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A significant fraction of liquid clouds are not captured in existing CloudSat radar-based products because the clouds are masked by surface clutter or have insufficient reflectivities. To account for these missing clouds, we train a random forest regression model to predict cloud optical depth and cloud top effective radius from other CloudSat and CALIPSO observables that do not include the radar reflectivity profile. By assuming a subadiabatic cloud model, we are then able to retrieve a vertical profile of cloud microphysical properties for all liquid-phase oceanic clouds that are detected by CALIPSO's lidar but missed by CloudSat's radar. Daytime estimates of cloud optical depth, cloud top effective radius, and cloud liquid water path are robustly correlated with coincident estimates from the MODIS instrument on board the Aqua satellite. This new algorithm offers a promising path forward for estimating the water contents of thin liquid clouds observed by CloudSat and CALIPSO at night, when MODIS observations that rely upon reflected sunlight are not available.

Abstract Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14–3–3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14–3–3 signaling pathways similar to brain neurons, are abnormal in SIDS. We also studied platelet surface glycoprotein IX (GPIX), a cell adhesion receptor which is physically linked to 14–3–3. In infants dying of SIDS compared to infants dying of known causes, we found significantly higher intra-platelet 5-HT and 14–3–3 and lower platelet surface GPIX. Serum and plasma 5-HT were also elevated in SIDS compared to controls. The presence in SIDS of both platelet and brainstem 5-HT and 14–3–3 abnormalities suggests a global dysregulation of these pathways and the potential for platelets to be used as a model system to study 5-HT and 14–3–3 interactions in SIDS. Platelet and serum biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of SIDS risk in living infants.

A graph \(G\) whose vertex set can be partitioned into a total dominating set and an independent dominating set is called a TI-graph. We give constructions that yield infinite families of graphs that are TI-graphs, as well as constructions that yield infinite families of graphs that are not TI-graphs. We study regular graphs that are TI-graphs. Among other results, we prove that all toroidal graphs are TI-graphs.

Long-lived “bubbles” of wildfire smoke or volcanic aerosol have recently been observed in the stratosphere, co-located with ozone, carbon monoxide, and water vapour anomalies. These bubbles often survive for several weeks, during which time they ascend through vertical distances of 15 km or more. Meteorological analysis data suggest that this aerosol is contained within strong, persistent anticyclonic vortices. Absorption of solar radiation by the aerosol is hypothesised to drive the ascent of the bubbles, but the dynamics of how this heating gives rise to a single-sign anticyclonic vorticity anomaly have thus far been unclear. We present a description of heating-driven stratospheric vortices, based on an axisymmetric balanced model. The simplest version of this model includes a specified localised heating moving upwards at fixed velocity and produces a steadily translating solution with a single-signed anticyclonic vortex co-located with the heating, with corresponding temperature anomalies forming a vertical dipole, matching observations. A more complex version includes the two-way interaction between a heating tracer, representing the aerosol, and the dynamics. An evolving tracer provides heating which drives a secondary circulation, and this in turn transports the tracer. Through this two-way interaction an initial distribution of tracer drives a circulation and forms a self-lofting tracer-filled anticyclonic vortex. Scaling arguments show that upward velocity is proportional to heating magnitude, but the magnitude of peak quasigeostrophic vorticity is O(f) (f is the Coriolis parameter) and independent of the heating magnitude. Estimates of vorticity from observations match our theoretical predictions. We discuss 3-D effects such as vortex stripping and dispersion of tracer outside the vortex by the large-scale flow, which cannot be captured explicitly by the axisymmetric model and are likely to be important in the real atmosphere. The large O(f) vorticity of the fully developed anticyclones explains their observed persistence and their effective confinement of tracers. To further investigate the early stages of formation of tracer-filled vortices, we consider an idealised configuration of a homogeneous tracer layer. A linearised calculation reveals that the upper part of the layer is destabilised due to the decrease in tracer concentrations with height there, which sets up a self-reinforcing effect where upward lofting of tracer results in stronger heating and hence stronger lofting. Small amplitude disturbances form isolated tracer plumes that ascend out of the initial layer, indicative of a self-organisation of the flow. The relevance of these idealised models to formation and persistence of tracer-filled vortices in the real atmosphere is discussed, and it is suggested that a key factor in their formation is the time taken to reach the fully developed stage, which is shorter for strong heating rates.

Abstract Introduction Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. Methods A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. Results A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided “general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. Conclusions The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

This virtual collection is a celebration. It is a celebration of crystallography in Africa, and a celebration of the international crystallography community. It commemorates the founding of the African Crystallographic Association (AfCA), which was accepted as the newest Regional Associate of the International Union of Crystallography (IUCr) in 2023, the year of the 75th anniversary of the first IUCr Congress and General Assembly. The collection contains research articles authored by scientists across the African continent, as well as a selection of articles giving context to crystallography in Africa. These discuss history, collaboration between scientists and between associations, and various educational and outreach initiatives.

BackgroundChildren in rural communities often lack access to subspecialty medical care. Telemedicine has the potential to improve access to these services but its effectiveness has not been rigorously evaluated for paediatric patients with endocrine conditions besides diabetes.IntroductionThe purpose of this study was to assess the association between telemedicine and visit attendance among patients who received care from paediatric endocrinologists at an academic medical centre in northern California between 2009-2017.MethodsWe abstracted demographic data, encounter information and medical diagnoses from the electronic health record for patients ≤18 years of age who attended at least one in-person or telemedicine encounter with a paediatric endocrinologist during the study period. We used a mixed effects logistic regression model - adjusted for age, diagnosis and distance from subspecialty care - to explore the association between telemedicine and visit attendance.ResultsA total of 40,941 encounters from 5083 unique patients were included in the analysis. Patients who scheduled telemedicine visits were predominantly publicly insured (97%) and lived a mean distance of 161 miles from the children's hospital. Telemedicine was associated with a significantly higher odds of visit attendance (odds ratio 2.55, 95% confidence interval 2.15-3.02, p

ImportancePediatric referral centers are increasingly using telemedicine to provide consultations to help care for acutely ill children presenting to rural and community emergency departments (EDs). These pediatric telemedicine consultations may help improve physician decision-making and may reduce the frequency of overtriage and interfacility transfers.ObjectiveTo examine the use of pediatric critical care telemedicine vs telephone consultations associated with risk-adjusted transfer rates of acutely ill children from community and rural EDs.Design, setting, and participantsA cluster-randomized crossover trial was conducted between November 18, 2015, and March 26, 2018. Analyses were conducted from January 19, 2018, to July 23, 2022, 2022. Participants included acutely ill children aged 14 years and younger presenting to a participating ED in 15 rural and community EDs in northern California.InterventionsParticipating EDs were randomized to use telemedicine or telephone for consultations with pediatric critical care physicians according to 1 of 4 unbalanced (3 telemedicine:1 telephone) crossover treatment assignment sequences.Main outcomes and measuresIntention-to-treat, treatment-received, and per-protocol analyses were performed to determine the risk of transfer using mixed effects Poisson regression analyses with random intercepts for presenting EDs to account for hospital-level clustering.ResultsA total of 696 children (392 boys [56.3%]; mean [SD] age, 4.2 [4.6] years) were enrolled. Of the 537 children (77.2%) assigned to telemedicine, 251 (46.7%) received the intervention. In the intention-to-treat analysis, patients assigned to the telemedicine arm were less likely to be transferred compared with patients assigned to the telephone arm after adjusting for patient age, severity of illness, and hospital study period (risk rate [RR], 0.93; 95% CI, 0.88-0.99). The adjusted risk of transfer was significantly lower in the telemedicine arm compared with the telephone arm in both the treatment-received analysis (RR, 0.81; 95% CI, 0.71-0.94) and the per-protocol analysis (RR, 0.79; 95% CI, 0.68-0.92).Conclusions and relevanceIn this randomized trial, the use of telemedicine to conduct consultations for acutely ill children in rural and community EDs resulted in less frequent overall interfacility transfers than consultations done by telephone.Trial registrationClinicalTrials.gov Identifier: NCT02877810.

Access to pediatric emergency care is oftenlacking for children living in rural andunderserved communities. Hospitals in ruralcommunities are generally less preparedto handle pediatric emergencies. Training and resources were provided to community ED providers through a 7-year UC Davis program(TACTICAL).

For patients with diabetes mellitus requiring specialty care, access to routine careis essential for maintaining a high quality of life and avoiding adverse health outcomes. Telemedicine improves access to diabetes specialists and was rapidly adopted during the COVID-19 pandemic

OBJECTIVE: To develop a nurse-to-family telehealth intervention for pediatric inter-facility transfers using the human-centered design approach. METHODS: We conducted the inspiration and ideation phases of a human-centered design process from July 2022 to December 2022. For the inspiration phase, we conducted a qualitative cross-sectional case study design over 3 months. We used thematic analysis with the framework approach of parent and provider interviews. Five team members individually coded transcripts and then met to discuss memos, update a construct summary sheet, and identify emerging themes. The team adapted themes into How Might We statements. For the ideation phase, multidisciplinary stakeholders brainstormed solutions to the How Might We statements in a design workshop. Workshop findings informed the design of a nurse-to-family telehealth intervention, which was iteratively revised over 2 months based on stakeholder feedback sessions. RESULTS: We conducted interviews with nine parents, 11 nurses, and 13 physicians. Four themes emerged supporting the promise of a nurse-to-family telehealth intervention, the need to effectively communicate the intervention purpose, the value of a user-friendly workflow, and the essentiality of ensuring that diverse populations equitably benefit from the intervention. How Might We statements were discussed among 22 total workshop participants. Iterative adaptations were made to the intervention until feedback from workshop participants and 67 other stakeholders supported no further improvements were needed. CONCLUSION: Human-centered design phases facilitated stakeholder engagement in developing a nurse-to-family telehealth intervention. This intervention will be tested in an implementation phase as a feasibility and pilot trial.

Targeted nitric oxide production is relevant for maintaining cellular energy production, protecting against oxidative stress, regulating cell death, and promoting neuroprotection. This study aimed to characterize the putative interaction of nitric-oxide synthase with mitochondrial proteins. The primary finding of this study is that cytochrome c oxidase (CCO) subunit IV (CCOIV) is associated directly with NOS in brain mitochondria when calcium ions are present. The matrix side of CCOIV binds to the N-terminus of NOS, supported by the abrogation of the binding by antibodies towards the N-terminus of NOS. Evidence supporting the interaction between CCOIV and NOS was provided by the coimmunoprecipitation of NOS from detergent-solubilized whole rat brain mitochondria with antibodies to CCOIV and the coimmunoprecipitation of CCOIV from crude brain NOS preparations using antibodies to NOS. The CCOIV domain that interacts with NOS was identified using a series of overlapping peptides derived from the primary sequence of CCOIV. As calcium ions not only activate NOS, but also facilitate the docking of NOS to CCOIV, this study points to a dynamic mechanism of controlling the bioenergetics by calcium changes, thereby adapting bioenergetics to cellular demands.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

Video games and immersive, narrative experiences are often called upon to help students understand difficult scientific concepts, such as sense of scale. However, the development of educational video games requires expertise and, frequently, a sizable budget. Here, we report on the use of an interactive text-style video game, NanoAdventure, to communicate about sense of scale and nanotechnology to the public. NanoAdventure was developed on an open-source, free-to-use platform with simple coding and enhanced with free or low-cost assets. NanoAdventure was launched in three languages (English, Spanish, Chinese) and compared to textbook-style and blog-style control texts in a randomized study. Participants answered questions on their knowledge of nanotechnology and their attitudes toward nanotechnology before and after reading one randomly assigned text (textbook, blog, or NanoAdventure game). Our results demonstrate that interactive fiction is effective in communicating about sense of scale and nanotechnology as well as the relevance of nanotechnology to a general public. NanoAdventure was found to be the most "fun" and easy to read of all text styles by participants in a randomized trial. Here, we make the case for interactive "Choose Your Own Adventure" style games as another effective tool among educational game models for chemistry and science communication.

Introduction: As an organization with a 75-year history of supporting the teaching of psychology, the Society for the Teaching of Psychology (STP), which also operates as Division 2 of the American Psychological Association, has a significant influence on psychology learning and teaching. Statement of the Problem: In this article, four former STP Vice Presidents for Diversity and International Relations explore STP's history through the lenses of diversity, equity/social justice, inclusion, and international relations. Literature Review: The paper explores the relevant history of STP and incorporates scholarship of teaching and learning literature through an international and social justice lens. Teaching Implications: The authors discussed ways to support BIPOC and underrepresented instructors of psychology. Conclusion: STP and teachers of psychology play a pivotal role in changing the cultural, structural, and institutional processes representing ongoing barriers to diversity, equity, and inclusion, and social justice within the organization and the teaching of psychology. Instructors of psychology are well positioned to promote systemic and structural changes and advocate for social justice for Black, Indigenous, and People of Color (BIPOC) and other underrepresented teachers of psychology.

Positive Behavioral Interventions and Supports (PBIS) is an evidence-based framework for promoting positive school climates and improving student social and behavioral outcomes. Yet secondary schools have lagged behind elementary schools in their adoption and implementation of PBIS. The transition from elementary to middle school is marked by a host of developmental and environmental changes that creates a critical window for establishing supportive school environments. We conducted a series of focus groups with middle school students (N = 45) attending PBIS schools to learn about their views and understandings of PBIS, the perceived impact of these programs, the extent to which they were involved in PBIS, and their recommendations for improving their school's program. Although middle school students' understanding of PBIS was often focused on their acknowledgment system, students identified a range of impacts beyond improving student behavior. Students also expressed a desire for more (a) transparent communication between staff and students and (b) opportunities for students to be actively involved in their school's program. We discuss the implications of these findings with respect to increasing the uptake and impact of PBIS in secondary schools.

We present a genome assembly from an individual female Anopheles marshallii (the malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae) from Lopé, Gabon. The genome sequence is 225.7 megabases in span. Most of the assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled. The complete mitochondrial genome was also assembled and is 15.4 kilobases in length.

We present genome assembly from individual female An. coustani (African malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae) from Lopé, Gabon. The genome sequence is 270 megabases in span. Most of the assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled for both species. The complete mitochondrial genome was also assembled and is 15.4 kilobases in length.

BackgroundThe increase in opioid-related overdoses has caused a decrease in average life expectancy, highlighting the need for effective interventions to reduce overdose risk and prevent subsequent overdoses. Peer support specialists (PSSs) offer an appealing strategy to engage overdose survivors and reduce overdose risk, but randomized controlled trials are needed to formalize peer-led interventions and evaluate their effectiveness. ObjectiveThis National Institute on Drug Abuse Clinical Trials Network (CTN) study is a multisite, prospective, pilot randomized (1:1) controlled trial (CTN protocol 0107) that aims to evaluate the effectiveness of an emergency department (ED)–initiated, peer-delivered intervention tailored for opioid overdose survivors (Peer Intervention to Link Overdose survivors to Treatment [PILOT]), compared with treatment as usual (TAU). MethodsThis study evaluates the effectiveness of the 6-month, PSS-led PILOT intervention compared with TAU on the primary outcome of reducing overdose risk behavior 6 months after enrollment. Adults (aged ≥18 years; N=150) with a recent opioid-related overdose were identified and approached in the ED. Participants were screened and enrolled, either in the ED or within 7 days of ED discharge at research offices or in the community and then asked to complete study visits at months 1, 3, 6 (end of intervention), and 7 (follow-up). Participants were enrolled at 3 study sites in the United States: Greenville, South Carolina; Youngstown, Ohio; and Everett, Washington. Participants randomized to the PILOT intervention received a 6-month, PSS-led intervention tailored to each participant’s goals to reduce their overdose risk behavior (eg, overdose harm reduction, housing, medical, and substance use treatment or recovery goals). Participants randomized to TAU received standard-of-care overdose materials, education, and services provided through the participating EDs. This paper describes the study protocol and procedures, explains the design and inclusion and exclusion decisions, and provides details of the peer-led PILOT intervention and supervision of PILOT PSSs. ResultsStudy enrollment opened in December 2021 and was closed in July 2023. A total of 150 participants across 3 sites were enrolled in the study, meeting the proposed sample size for the trial. Primary and secondary analyses are underway and expected to be published in early 2025. ConclusionsThere is an urgent need to better understand the characteristics of overdose survivors presenting to the ED and for rigorous trials evaluating the effectiveness of PSS-led interventions on engaging overdose survivors and reducing overdose risk. Results from this pilot randomized controlled trial will provide a description of the characteristics of overdose survivors presenting to the ED; outline the implementation of PSS services research in ED settings, including PSS implementation of PSS supervision and activity tracking; and inform ED-initiated PSS-led overdose risk reduction interventions and future research to better understand the implementation and efficacy of these interventions. Trial RegistrationClinicalTrials.gov NCT05123027; https://clinicaltrials.gov/study/NCT05123027 International Registered Report Identifier (IRRID)DERR1-10.2196/60277

Summary: Given the resurgence of syphilis, research endeavors to improve current assays for serological diagnosis and management of this disease are a priority. A proteome-scale platform for high-throughput profiling of the humoral response to Treponema pallidum (T. pallidum) proteins during infection could identify antigens suitable to ameliorate the performance and capabilities of treponemal tests for syphilis. Additionally, because infection-induced immunity is partially protective, profiling the response to T. pallidum outer membrane proteins (OMPs) could help select vaccine candidates. Therefore, we developed a pan-proteome array (PPA) based on the Nichols and SS14 strain complete proteomes and used it to define the immunoglobulin M (IgM) and IgG humoral response to T. pallidum proteins in sera collected longitudinally from long-term infected rabbits and from rabbits that were infected, treated, and re-infected. We identified antigens that could facilitate early diagnosis and immunity to a core set of OMP that could explain protection upon reinfection.

The present research aims to select optimal areas for the installation of wind farms in the north-eastern part of Cuba. The research is based on the free software QGIS, Hierarchical Process Analysis, databases of the information of the alternatives and criteria and Geographic Information Systems (GIS), which makes it possible to know the places where these farms will be installed. In addition, experts were consulted to obtain the weights or level of importance of the selected criteria, such as distance to ports, distances to common roads, distances to population centers, to electrical grids and finally the wind speed. As a result, a mathematical conceptual model was obtained for the selection of optimal zones for the installation of wind farms in the eastern north of Cuba, by means of the MCDM and GIS methods, where it was determined that, within the evaluated alternatives of wind farms, Gibara III is the optimal one. These models will allow the development of wind projects in the eastern region of Holguin, and to be able to manage human, financial and material resources.

Background The Inpatient Telehealth Program permits family to remotely communicate with the patient and care team through secure, live video. We aimed to assess the implementation of this program for family engagement from the perspectives of patients, families, and providers. Methods We used a convergent mixed methods design. The quantitative component was a cross-sectional analysis of surveys assessing patient, family, and provider experience. The qualitative component used thematic analysis of patient, family, and provider interviews plus survey free text responses. We performed memo-writing and coding. We developed hypotheses about relationships among categories and identified analytic themes. We used data transformation and narrative discussion to report the integrated findings. Results Surveys from 214 individuals (33 patients, 145 family, 36 providers) were evaluated. Mean (standard deviation) experience ratings (1-poor, 5-best) were 4.0 (1.5) for patients, 4.6 (0.8) for family, and 4.0 (1.4) for providers. We received 134 free text responses and conducted 21 interviews. Three themes emerged: (1) inpatient telehealth enhanced patient and family experience through strengthened relationships and increased support; (2) inpatient telehealth enhanced patient care through improved information sharing and engagement; (3) low awareness of the program limited adoption. Quantitative and qualitative data aligned in that participants perceived inpatient telehealth to be valuable; however, surveys revealed that patients and providers have relatively lower satisfaction with the program. Conclusion Inpatient telehealth for family engagement was perceived to improve family-centeredness of care. Future work is needed to overcome implementation challenges and to increase awareness of this resource among patients and families.

Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Evidence-based medicine (EBM) emerged from McMaster University in the 1980-1990s, which emphasizes the integration of the best research evidence with clinical expertise and patient values. The Health Information Research Unit (HiRU) was created at McMaster University in 1985 to support EBM. Early on, digital health informatics took the form of teaching clinicians how to search MEDLINE with modems and phone lines. Searching and retrieval of published articles were transformed as electronic platforms provided greater access to clinically relevant studies, systematic reviews, and clinical practice guidelines, with PubMed playing a pivotal role. In the early 2000s, the HiRU introduced Clinical Queries—validated search filters derived from the curated, gold-standard, human-appraised Hedges dataset—to enhance the precision of searches, allowing clinicians to hone their queries based on study design, population, and outcomes. Currently, almost 1 million articles are added to PubMed annually. To filter through this volume of heterogenous publications for clinically important articles, the HiRU team and other researchers have been applying classical machine learning, deep learning, and, increasingly, large language models (LLMs). These approaches are built upon the foundation of gold-standard annotated datasets and humans in the loop for active machine learning. In this viewpoint, we explore the evolution of health informatics in supporting evidence search and retrieval processes over the past 25+ years within the HiRU, including the evolving roles of LLMs and responsible artificial intelligence, as we continue to facilitate the dissemination of knowledge, enabling clinicians to integrate the best available evidence into their clinical practice.

Introduction The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort’s parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.Research design and methods Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs.Results The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education.Conclusions This comprehensive profile provides the context for understanding ENDIA’s scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment.Trial registration number ACTRN12613000794707.

The existing literature points towards the presence of robust mitochondrial mechanisms aimed at mitigating protein dyshomeostasis within the organelle. However, the precise molecular composition of these mechanisms remains unclear. Our data show that inorganic polyphosphate (polyP), a polymer well-conserved throughout evolution, is a component of these mechanisms. In mammals, mitochondria exhibit a significant abundance of polyP, and both our research and that of others have already highlighted its potent regulatory effect on bioenergetics. Given the intimate connection between energy metabolism and protein homeostasis, the involvement of polyP in proteostasis has also been demonstrated in several organisms. For example, polyP is a bacterial primordial chaperone, and its role in amyloidogenesis has already been established. Here, using mammalian models, our study reveals that the depletion of mitochondrial polyP leads to increased protein aggregation within the organelle, following stress exposure. Furthermore, mitochondrial polyP is able to bind to proteins, and these proteins differ under control and stress conditions. The depletion of mitochondrial polyP significantly affects the proteome under both control and stress conditions, while also exerting regulatory control over gene expression. Our findings suggest that mitochondrial polyP is a previously unrecognized, and potent component of mitochondrial proteostasis.

Disruptions to the global supply chains of critical raw materials (CRM) have the potential to delay or increase the cost of the renewable energy transition. However, for some CRM, the primary drivers of these supply chain disruptions are likely to be issues related to environmental, social, and governance (ESG) rather than geological scarcity. Herein we combine public geospatial data as mappable proxies for key ESG indicators (e.g., conservation, biodiversity, freshwater, energy, waste, land use, human development, health and safety, and governance) and a global dataset of news events to train and validate three models for predicting “conflict” events (e.g., disputes, protests, violence) that can negatively impact CRM supply chains: (1) a knowledge-driven fuzzy logic model that yields an area under the curve (AUC) for the receiver operating characteristics plot of 0.72 for the entire model; (2) a naïve Bayes model that yields an AUC of 0.81 for the test set; and (3) a deep learning model comprising stacked autoencoders and a feed-forward artificial neural network that yields an AUC of 0.91 for the test set. The high AUC of the deep learning model demonstrates that public geospatial data can accurately predict natural resources conflicts, but we show that machine learning results are biased by proxies for population density and likely underestimate the potential for conflict in remote areas. Knowledge-driven methods are the least impacted by population bias and are used to calculate an ESG rating that is then applied to a global dataset of lithium occurrences as a case study. We demonstrate that giant lithium brine deposits (i.e., >10 Mt Li2O) are restricted to regions with higher spatially situated risks relative to a subset of smaller pegmatite-hosted deposits that yield higher ESG ratings (i.e., lower risk). Our results reveal trade-offs between the sources of lithium, resource size, and spatially situated risks. We suggest that this type of geospatial ESG rating is broadly applicable to other CRM and that mapping spatially situated risks prior to mineral exploration has the potential to improve ESG outcomes and government policies that strengthen supply chains.

Summary: Despite some evidence indicating diverse roles of whirlin in neurons, the functional corollary of whirlin gene function and behavior has not been investigated or broadly characterized. A single nucleotide variant was identified from our recessive ENU-mutagenesis screen at a donor-splice site in whirlin, a protein critical for proper sensorineural hearing function. The mutation (head-bob, hb) led to partial intron-retention causing a frameshift and introducing a premature termination codon. Mutant mice had a head-bobbing phenotype and significant hyperactivity across several phenotyping tests. Lack of complementation of head-bob with whirler mutant mice confirmed the head-bob mutation as functionally distinct with compound mutants having a mild-moderate hearing defect. Utilizing transgenics, we demonstrate rescue of the hyperactive phenotype and combined with the expression profiling data conclude whirlin plays an essential role in activity-related behaviors. These results highlight a pleiotropic role of whirlin within the brain and implicate alternative, central mediated pathways in its function.

Nonalcoholic fatty liver disease (NAFLD) can be ameliorated by calorie restriction, which leads to the suppressed somatotroph axis. Paradoxically, the suppressed somatotroph axis is associated with patients with NAFLD and is correlated with the severity of fibrosis. How the somatotroph axis becomes dysregulated and whether the repressed somatotroph axis impacts liver damage during the progression of NAFLD are unclear. Here, we identify a regulatory branch of the hepatic integrated stress response (ISR), which represses the somatotroph axis in hepatocytes through ATF3, resulting in enhanced cell survival and reduced cell proliferation. In mouse models of NAFLD, the ISR represses the somatotroph axis, leading to reduced apoptosis and inflammation but decreased hepatocyte proliferation and exacerbated fibrosis in the liver. NAD+ repletion reduces the ISR, rescues the dysregulated somatotroph axis, and alleviates NAFLD. These results establish that the hepatic ISR suppresses the somatotroph axis to control cell fate decisions and liver damage in NAFLD.

BACKGROUND: Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (hybrid immunity), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the US population who have been infected, vaccinated, or have hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. METHODS: In this serial cross-sectional study, nationwide blood donor specimens collected during January-December 2021 were tested for anti-spike and anti-nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population and were compared temporally and by demographic factors. RESULTS: Overall, 1 123 855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity changed as follows: seropositivity due to vaccination without previous infection, increase from 3.5% (95% confidence interval, 3.4%-3.7%) to 64.0%, (63.5%-64.5%); seropositivity due to previous infection without vaccination, decrease from 15.6% (15.2%-16.0%) to 11.7% (11.4%-12.0%); and seropositivity due to hybrid immunity, increase from 0.7% (0.6%-0.7%) to 18.9% (18.5%-19.3%). Combined seroprevalence from infection, vaccination, or both increased from 19.8% (19.3%-20.2%) to 94.5% (93.5%-94.0%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by sex. CONCLUSIONS: Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.

The vertical structure of clouds has a profound effect on the global energy budget, the global circulation, and the atmospheric hydrological cycle. The CloudSat and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) missions have taken complementary, colocated observations of cloud vertical structure for over a decade. However, no globally gridded dataset is available to the public for the full length of this unique combined data record. Here we present the 3S-GEOPROF-COMB product (Bertrand et al. 2023, https://doi.org/10.5281/zenodo.8057791), a globally gridded (level 3S) community data product summarizing geometrical profiles (GEOPROF) of hydrometeor occurrence from combined (COMB) CloudSat and CALIPSO data. Our product is calculated from the latest release (R05) of per-orbit (level-2) combined cloud mask profiles. We process a set of cloud cover, vertical cloud fraction, and sampling variables at 2.5, 5, and 10° spatial resolutions and monthly and seasonal temporal resolutions. We address the 2011 reduction in CloudSat data collection with Daylight-Only Operations (DO-Op) mode by subsampling pre-2011 data to mimic DO-Op collection patterns, thereby allowing users to evaluate the impact of the reduced sampling on their analyses. We evaluate our data product against CloudSat-only and CALIPSO-only global-gridded data products as well as four comparable surface-based sites, underscoring the added value of the combined product. Interest in the product is anticipated for the study of cloud processes, cloud–climate interactions, and as a candidate baseline climate data record for comparison to follow-up satellite missions, among other uses.

Abstract Background Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against “gold standard” (GS) methods to study the feasibility of using such methods in clinical trials. Methods Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I 2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves. Results A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5–98.3), but lacked sensitivity (63.5%, 95% CI 51.3–74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies. Conclusions RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.

Abstract Background Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. Method This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. Discussion This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. Trial registration ISRCTN: ISRCTN83877229. Registered on 09.09.2022.

Abstract Background Aged-care programs that are based in First Nations worldviews are believed to translate to improved quality of life for First Nations Elders. First Nations perspectives of health and well-being incorporates social and cultural determinants in addition to traditional Western biomedical approaches. This is exemplified by the Good Spirit Good Life (GSGL) framework, which comprises 12 strength-based factors determined by First Nations Elders as constituting culturally appropriate ageing. Our objective was to conduct a systematic review of existing aged care models of practice to determine the degree of alignment with the GSGL framework. Recommendations of the national Australian Royal Commission into Aged Care Quality and Safety informed this work. Methods We conducted a systematic search of academic and grey literature in the PubMed, Scopus, Ovid Embase, and Informit online databases. Inclusion criteria comprised English language, original research describing the implementation of First Nations culturally appropriate aged care models, published before August 2022. Research that was not focused on First Nations Elders’ perspectives or quality of life was excluded. We subsequently identified, systematically assessed, and thematically analyzed 16 articles. We assessed the quality of included articles using the Aboriginal and Torres Strait Islander Quality Assessment Tool (ATSIQAT), and the Joanna Briggs Institute (JBI) critical appraisal tool for qualitative research. Results Most studies were of medium to high quality, while demonstrating strong alignment with the 12 GSGL factors. Nine of the included studies detailed whole service Models of care while 7 studies described a single program or service element. Thematic analysis of included studies yielded 9 enablers and barriers to implementing models of care. Conclusions Best-practice First Nations aged care requires a decolonizing approach. Programs with strong adherence to the 12 GSGL factors are likely to improve Elders’ quality of life.

Walking with an exoskeleton represents a sophisticated interplay between human physiology and mechanical augmentation, yet understanding of cortical responses in this context remains limited. To address this gap, this study aimed to explore cortical responses during walking with an ankle exoskeleton, examining how these responses evolve with familiarity to the augmentation. Healthy participants without prior exoskeleton experience underwent EEG, EMG, and motion capture analysis while walking with exoskeleton assistance at 1.2m/s. Initially, exoskeleton-assisted walking induced significant biomechanical changes accompanied by corresponding cortical alterations, leading to increased cortical involvement. In addition, after a brief familiarization period, significant increases in alpha band cortical power were observed, indicating decreased cortical engagement. These findings hold significance for elucidating the cortical mechanisms involved in exoskeleton-assisted walking and may contribute to the development of more seamlessly integrated augmentation devices.

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer’s disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

Abstract Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.

During 2013–2017, the mortality rate ratio for rheumatic heart disease among Indigenous versus non-Indigenous persons in Australia was 15.9, reflecting health inequity. Using excess mortality methods, we found that deaths associated with rheumatic heart disease among Indigenous Australians were probably substantially undercounted, affecting accuracy of calculations based solely on Australian Bureau of Statistics data.

BackgroundSurvivorship for those living with primary CNS cancers begins at diagnosis, continues throughout a person's life, and includes caregivers. Opportunities and challenges exist to advance survivorship care for those living with primary CNS cancers that necessitate stakeholder involvement.MethodsIn June 2021, NCI-CONNECT convened a two-day virtual workshop about survivorship care in neuro-oncology. Two expert panels provided key recommendations and five working groups considered critical questions to identify strengths, weaknesses, opportunities, and threats to the advancement of survivorship care and developed recommendations and action items.ResultsThe following action items emanated from the workshop: seek endorsement of meeting report from stakeholder organizations; address barriers in access to survivorship care and provider reimbursement; advance survivorship research through NIH and private grant support; develop a survivorship tool kit for providers, people living with primary CNS cancers and their caregivers; provide accessible educational content for neuro-oncology, neurology, and oncology community providers about survivorship care in neuro-oncology; and establish core competencies for survivorship care for neuro-oncology providers to be included in training and standardized exams.ConclusionsAction items aim to address access and reimbursement barriers, expand patient and provider education, develop core competencies, and support survivorship research through funding and other supports.