance scale (BIS). Our results provide evidence for convergent validity in measuring sleep onset and sleep offset with wrist actigraphy and sleep logs, and we conclude by proposing an analysis method to mitigate the impact of non-compliance and measurement errors when the two methods provide discrepant estimates.

Many analyses of fishery recovery have demonstrated the potential biological and economic benefits of management reform, but few have compared these to the associated costs of management upgrades, which can be substantial. This study aims to determine if the projected economic benefits of management reform outweigh the increases in management costs required to achieve those benefits. To answer this question, we developed a database of country-level fisheries management costs and use those to estimate the country-level costs of management changes. We use this framework to compare estimates of future costs of management upgrades against their economic benefits in terms of profit. Results indicate that for most nations, including the top 25 fishing nations, management upgrades outweigh their associated costs. This result is robust to a number of alternative assumptions about costs. Results also suggest that stronger reforms such as rights-based management, although sometimes more expensive to implement, can lead to greater net economic benefits compared to alternatives.

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice.

A hallmark of human immunosenescence is the accumulation of late-differentiated memory CD8+ T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, enhanced activation, and increased secretion of inflammatory cytokines. Importantly, oligoclonal expansions of these cells are associated with increased morbidity and mortality risk in elderly humans. Currently, most information on the adaptive immune system is derived from studies using peripheral blood, which contains approximately only 2% of total body lymphocytes. However, most lymphocytes reside in tissues. It is not clear how representative blood changes are of the total immune status. This is especially relevant with regard to the human gastrointestinal tract (GALT), a major reservoir of total body lymphocytes (approximately 60%) and an anatomical region of high antigenic exposure. To assess how peripheral blood T cells relate to those in other locations, we compare CD8+ T cells from peripheral blood and the GALT, specifically rectosigmoid colon, in young/middle age, healthy donors, focusing on phenotypic and functional alterations previously linked to senescence in peripheral blood. Overall, our results indicate that gut CD8+ T cells show profiles suggestive of greater differentiation and activation than those in peripheral blood. Specifically, compared to blood from the same individual, the gut contains significantly greater proportions of CD8+ T cells that are CD45RA- (memory), CD28-, CD45RA-CD28+ (early memory), CD45RA-CD28- (late memory), CD25-, HLA-DR+CD38+ (activated) and Ki-67+ (proliferating); ex vivo CD3+ telomerase activity levels are greater in the gut as well. However, gut CD8+ T cells may not necessarily be more senescent, since they expressed significantly lower levels of CD57 and PD-1 on CD45RO+ memory cells, and had in vitro proliferative dynamics similar to that of blood cells. Compartment-specific age-effects in this cohort were evident as well. Blood cells showed a significant increase with age in proportion of HLA-DR+38+, Ki-67+ and CD25+ CD8+ T cells; and an increase in total CD3+ ex-vivo telomerase activity that approached significance. By contrast, the only age-effect seen in the gut was a significant increase in CD45RA- (memory) and concurrent decrease in CD45RA+CD28+ (naïve) CD8+ T cells. Overall, these results indicate dynamics of peripheral blood immune senescence may not hold true in the gut mucosa, underscoring the importance for further study of this immunologically important tissue in evaluating the human immune system, especially in the context of chronic disease and aging.

Wearable devices are a popular training tool to measure biomechanical performance indicators during running, including vertical oscillation (VO). VO is a contributing factor in running economy and injury risk, therefore VO feedback can have a positive impact on running performance. The validity and reliability of the VO measurements from wearable devices is crucial for them to be an effective training tool. The aims of this study were to test the validity and reliability of VO measurements from wearable devices against video analysis of a single trunk marker. Four wearable devices were compared: the INCUS NOVA, Garmin Heart Rate Monitor-Pro (HRM), Garmin Running Dynamics Pod (RDP), and Stryd Running Power Meter Footpod (Footpod). Fifteen participants completed treadmill running at five different self-selected speeds for one minute at each speed. Each speed interval was completed twice. VO was recorded simultaneously by video and the wearables devices. There was significant effect of measurement method on VO (p < 0.001), with the NOVA and Footpod underestimating VO compared to video analysis, while the HRM and RDP overestimated. Although there were significant differences in the average VO values, all devices were significantly correlated with the video analysis (R > = 0.51, p < 0.001). Significant agreement between repeated VO measurements for all devices, revealed the devices to be reliable (ICC > = 0.948, p < 0.001). There was also significant agreement for VO measurements between each device and the video analysis (ICC > = 0.731, p < = 0.001), therefore validating the devices for VO measurement during running. These results demonstrate that wearable devices are valid and reliable tools to detect changes in VO during running. However, VO measurements varied significantly between the different wearables tested and this should be considered when comparing VO values between devices.

Rapid identification of potentially life-threatening blood stream infections (BSI) improves clinical outcomes, yet conventional blood culture (BC) identification methods require ~24-72 hours of liquid culture, plus 24-48 hours to generate single colonies on solid media suitable for identification by mass spectrometry (MS). Newer rapid centrifugation techniques, such as the Bruker MBT-Sepsityper® IVD, replace culturing on solid media and expedite the diagnosis of BCs but frequently demonstrate reduced sensitivity for identifying clinically significant Gram-positive bacterial or fungal infections. This study introduces a protocol that utilises the broad-range binding properties of an engineered version of mannose-binding lectin linked to the Fc portion of immunoglobulin (FcMBL) to capture and enrich pathogens combined with matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) MS for enhanced infection identification in BCs. The FcMBL method identified 94.1% (64 of 68) of clinical BCs processed, with a high sensitivity for both Gram-negative and Gram-positive bacteria (94.7 and 93.2%, respectively). The FcMBL method identified more patient positive BCs than the Sepsityper® (25 of 25 vs 17 of 25), notably with 100% (3/3) sensitivity for clinical candidemia, compared to only 33% (1/3) for the Sepsityper®. Additionally, during inoculation experiments, the FcMBL method demonstrated a greater sensitivity, identifying 100% (24/24) of candida to genus level and 9/24 (37.5%) top species level compared to 70.8% (17/24) to genus and 6/24 to species (25%) using the Sepsityper®. This study demonstrates that capture and enrichment of samples using magnetic FcMBL-conjugated beads is superior to rapid centrifugation methods for identification of BCs by MALDI-TOF MS. Deploying the FcMBL method therefore offers potential clinical benefits in sensitivity and reduced turnaround times for BC diagnosis compared to the standard Sepsityper® kit, especially for fungal diagnosis.

BackgroundT2D is an increasingly common disease that is associated with worse outcomes in patients with heart failure. Despite this, no contemporary study has assessed its impact on heart transplantation outcomes. This paper examines the demographics and outcomes of patients with type 2 diabetes (T2D) undergoing heart transplantation.MethodsUsing the United Network for Organ Sharing (UNOS) database, patients listed for transplant were separated into cohorts based on history of T2D. Demographics and comorbidities were compared, and cox regressions were used to examine outcomes.ResultsBetween January 1st, 2011 and June 12th, 2020, we identified 9,086 patients with T2D and 23,676 without T2D listed for transplant. The proportion of patients with T2D increased from 25.2% to 27.9% between 2011 and 2020. Patients with T2D were older, more likely to be male, less likely to be White, and more likely to pay with public insurance (pConclusionsOver the last ten years, the proportion of heart transplant recipients with T2D has increased. These patients are more likely to be from traditionally underserved populations. Patients with T2D have a lower likelihood of transplantation and a higher likelihood of post-transplant mortality. After the allocation system change, likelihood of transplantation has improved for patients with T2D.

Introduction Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled “Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury” is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. Methods and analysis Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. Ethics and dissemination Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.

The objective of this study was to compare the hydrological performance of an irrigated, 127 mm deep green roof, planted with vegetation native to the New York City area, to a conventional, non-irrigated, 100 mm deep green roof, planted with drought-tolerant Sedum spp. Four years of climate and runoff data from both green roofs were analyzed to determine seasonal stormwater retention. Empirical relationships between rainfall and runoff were developed for both roofs, and applied to historical rainfall data in order to compare stormwater retention values for different rainfall depths. Crop coefficients for the vegetation on each green roof were estimated using the soil moisture extraction function. This function was also used to estimate monthly evapotranspiration. Despite being irrigated, the green roof with native vegetation retained more stormwater per annum (64%) than the non-irrigated green roof planted with Sedum spp. (54%). The green roof planted with native vegetation also had approximately twice the crop coefficient (1.13) than the green roof planted with Sedum spp. (0.57), indicating that the New York City native plants transpire more stormwater than the Sedum spp. plants given certain climate and substrate moisture conditions. Overall, the results of the study indicate that, for the New York City climate region, irrigated green roofs of native vegetation have the capacity to better manage stormwater than non-irrigated green roofs planted with drought-tolerant succulents.

BackgroundThe COVID-19 pandemic has presented a unique opportunity to explore how health systems adapt under rapid and constant change and develop a better understanding of health system transformation. Learning health systems (LHS) have been proposed as an ideal structure to inform a data-driven response to a public health emergency like COVID-19. The aim of this study was to use a LHS framework to identify assets and gaps in health system pandemic planning and response during the initial stages of the COVID-19 pandemic at a single Canadian Health Centre.MethodsThis paper reports the data triangulation stage of a concurrent triangulation mixed methods study which aims to map study findings onto the LHS framework. We used a triangulation matrix to map quantitative (textual and administrative sources) and qualitative (semi-structured interviews) data onto the seven characteristics of a LHS and identify assets and gaps related to health-system receptors and research-system supports.ResultsWe identified several health system assets within the LHS characteristics, including appropriate decision supports and aligned governance. Gaps were identified in the LHS characteristics of engaged patients and timely production and use of research evidence.ConclusionThe LHS provided a useful framework to examine COVID-19 pandemic response measures. We highlighted opportunities to strengthen the LHS infrastructure for rapid integration of evidence and patient experience data into future practice and policy changes.

Early research on the impact of COVID-19 on academic scientists suggests that disruptions to research, teaching, and daily work life are not experienced equally. However, this work has overwhelmingly focused on experiences of women and parents, with limited attention to the disproportionate impact on academic work by race, disability status, sexual identity, first-generation status, and academic career stage. Using a stratified random survey sample of early-career academics in four science disciplines (N = 3,277), we investigated socio-demographic and career stage differences in the effect of the COVID-19 pandemic along seven work outcomes: changes in four work areas (research progress, workload, concern about career advancement, support from mentors) and work disruptions due to three COVID-19 related life challenges (physical health, mental health, and caretaking). Our analyses examined patterns across career stages as well as separately for doctoral students and for postdocs/assistant professors. Overall, our results indicate that scientists from marginalized (i.e., devalued) and minoritized (i.e., underrepresented) groups across early career stages reported more negative work outcomes as a result of COVID-19. However, there were notable patterns of differences depending on the socio-demographic identities examined. Those with a physical or mental disability were negatively impacted on all seven work outcomes. Women, primary caregivers, underrepresented racial minorities, sexual minorities, and first-generation scholars reported more negative experiences across several outcomes such as increased disruptions due to physical health symptoms and additional caretaking compared to more privileged counterparts. Doctoral students reported more work disruptions from life challenges than other early-career scholars, especially those related to health problems, while assistant professors reported more negative changes in areas such as decreased research progress and increased workload. These findings suggest that the COVID-19 pandemic has disproportionately harmed work outcomes for minoritized and marginalized early-career scholars. Institutional interventions are required to address these inequalities in an effort to retain diverse cohorts in academic science.

IntroductionThe Australian National COVID-19 Clinical Evidence Taskforce is producing living, evidence-based, national guidelines for treatment of people with COVID-19 which are updated each week. To continually improve the process and outputs of the Taskforce, and inform future living guideline development, we undertook a concurrent process evaluation examining Taskforce activities and experience of team members and stakeholders during the first 5 months of the project.MethodsThe mixed-methods process evaluation consisted of activity and progress audits, an online survey of all Taskforce participants; and semi-structured interviews with key contributors. Data were collected through five, prospective 4-weekly timepoints (beginning first week of May 2020) and three, fortnightly retrospective timepoints (March 23, April 6 and 20). We collected and analysed quantitative and qualitative data.ResultsAn updated version of the guidelines was successfully published every week during the process evaluation. The Taskforce formed in March 2020, with a nominal start date of March 23. The first version of the guideline was published two weeks later and included 10 recommendations. By August 24, in the final round of the process evaluation, the team of 11 staff, working with seven guideline panels and over 200 health decision-makers, had developed 66 recommendations addressing 58 topics. The Taskforce website had received over 200,000 page views. Satisfaction with the work of the Taskforce remained very high (>90% extremely or somewhat satisfied) throughout. Several key strengths, challenges and methods questions for the work of the Taskforce were identified.ConclusionsIn just over 5 months of activity, the National COVID-19 Clinical Evidence Taskforce published 20 weekly updates to the evidence-based national treatment guidelines for COVID-19. This process evaluation identified several factors that enabled this achievement (e.g. an extant skill base in evidence review and convening), along with challenges that needed to be overcome (e.g. managing workloads, structure and governance) and methods questions (pace of updating, and thresholds for inclusion of evidence) which may be useful considerations for other living guidelines projects. An impact evaluation is also being conducted separately to examine awareness, acceptance and use of the guidelines.

The objective of this study is to optimize the cryopreservation of dissociated islet cells and obtain functional cells that can be used in single-cell transcriptome studies on the pathology and treatment of diabetes. Using an iterative graded freezing approach we obtained viable cells after cooling in 10% dimethyl sulfoxide and 6% hydroxyethyl starch at 1°C/min to –40°C, storage in liquid nitrogen, rapid thaw, and removal of cryoprotectants by serial dilution. The expression of epithelial cell adhesion molecule declined immediately after thaw, but recovered after overnight incubation, while that of an endocrine cell marker (HPi2) remained high after cryopreservation. Patch-clamp electrophysiology revealed differences in channel activities and exocytosis of various islet cell types; however, exocytotic responses, and the biophysical properties of voltage-gated Na+ and Ca2+ channels, are sustained after cryopreservation. Single-cell RNA sequencing indicates that overall transcriptome and crucial exocytosis genes are comparable between fresh and cryopreserved dispersed human islet cells. Thus, we report an optimized procedure for cryopreserving dispersed islet cells that maintained their membrane integrity, along with their molecular and functional phenotypes. Our findings will not only provide a ready source of cells for investigating cellular mechanisms in diabetes but also for bio-engineering pseudo-islets and islet sheets for modeling studies and potential transplant applications.

BackgroundPneumonia and sepsis are among the most common causes of hospitalization in the United States and often result in discharges to a skilled nursing facility (SNF) for rehabilitation. We described the timing and most common causes of 30-day unplanned hospital readmission following an index hospitalization for pneumonia or sepsis.Methods and findingsThis national retrospective cohort study included adults ≥65 years who were hospitalized for pneumonia or sepsis and were discharged to a SNF between July 1, 2012 and July 4, 2015. We quantified the ten most common 30-day unplanned readmission diagnoses and estimated the daily risk of first unplanned rehospitalization for four causes of readmission (circulatory, infectious, respiratory, and genitourinary). The index hospitalization was pneumonia for 92,153 SNF stays and sepsis for 452,254 SNF stays. Of these SNF stays, 20.9% and 25.9%, respectively, resulted in a 30-day unplanned readmission. Overall, septicemia was the single most common readmission diagnosis for residents with an index hospitalization for pneumonia (16.7% of 30-day readmissions) and sepsis (22.4% of 30-day readmissions). The mean time to unplanned readmission was approximately 14 days overall. Respiratory causes displayed the highest daily risk of rehospitalization following index hospitalizations for pneumonia, while circulatory and infectious causes had the highest daily risk of rehospitalization following index hospitalizations for sepsis. The day of highest risk for readmission occurred within two weeks of the index hospitalization discharge, but the readmission risk persisted across the 30-day follow-up.ConclusionAmong older adults discharged to SNFs following a hospitalization for pneumonia or sepsis, hospital readmissions for infectious, circulatory, respiratory, and genitourinary causes occurred frequently throughout the 30-day post-discharge period. Our data suggests further study is needed, perhaps on the value of closer monitoring in SNFs post-hospital discharge and improved communication between hospitals and SNFs, to reduce the risk of potentially preventable hospital readmissions.