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BackgroundCOVID-19's pulmonary manifestations are broad, ranging from pneumonia with no supplemental oxygen requirements to acute respiratory distress syndrome (ARDS) with acute respiratory failure (ARF). In response, new oxygenation strategies and therapeutics have been developed, but their large-scale effects on outcomes in severe COVID-19 patients remain unknown. Therefore, we aimed to examine the trends in mortality, mechanical ventilation, and cost over the first six months of the pandemic for adult COVID-19 patients in the US who developed ARDS or ARF.Methods and findingsThe Vizient Clinical Data Base, a national database comprised of administrative, clinical, and financial data from academic medical centers, was queried for patients ≥ 18-years-old with COVID-19 and either ARDS or ARF admitted between 3/2020-8/2020. Demographics, mechanical ventilation, length of stay, total cost, mortality, and discharge status were collected. Mann-Kendall tests were used to assess for significant monotonic trends in total cost, mechanical ventilation, and mortality over time. Chi-square tests were used to compare mortality rates between March-May and June-August. 110,223 adult patients with COVID-19 ARDS or ARF were identified. Mean length of stay was 12.1±13.3 days and mean total cost was $35,991±32,496. Mechanical ventilation rates were 34.1% and in-hospital mortality was 22.5%. Mean cost trended downward over time (p = 0.02) from $55,275 (March) to $18,211 (August). Mechanical ventilation rates trended down (p

Modeling of background radiation for the urban environment plays an important role in homeland security. However, background radiation is difficult to assess due to its spatial-temporal fluctuations caused by the variation in soil composition, building materials, and weather patterns etc. To address the challenge of background radiation modeling, we developed a mobile sensor network to continuously monitor the background radiation; we also proposed a maximum likelihood estimation algorithm to decouple and estimate the backgrounds spatial distribution and temporal fluctuation. Experimental results demonstrated how this background radiation monitoring system accurately recognized high background regions in the experimental area, and successfully captured temporal fluctuation trends of background radiation during rains. Our system provides an efficient solution to model the temporal fluctuation and spatial distribution of background radiation.

Though citizen science programs have been broadly successful in diverse scientific fields, their adoption has lagged in some disciplines, including soil science and ecosystem ecology. Collaborations with citizen scientists may be viewed as a conundrum in these disciplines, which often require substantial labor and technical experience; citizen scientists could improve sampling capacity but may reduce sample quality or require training and oversight prior to and while performing specialized tasks. To demonstrate the feasibility of incorporating citizen scientists into soil biogeochemistry research, we conducted a proof-of-concept study in high-elevation meadows of the Sierra Nevada in California. A collaboration between university researchers and citizen scientists allowed us to assess spatial and diel patterns of soil greenhouse gas (GHG) fluxes with an intensity and frequency that would otherwise be beyond the capacity of a typical research laboratory. This collaboration with citizen scientists increased our sampling intensity by over 700% while only doubling the sampling error relative to that of full-time researchers. With training and support from project scientists, citizen scientists collected data that demonstrate spatial independence of carbon dioxide, methane, and nitrous oxide at scales between 1 m and 175 m. Additionally, we found a lack of temporal variation over a 24-h period for all three GHGs. Citizen scientists participating in this one-day event reported levels of satisfaction commensurate with longer-term, immersive campaigns. The place-based event also proved an effective tool for teaching intangible concepts of soil biogeochemistry and promoting local conservation. Despite perceived barriers to entry, this study demonstrates the mutual benefits of citizen science collaborations in soil science and ecosystem ecology, encouraging adoption by disciplines that have been slow to take advantage of such collaborations. Short-term, local citizen science events can provide meaningful experiences for area residents and teach global biogeochemical cycles in a place-based context.

Though citizen science programs have been broadly successful in diverse scientific fields, their adoption has lagged in some disciplines, including soil science and ecosystem ecology. Collaborations with citizen scientists may be viewed as a conundrum in these disciplines, which often require substantial labor and technical experience; citizen scientists could improve sampling capacity but may reduce sample quality or require training and oversight prior to and while performing specialized tasks. To demonstrate the feasibility of incorporating citizen scientists into soil biogeochemistry research, we conducted a proof-of-concept study in high-elevation meadows of the Sierra Nevada in California. A collaboration between university researchers and citizen scientists allowed us to assess spatial and diel patterns of soil greenhouse gas (GHG) fluxes with an intensity and frequency that would otherwise be beyond the capacity of a typical research laboratory. This collaboration with citizen scientists increased our sampling intensity by over 700% while only doubling the sampling error relative to that of full-time researchers. With training and support from project scientists, citizen scientists collected data that demonstrate spatial independence of carbon dioxide, methane, and nitrous oxide at scales between 1 m and 175 m. Additionally, we found a lack of temporal variation over a 24-h period for all three GHGs. Citizen scientists participating in this one-day event reported levels of satisfaction commensurate with longer-term, immersive campaigns. The place-based event also proved an effective tool for teaching intangible concepts of soil biogeochemistry and promoting local conservation. Despite perceived barriers to entry, this study demonstrates the mutual benefits of citizen science collaborations in soil science and ecosystem ecology, encouraging adoption by disciplines that have been slow to take advantage of such collaborations. Short-term, local citizen science events can provide meaningful experiences for area residents and teach global biogeochemical cycles in a place-based context.

BackgroundIntrauterine growth restriction (IUGR) results from a lack of nutrients transferred to the developing fetus, particularly oxygen and glucose. Increased expression of the cytoprotective mitochondrial peptide, humanin (HN), and the glucose transporter 8, GLUT8, has been reported under conditions of hypoxic stress. However, the presence and cellular localization of HN and GLUT8 in IUGR-related placental pathology remain unexplored. Thus, we undertook this study to investigate placental expression of HN and GLUT8 in IUGR-affected versus normal pregnancies.ResultsWe found 1) increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for gestational age) pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells.ConclusionsThere was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

ObjectiveTo describe the frequency of being partnered and having an HIV-negative partner, and whether this differed by gender, among a cohort of persons living with HIV (PLWH) who have ever injected drugs; to describe awareness of HIV pre-exposure prophylaxis (PrEP) and perceived partner interest in PrEP.SettingSecondary analyses of an observational cohort study of PLWH who have ever injected drugs in St. Petersburg, Russia.MethodsPrimary outcomes were 1) being partnered and 2) being in a serodiscordant partnership. The main independent variable was gender. Multivariable GEE logistic regression models were fit for binary outcomes, adjusted for age, income, education, and recent opioid use. Descriptive analyses were performed for partners' HIV status, substance use, sex risk behaviors, and awareness of PrEP for a subset of participants.ResultsAt baseline, 50% (147/296) reported being in a partnership, and of those, 35% were in a serodiscordant partnership. After adjustment, women had significantly higher odds of being partnered compared to men (aOR = 3.12; 95% CI: 1.77, 5.51), but there were no significant gender differences in the odds of being in a serodiscordant partnership (aOR = 0.58; 95% CI: 0.27, 1.24). Among a sub-sample of participants queried (n = 56), 25% were aware of PrEP for prevention of sexual HIV transmission and 14% for prevention of injection-related transmission.ConclusionAlthough half of our sample were partnered and one third of these partnerships were serodiscordant, PrEP awareness was low. Substantial opportunities for HIV prevention exist among PLWH who have ever injected drugs in Russia and their HIV-negative partners. Given the high proportion of HIV-negative partners among this ART-naïve sample, efforts to address the associated inherent risks, such as couples-based interventions, are needed to increase condom use, PrEP awareness, or uptake of other HIV-prevention modalities (e.g., ART for the HIV-positive partner).

BackgroundRetinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.MethodsVariant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.Results and conclusionsA total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A>G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon.

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels.

Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg) or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP), neurofilament 200 (NF200) and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.

The Au’au Channel between the islands of Maui and Lanai, Hawaii comprises critical breeding habitat for humpback whales(Megaptera novaeangliae) of the Central North Pacific stock. However, like many regions where marine mega-fauna gather,these waters are also the focus of a flourishing local eco-tourism and whale watching industry. Our aim was to establishcurrent trends in habitat preference in female-calf humpback whale pairs within this region, focusing specifically on thebusy, eastern portions of the channel. We used an equally-spaced zigzag transect survey design, compiled our results in aGIS model to identify spatial trends and calculated Neu’s Indices to quantify levels of habitat use. Our study revealed thatwhile mysticete female-calf pairs on breeding grounds typically favor shallow, inshore waters, female-calf pairs in the Au’auChannel avoided shallow waters (,20 m) and regions within 2 km of the shoreline. Preferred regions for female-calf pairscomprised water depths between 40–60 m, regions of rugged bottom topography and regions that lay between 4 and6 km from a small boat harbor (Lahaina Harbor) that fell within the study area. In contrast to other humpback whalebreeding grounds, there was only minimal evidence of typical patterns of stratification or segregation according to groupcomposition. A review of habitat use by maternal females across Hawaiian waters indicates that maternal habitat choicevaries between localities within the Hawaiian Islands, suggesting that maternal females alter their use of habitat accordingto locally varying pressures. This ability to respond to varying environments may be the key that allows wildlife species topersist in regions where human activity and critical habitat overlap.

The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C) receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.

BackgroundDespite the effectiveness of prophylaxis, Pneumocystis jirovecii pneumonia (PCP) continues to be the most common serious opportunistic infection among HIV-infected persons. We describe factors associated with nonadherence to primary PCP prophylaxis.Methodology/principal findingsWe used 2000-2004 data from the Supplement to HIV/AIDS Surveillance (SHAS) project, a cross-sectional interview project of HIV-infected persons >or=18 years conducted in 18 states. We limited the analysis to persons who denied having prior PCP, reported having a current prescription to prevent PCP, and answered the question "In the past 30 days, how often were you able to take the PCP medication(s) exactly the way your doctor told you to take them?" We used multivariable logistic regression to describe factors associated with nonadherence. Of 1,666 subjects prescribed PCP prophylaxis, 305 (18.3%) were nonadherent. Persons were more likely to be nonadherent if they reported using marijuana (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI] = 1.1-2.4), non-injection drugs other than marijuana (aOR = 1.5, 95% CI = 1.0-2.1), or injection drugs (aOR = 2.3, 95% CI = 1.3-4.1) in the past year; their mental health was "not good" for >or=1 day during the past month (aOR = 1.6, 95% CI = 1.2-2.2); their most recent CD4 count was

The aim of this study was to achieve consensus from leading sport and exercise science practitioners in professional soccer academies surrounding (i) motivations for maturity-related data collection (ii) maturity-related injury risk factors (iii) how maturity-related data informs injury prevention practices and (iv) the use of bio-banding as an alternative injury prevention strategy. The study adopted an iterative three round online Delphi method, where a series of statements were rated by expert panellists. Consensus agreement was set at ≥70% for all statements. Nine panellists participated in all three rounds (69% response rate). Consensus was achieved for a total of sixteen statements. Panellists agreed that the period during and 12-months post peak height velocity, muscle strength/flexibility imbalances and maturity status (% predicted adult height) as the most important maturity-related injury risk factors. Panellists also agreed that maturity-related data collection is important for injury prevention as well as physical and performance-related purposes, but not for recruitment or retain/release purposes. It was also evident that variability and misunderstanding of key language terms used within the growth and maturation literature exists. It was agreed that practitioners who are responsible for conducting maturational assessments require additional training/education to enhance their application, delivery and outcomes. The findings indicate that maturity-related data collection is part of a multidisciplinary process, dedicated towards the long-term development of players. Greater training and education are required along with increased dissemination of research findings surrounding the full uses for bio-banding. This study provides guidance on maturity-related injury risks and prevention in youth soccer for practitioners.

Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents.

BackgroundDisordered sleep and persistent musculoskeletal pain are highly comorbid. Behavioural interventions such as Cognitive Behavioural Therapy for Insomnia (CBT-I) have shown promise in the management of both disordered sleep and persistent musculoskeletal pain. The aim of this review was to examine how CBT-I is delivered in randomised controlled trials involving people with comorbid disordered sleep and persistent musculoskeletal pain.MethodsThe protocol for this scoping review was registered with the Open Science Framework. Electronic searches of ten database and three clinical trials registries were performed up to 25 October 2023. The methodological quality of each study was evaluated by two independent reviewers using the PEDro tool. The reporting of CBT-I interventions was evaluated using the Template for Intervention Description and Replication (TIDieR) checklist.ResultsTwelve studies met the eligibility criteria. TIDieR scores ranged from 7-11/12, with a mean score of 8.8/12. CBT-I always involved two core components-sleep restriction and stimulus control. Furthermore, an additional five components were usually involved-a cognitive component, sleep hygiene, sleep education, relaxation/deactivation procedures and relapse planning. There was also considerable consistency in the frequency (weekly) and duration (5-9 weeks) of CBT-I programmes. Aspects inconsistently reported included who delivered the intervention; what modifications were made, if any; and the session content and duration. PEDro scores ranged from 5-8/10, with a mean score of 6.7/10.ConclusionsThese findings demonstrate considerable consistency in the components of CBT-I delivered in clinical trials along with the number of sessions. The frequency of sessions was also consistent where almost all studies held weekly session. However, some aspects were either not reported (e.g., precise content of components) or inconsistent (e.g., use of terminology). CBT-I was delivered both individually and in groups. Greater consistency, and more detailed reporting regarding who delivered the intervention, the training provided, and the specific content of CBT-I components would add clarity, and may enhance CBT-I efficacy and allow better replication.

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7-10 days post-infection. To evaluate the potential for ADE, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2.

IntroductionOur study seeks to understand the profiles of otolaryngologists selected by Castle Connolly's Top Doctor list and how this compares to the entire field of otolaryngology.MethodsTop Doctor lists published in Castle Connolly affiliated magazines were analyzed for Otolaryngology, Otolaryngology/Facial Plastic Surgery, or Pediatric Otolaryngology physicians. Only lists published in 2021 or representing the 2021 Top Doctor lists were analyzed. Of the total 39 partnered magazines, 27 met our criteria. Information on the physician was analyzed from the Castle Connolly website and included: gender, education, faculty position, years as a Top Doctor, and certifications of each physician.Results879 doctors, 742 (84%) men and 137 women (16%), were included in our analysis. 509 physicians completed a fellowship, 85 (62%) women and 424 (57%) men. The fellowship type varied significantly between gender (p = .002). 122 (14%) Top Doctors completed facial and plastic reconstructive surgery and 111 (91%) were men. Of the women Top Doctors completing a fellowship, 29 (34%) completed a fellowship in pediatric otolaryngology. A logistic regression found that men have an increased odds of being on the Top Doctors list for more years than females (OR: 1.36, p < .001).ConclusionThe percentage of women named as Top Doctors was less than the proportion of women in otolaryngology. This may be attributed to gender differences we found in fellowship type and certification. Further research into the role of otolaryngology subspecialties in selection of Top Doctors is needed to better understand gender differences.

Recent advances in quantitative tools for examining urban morphology enable the development of morphometrics that can characterize the size, shape, and placement of buildings; the relationships between them; and their association with broader patterns of development. Although these methods have the potential to provide substantial insight into the ways in which neighborhood morphology shapes the socioeconomic and demographic characteristics of neighborhoods and communities, this question is largely unexplored. Using building footprints in five of the ten largest U.S. metropolitan areas (Atlanta, Boston, Chicago, Houston, and Los Angeles) and the open-source R package, foot, we examine how neighborhood morphology differs across U.S. metropolitan areas and across the urban-exurban landscape. Principal components analysis, unsupervised classification (K-means), and Ordinary Least Squares regression analysis are used to develop a morphological typology of neighborhoods and to examine its association with the spatial, socioeconomic, and demographic characteristics of census tracts. Our findings illustrate substantial variation in the morphology of neighborhoods, both across the five metropolitan areas as well as between central cities, suburbs, and the urban fringe within each metropolitan area. We identify five different types of neighborhoods indicative of different stages of development and distributed unevenly across the urban landscape: these include low-density neighborhoods on the urban fringe; mixed use and high-density residential areas in central cities; and uniform residential neighborhoods in suburban cities. Results from regression analysis illustrate that the prevalence of each of these forms is closely associated with variation in socioeconomic and demographic characteristics such as population density, the prevalence of multifamily housing, and income, race/ethnicity, homeownership, and commuting by car. We conclude by discussing the implications of our findings and suggesting avenues for future research on neighborhood morphology, including ways that it might provide insight into issues such as zoning and land use, housing policy, and residential segregation.

Using logistic regression and neural networks, the aim of this study was to compare model performance when predicting player draft outcome during the 2021 AFL National Draft. Physical testing, in-game movement and technical involvements were collected from 708 elite-junior Australian Rules football players during consecutive seasons. Predictive models were generated using data from 465 players (2017 to 2020). Data from 243 players were then used to prospectively predict the 2021 AFL National Draft. Logistic regression and neural network models were compared for specificity, sensitivity and accuracy using relative cut-off thresholds from 5% to 50%. Using factored and unfactored data, and a range of relative cut-off thresholds, neural networks accounted for 73% of the 40 best performing models across positional groups and data configurations. Neural networks correctly classified more drafted players than logistic regression in 88% of cases at draft rate (15%) and convergence threshold (35%). Using individual variables across thresholds, neural networks (specificity = 79 ± 13%, sensitivity = 61 ± 24%, accuracy = 76 ± 8%) were consistently superior to logistic regression (specificity = 73 ± 15%, sensitivity = 29 ± 14%, accuracy = 66 ± 11%). Where the goal is to identify talented players with draft potential, model sensitivity is paramount, and neural networks were superior to logistic regression.

BackgroundChronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course.Objectives1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team.MethodsWe used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework.ResultsEight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, pConclusionsThe "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.

The dynamics and drivers of inter-species interactions in the wild are poorly understood, particularly those involving social animal species. Inter-species interactions between cetaceans and sirenians have rarely been documented and investigated. Here, we report 10 cases of interaction initiated by adult bottlenose dolphins (Tursiops truncatus) towards Antillean manatee (Trichechus manatus manatus). Interactions were documented through behavioral observations in the wild (n = 7) and from the examination of orphaned calves (i.e., tooth rake marks on their body; n = 4) that entered a rehabilitation facility, one individual both observed interacting with dolphins and found stranded with bite marks. Bottlenose dolphins were observed interacting with orphan manatee calves and with mother-calf pairs, exhibiting agonistic behavior (n = 2), affiliative or neutral behaviors (n = 1), but the behavioral contexts of these interactions remain unclear in most cases (n = 7). Information on stranded individuals was collected from four calves (of 13 examined calves) recovered in poor condition with bottlenose dolphin tooth rakes and bite wounds on their bodies, one of which died. Injury from bite wounds varied in extent and severity, ranging from superficial scratches leaving rake marks to deep lacerations. Our findings suggest the regular occurrence of agonistic behaviors initiated by adult bottlenose dolphins and directed toward manatee calves. However, the drivers of these interactions remain unknown and need to be further investigated.

PurposeMetastatic breast cancer [MBC] is the leading cause of cancer death in women globally with no cure. Women diagnosed with MBC endure a catastrophic upheaval to multiple aspects of their life and a radically transformed future landscape. Evidence suggests that the provision of care for women living with metastatic breast cancer is inadequate, socially isolating and stigmatising. To date, this topic has received little research attention. To increase understanding of the experiences of women living with MBC, a synthesis of current evidence is required. This paper presents a review of qualitative evidence on women's experiences of MBC.MethodsA qualitative evidence synthesis [QES] was conducted to synthesise primary qualitative research on the experiences of women living with MBC. Searches were performed of electronic databases Medline, Medline Ovid, PsycINFO, Psych articles, PubMED, CINAHL Complete, Scopus and grey literature databases. The methodological quality of the included studies was appraised using a modified version of the Critical Appraisal Skills Programme [CASP]. Title, abstract, and full-text screening were undertaken. A 'best fit' framework approach using the ARC [Adversity, Restoration, Compatibility] framework was used to guide data extraction and synthesis. Confidence in the findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation, Confidence in the Evidence from Reviews of Qualitative research [GRADE-CERQual].Results28 papers from 21 research studies containing 478 women's experiences of living with MBC were deemed suitable for inclusion in this qualitative evidence synthesis. Findings are presented in a new conceptual framework RAAW [adapted from ARC] for women living with MBC under themes: Reality, Adversity, Adjustment and Wellbeing. Findings revealed that a diagnosis of MBC impacted every aspect of women's lives; this is different to a diagnosis of early breast cancer. An overarching theme of lack of support extended across various facets of their lives. A lack of psychological, emotional, and psychosocial support was evident, with a critical finding that models of care were not fit for purpose. Deficits included a lack of information, knowledge, inclusion in shared decision-making and MDT support, specifically the need for palliative care/oncology support access. Some women living with MBC wanted to be identified as having a chronic illness not a life-limiting illness. Culture and socioeconomic standing influenced the availability of various types of support. The impact of treatment and symptoms had an adverse effect on women's quality of life and affected their ability to adjust.ConclusionThis review synthesised the qualitative literature on the experiences of women living with MBC. The ARC framework used in the synthesis was adapted to develop a revised conceptual framework titled RAAW to represent the evidence from this review on experiences for women living with MBC; Reality & Adversity: A diagnosis of MBC; Adjustment: Living with MBC; Wellbeing: Awareness, meaning, engagement [RAAW; MBC].

When designing phylogeographic investigations researchers can choose to collect many different types of molecular markers, including mitochondrial genes or genomes, SNPs from reduced representation protocols, large sequence capture data sets, and even whole genomes. Given that the statistical power and accuracy of various analyses are expected to differ depending on both the type of marker and the amount of data collected, an exploration of the variance across methodological results as a function of marker type should provide valuable information to researchers. Here we collect mitochondrial Cytochrome b sequences, whole mitochondrial genomes, single nucleotide polymorphisms (SNP)s isolated using a genotype by sequencing (GBS) protocol, sequences from ultraconserved elements, and low-coverage nuclear genomes from the North American water vole (Microtus richardsoni). We estimate genetic distances, population genetic structure, and historical demography using data from each of these datasets and compare the results across markers. As anticipated, the results exhibit differences across marker types, particularly in terms of the resolution offered by different analyses. A cost-benefit analysis indicates that SNPs collected using a GBS protocol are the most cost-effective molecular marker, with inferences that mirror those collected from the whole genome data at a fraction of the cost per sample.

BackgroundIn the short term, parental presence while a human infant is in pain buffers the immediate pain responses, although emerging evidence suggests repeated social buffering of pain may have untoward long-term effects.Methods/findingTo explore the short- and long-term impacts of social buffering of pain, we first measured the infant rat pup's [postnatal day (PN) 8, or 12] response to mild tail shock with the mother present compared to shock alone or no shock. Shock with the mother reduced pain-related behavioral activation and USVs of pups at both ages and reduced Fos expression in the periaqueductal gray, hypothalamic paraventricular nucleus, and the amygdala at PN12 only. At PN12, shock with the mother compared to shock alone differentially regulated expression of several hundred genes related to G-protein-coupled receptors (GPCRs) and neural development, whereas PN8 pups showed a less robust and less coherent expression pattern. In a second set of experiments, pups were exposed to daily repeated Shock-mother pairings (or controls) at PN5-9 or PN10-14 (during and after pain sensitive period, respectively) and long-term outcome assessed in adults. Shock+mother pairing at PN5-9 reduced adult carrageenan-induced thermal hyperalgesia and reduced Fos expression, but PN10-14 pairings had minimal impact. The effect of infant treatment on adult affective behavior showed a complex treatment by age dependent effect. Adult social behavior was decreased following Shock+mother pairings at both PN5-9 and PN10-14, whereas shock alone had no effect. Adult fear responses to a predator odor were decreased only by PN10-14 treatment and the infant Shock alone and Shock+mother did not differ.Conclusions/significanceOverall, integrating these results into our understanding of long-term programming by repeated infant pain experiences, the data suggest that pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone.

Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children ("primary" stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

The aim of this review was to summarise the methods used to predict and assess maturity status and timing in adolescent, male, academy soccer players. A systematic search was conducted on PubMed, Scopus, Web of Science, CINAHL, Medline and SPORTDiscus. Only experimental studies including male, academy players aged U9-U18 years registered with a professional soccer club were included. The methodological quality of the included studies was assessed using guidelines from the Framework of Potential Biases. Fifteen studies fulfilled our inclusion criteria. Studies were mainly conducted in European countries (n = 12). In total, 4,707 players were recruited across all 15 studies, with an age range of 8-18 years. Five studies were longitudinal, two studies were mixed-method designs and eight studies were cross-sectional. Due to high heterogeneity within the studies, a meta-analysis was not performed. Our findings provided no equivalent estimations of adult height, skeletal age, or age at PHV. Discrepancies were evident between actual and predicted adult height and age at PHV. The Bayley-Pinneau [1952], Tanner-Whitehouse 2 [1983] and Khamis-Roche [1994] methods produced estimates of adult height within 1cm of actual adult height. For age at PHV, both Moore [2015] equations produced the closest estimates to actual age at PHV, and the Fransen [2018] equation correlated highly with actual age at PHV (>90%), even when the period between chronological age and age at PHV was large. Medical imaging techniques (e.g., Magnetic Resonance Imaging, X-Ray, Dual energy X-ray Absorptiometry) demonstrated high intra/inter-rater reliability (ICC = 0.83-0.98) for skeletal maturity assessments. The poor concordance between invasive and non-invasive methods, is a warning to practitioners to not use these methods interchangeably for assessing maturational status and timing in academy soccer players. Further research with improved study designs is required to validate these results and improve our understanding of these methods when applied in this target population.

Introduction Little is known about the impact of mandated vaccination policies on the primary care clinic workforce in the United States or differences between rural and urban settings, especially for COVID-19. With the continued pandemic and an anticipated increase in novel disease outbreaks and emerging vaccines, healthcare systems need additional information on how vaccine mandates impact the healthcare workforce to aid in future decision-making. Methods We conducted a cross-sectional survey of Oregon primary care clinic staff between October 28, 2021– November 18, 2021, following implementation of a COVID-19 vaccination mandate for healthcare personnel. The survey consisted of 19 questions that assessed the clinic-level impacts of the vaccination mandate. Outcomes included job loss among staff, receipt of an approved vaccination waiver, new vaccination among staff, and the perceived significance of the policy on clinic staffing. We used univariable descriptive statistics to compare outcomes between rural and urban clinics. The survey also included three open-ended questions that were analyzed using a template analysis approach. Results Staff from 80 clinics across 28 counties completed surveys, representing 38 rural and 42 urban clinics. Clinics reported job loss (46%), use of vaccination waivers (51%), and newly vaccinated staff (60%). Significantly more rural clinics (compared to urban) utilized medical and/or religious vaccination waivers (71% vs 33%, p = 0.04) and reported significant impact on clinic staffing (45% vs 21%, p = 0.048). There was also a non-significant trend toward more job loss for rural compared to urban clinics (53% vs. 41%, p = 0.547). Qualitative analysis highlighted a decline in clinic morale, small but meaningful detriments to patient care, and mixed opinions of the vaccination mandate. Conclusions Oregon’s COVID-19 vaccination mandate increased healthcare personnel vaccination rates, yet amplified staffing challenges with disproportionate impacts in rural areas. Staffing impacts in primary care clinics were greater than reported previously in hospital settings and with other vaccination mandates. Mitigating primary care staffing impacts, particularly in rural areas, will be critical in response to the continued pandemic and novel viruses in the future.

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

The Normalized Difference Vegetation Index (NDVI), derived from reflected visible and infrared radiation, has been critical to understanding change across the Arctic, but relatively few ground truthing efforts have directly linked NDVI to structural and functional properties of Arctic tundra ecosystems. To improve the interpretation of changing NDVI within moist acidic tundra (MAT), a common Arctic ecosystem, we coupled measurements of NDVI, vegetation structure, and CO2 flux in seventy MAT plots, chosen to represent the full range of typical MAT vegetation conditions, over two growing seasons. Light-saturated photosynthesis, ecosystem respiration, and net ecosystem CO2 exchange were well predicted by NDVI, but not by vertically-projected leaf area, our nondestructive proxy for leaf area index (LAI). Further, our data indicate that NDVI in this ecosystem is driven primarily by the biochemical properties of the canopy leaves of the dominant plant functional types, rather than purely the amount of leaf area; NDVI was more strongly correlated with top cover and repeated cover of deciduous shrubs than other plant functional types, a finding supported by our data from separate "monotypic" plots. In these pure stands of a plant functional type, deciduous shrubs exhibited higher NDVI than any other plant functional type. Likewise, leaves from the two most common deciduous shrubs, Betula nana and Salix pulchra, exhibited higher leaf-level NDVI than those from the codominant graminoid, Eriophorum vaginatum. Our findings suggest that recent increases in NDVI in MAT in the North American Arctic are largely driven by expanding deciduous shrub canopies, with substantial implications for MAT ecosystem function, especially net carbon uptake.

BackgroundStudies addressing frailty are limited in the global south, including Ethiopia. We estimated the prevalence of frailty and associated factors among older people living with HIV (PLHIV) attending a large Comprehensive Specialized Hospital in southern Ethiopia.MethodsA systematic sample of 187 PLHIV and 187 HIV-negative controls > 50 years old were recruited between October 1 and November 30, 2021. Data on socio-demographic, behavioural and clinical characteristics were collected using a structured questionnaire. Frailty assessments were completed using the brief frailty instrument (B-FIT-2), which consists of 6 components. Scoring 5-6 points was frail, 2-4 points were pre-frail and below 2 was considered as non-frail. Logistic regression model was used to measure association between variables.ResultsMedian (IQR) age was 53 (50, 80) for PLWH and 59 (55-66) for controls. Prevalence of frailty was 9.1% for PLHIV Versus 5.9% for controls. A significant proportion of PLHIV was pre-frail; 141 (75.4%) compared to controls 110 (58.8%). Pre-frailty status was associated with HIV diagnosis (adjusted odds ratio (aOR) 4.2; 95% CI 1.8-9.9), low age (aOR 0.3; 95% CI 0.1-0.6), lower educational attainment (aOR 2.2; 95% CI 1.0-4.9), being farmer (aOR 3.2; 95% CI 1.0-10.2) and having high or low body mass index (BMI) (aOR 11.3; 95% CI 4.0-25.8). HIV diagnosis (aOR 9.7; 95% CI 1.6-56.8), age (aOR 0.2; 95% CI 0.1-0.7), lower educational attainment (aOR 5.2; 95% CI 1.5-18.2), single status (aOR 4.2; 95% CI 1.3-13.6), farmer (aOR 19.5; 95% CI 3.5-109.1) and high or low BMI (aOR 47.3; 95% CI 13.8-161.9) predicted frailty.ConclusionA high proportion of frailty and pre-frailty was observed in a cohort of older PLHIV attending care in Southern Ethiopia. Future research should focus on interventions targeting factors associated with frailty.