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Students with disabilities continue to experience barriers to accessing tertiary (i.e., postsecondary) education in Australia. Using the principles of Universal Design for Learning (UDL) may help educators proactively address barriers through the design of more accessible and inclusive educational experiences. However, at present, references to UDL appear in only a small number of Australian educational policies and tertiary institute websites, and few tertiary educators use UDL in practice. In this article, we describe how a team of educators, learning designers, accessibility advocates, and people with disabilities from multiple institutions across Australia collaborated to co-create a free, accessible eLearning program to build workforce knowledge and skill in UDL. We first describe how the advisory group was established, how the Knowledge to Action cycle was used to guide the activities of the advisory group, and the evaluation framework that was used to assess the outcomes of the eLearning program. We share potential future activities to raise awareness of UDL and influence policy and practice in local contexts and propose directions for future work in this area.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Reconstructions of palaeoseismicity are useful for understanding and mitigating seismic hazard risks. We apply cosmogenic 36Cl exposure-age dating and measurements of rare-earth elements and yttrium (REE-Y) concentrations to the palaeoseismic history of the Sparta Fault, Greece. Bayesian-inference Markov chain Monte Carlo (MCMC) modelling of 36Cl concentrations along a 7.2 m long vertical profile on the Sparta Fault scarp at Anogia indicate an increase in the average slip rate of the scarp from 0.8–0.9 mm yr−1 6.5–7.7 kyr ago to 1.1–1.2 mm yr−1 up to the devastating 464 BCE earthquake. The average exhumation of the entire scarp up to the present day is 0.7–0.8 mm yr−1. Modelling does not indicate additional exhumation of the Sparta Fault after 464 BCE. The Sparta Fault scarp is composed of fault breccia, containing quartz and clay-lined pores, in addition to host-rock-derived clasts of calcite and microcrystalline calcite cement. The impurities control the distribution of REE-Y in the fault scarp surface and contribute spatial variation to 36Cl concentrations, which precludes the identification of individual earthquakes that have exhumed the Sparta Fault scarp from either of these data sets. REE-Y may illustrate processes that localize slip to a discrete fault plane in the Earth's near-surface, but their potential use in palaeoseismicity would benefit from further evaluation.

Abstract The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.

Abstract Effective approaches are needed to conserve the planet's remaining wildlife and wilderness landscapes, especially concerning global biodiversity conservation targets. Here, we present a new software system called EarthRanger: an open‐source platform built to help monitor, research and manage ecosystems. EarthRanger consists of seven main components (Core Server, API, Storage, Gundi, Web App, Mobile App, Ecoscope) that provide functionality for data (i) aggregation & collection, (ii) storage & management, (iii) real‐time and post hoc analysis, (iv) visualisation and (v) dissemination. The mobile application provides field‐based data recording and visualisation tools. EarthRanger may be deployed for single project use or can aggregate across multiple geographies as a centralised hub. EarthRanger can be used to collect standardised tracking data (e.g. from wildlife collars, vehicles and ranger patrols) and configurable event information (e.g. a singular recording with associated user‐defined attribute information such as a wildlife sighting or encounter with a poacher). Since development began in 2015, the platform has (at the time of writing) been deployed at over 500 sites across 70 countries and with myriad configurations and objectives. EarthRanger has improved the ability to monitor data feeds and manage conservation‐related operations in real time. For instance, the deployment of EarthRanger by African Parks has led to the removal of over 50,000 snares, steady population growth of key species of concern and near cessation of poaching. In Liwonde's protected area, enhanced mitigation efforts supported by EarthRanger reduced the number of deaths from wildlife conflict by more than 91%. EarthRanger is also providing a platform to enhance standardisation, aggregation, transfer and long‐term storage of ecological information and promote collaboration between groups conducting protected area management and ecology and biodiversity research.

Abstract Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of virus gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found in all flaviviruses, we identify the translation of unrecognised upstream open reading frames (uORFs) in the genomic 5′ region. In Asian/American strains, ribosomes translate uORF1 and uORF2, whereas in African strains, the two uORFs are fused into one (African uORF). We use reverse genetics to examine the impact on ZIKV fitness of different uORFs mutant viruses. We find that expression of the African uORF and the Asian/American uORF1 modulates virus growth and tropism in human cortical neurons and cerebral organoids, suggesting a potential role in neurotropism. Although the uORFs are expressed in mosquito cells, we do not see a measurable effect on transmission by the mosquito vector in vivo. The discovery of ZIKV uORFs sheds new light on the infection of the human brain cells by this virus and raises the question of their existence in other neurotropic flaviviruses.

Social Stories (also known as social narratives) help individuals participate in and understand social situations. This scoping review identifies and synthesizes social narrative research targeting behavior change in individuals with ASD. Using the following questions as a guide: (a) What is the scope of social narrative interventions used for individuals with ASD, (b) What behavior change outcome measures are evaluated, and (c) What research designs are used; five databases were searched from 2007-to-2018. Fifty-six articles met the criteria. Primary outcomes were sorted into two macro-categories: Reduce Disruptive Behaviors and Increase Desired Behaviors. Most, but not all, studies were found to be effective for various behaviors such as aggressive actions, verbal protests, identifying emotions, executive functioning, following directions, and responding in social situations. Social narratives can be used to promote skills/behaviors in individuals with ASD to enable participation, an important goal in occupational therapy practice. They are an accessible and feasible intervention that can be implemented in various settings for behaviors including activities of daily living, social skills, independence, and self-regulation. Most research reviewed used a single subject design, which is a limitation of the research as it makes results difficult to generalize. However, through replication, functional relationships can be determined. Additional research utilizing randomized control trials is recommended.

Background The National Institute for Health and Care Excellence (NICE) guideline quality standard for non-ST-segment elevation acute coronary syndrome (NSTEACS) pathway states that adults who have an intermediate or higher risk of future adverse cardiovascular events should undergo coronary angiography within 72 hours of first admission to hospital.The aim was to improve compliance with the 72-hour NICE quality standard for the acute coronary syndrome pathway between one district general hospital (DGH) and its cardiac tertiary centre by reducing the time from admission to angiography by 50%.Participants were front-line staff in the DGH and staff in the cardiac catheter laboratory in the tertiary centre.Methods Continuous data were collected prospectively on all patients entering the NSTEACS pathway with time of arrival to hospital; referral to angiography; and start of angiogram to measure the NSTEACS pathway duration against the NICE quality standard. We used process mapping, ease-benefit matrix, Pareto analyses and the Institute for Healthcare Improvement (IHI) Plan-Do-Study-Act (PDSA) method of quality improvement.Intervention Staff in both hospitals performed process mapping of their respective parts of the NSTEACS pathway. Their data informed decisions on process changes using the ease-benefit matrix. PDSA cycles were commenced, and changes were assessed using continuous measurement of pathway duration. In the tertiary centre, Pareto analysis was performed to help identify the major service constraints.Results Between January 2021 and March 2023, there were four separate PDSA cycles, two each in the DGH and tertiary centre. Across the four PDSA cycles, the time to complete the pathway reduced from an average of 172 to 94.72 hours, an improvement of 45%, along with an overall reduction in variability of data. In the DGH, the process changes were sustained, but in the tertiary centre they were not, as PDSA 4 required staff recruitment to enable a 6-day rather than a 5-day service per week.

Abstract We report here a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine. The polymerization reaction is catalysed by a pincer complex of Earth-abundant metal, manganese, and produces water as the only byproduct. Industrial processes to produce polyethyleneimines involve the transformation of ethanolamine to a highly toxic chemical, aziridine, by an energy-intensive/waste-generating process followed by the ring-opening polymerization of aziridine. The reported method bypasses the need to produce a highly toxic intermediate and presents advantages over the current state-of-the-art. We propose that the polymerization process follows a hydrogen borrowing pathway that involves (a) dehydrogenation of ethanolamine to form 2-aminoacetaldehyde, (b) dehydrative coupling of 2-aminoacetaldehyde with ethanolamine to form an imine derivative, and (c) subsequent hydrogenation of imine derivative to form alkylated amines.

In situ cosmogenic 14C (in situ 14C) in quartz provides a recently developed tool to date exposure of bedrock surfaces of up to ∼ 25 000 years. From outcrops located in east-central Sweden, we tested the accuracy of in situ 14C dating against (i) a relative sea level (RSL) curve constructed from radiocarbon dating of organic material in isolation basins and (ii) the timing of local deglaciation constructed from a clay varve chronology complemented with traditional radiocarbon dating. Five samples of granitoid bedrock were taken along an elevation transect extending southwestwards from the coast of the Baltic Sea near Forsmark. Because these samples derive from bedrock outcrops positioned below the highest postglacial shoreline, they target the timing of progressive landscape emergence above sea level. In contrast, in situ 14C concentrations in an additional five samples taken from granitoid outcrops above the highest postglacial shoreline, located 100 km west of Forsmark, should reflect local deglaciation ages. The 10 in situ 14C measurements provide robust age constraints that, within uncertainties, compare favourably with the RSL curve and the local deglaciation chronology. These data demonstrate the utility of in situ 14C to accurately date ice sheet deglaciation, and durations of postglacial exposure, in regions where cosmogenic 10Be and 26Al routinely return complex exposure results.

Objectives This study explores the influence of clinic-led onboarding and interaction processes on patient engagement within a digital health program for long COVID care, the Living with COVID Recovery (LWCR) program. We compared clinical practices and patient engagement levels across seven clinics utilising LWCR, gaining insights that could optimise digital health interventions (DHIs) for long COVID care. Methods Using a mixed-methods approach, we conducted qualitative interviews with clinicians from seven clinics (out of thirty five) to understand their onboarding and interaction strategies for the LWCR program. We also performed a descriptive quantitative analysis of patient and clinic usage data to rank and classify patient engagement. These rankings were then compared against qualitative insights to explore the influence of clinic-led strategies on patient engagement. Additionally, we conducted interviews with 12 patients under the care of seven clinics to complement our mixed-method analysis. Results Four key practices were identified in clinics with higher patient engagement: pre-assessment onboarding, proactive communication, patient education and the involvement of clinically experienced staff. Clinics that integrated these interdependent practices into a cohesive strategy demonstrated notably higher patient engagement levels. Conclusion This study highlights the critical role of integrating multiple, interdependent clinic-led strategies to optimise patient engagement in DHIs, particularly for long COVID care. These findings provide actionable insights for healthcare providers and policymakers, suggesting that a comprehensive approach is essential for maximising patient engagement and improving care outcomes. The study lays the groundwork for future research to explore the broader applicability of these strategies across different healthcare contexts.

Objectives To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.Design A population-based longitudinal cohort study using real-time user data.Setting 35 specialised long COVID clinics in the UK.Participants 4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.Main outcome measures Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.Results The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was −0.86 (95% CI −1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.Conclusions Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

Summary: Background: Currently, there is no licensed treatment for chronic norovirus infections, but the use of intra-duodenally-delivered immunoglobulins is promising; nevertheless, varying results have limited their wide use. Little is known about the relationship between norovirus genetic diversity and treatment efficacy. Methods: We analyzed the norovirus within-host diversity and evolution in a cohort of 20 immunocompromised individuals using next-generation sequencing (NGS) and clone-based sequencing of the capsid (VP1) gene. Representative VP1s were expressed and their glycan receptor binding affinity and antigenicity were evaluated. Findings: The P2 domain, within the VP1, accumulated up to 30-fold more non-synonymous mutations than other genomic regions. Intra-host virus populations in these patients tended to evolve into divergent lineages that were often antigenically distinct. Several of these viruses were widely resistant to binding-blocking antibodies in immunoglobulin preparations. Notably, for one patient, a single amino-acid substitution in the P2 domain resulted in an immune-escape phenotype, and it was likely the main contributor to treatment failure. Furthermore, we found evidence for transmission of late-stage viruses between two immunocompromised individuals. Interpretation: The findings demonstrated that within-host noroviruses in chronic infections tend to evolve into antigenically distinct subpopulations. This antigenic evolution was likely caused by the remaining low immunity levels exerted by immunocompromised individuals, possibly undermining antiviral treatment. Our observations provide insights into norovirus (within-host) evolution and treatment. Funding: Erasmus MC grant mRACE, the European Union's Horizon 2020 research and innovation program under grant agreement No. 874735 (VEO), and the NWO STEVIN award (Koopmans).

Objective and Approach We analysed the effect on subsequent costs of the setting of the first contact for patients with coronary heart disease in Wales. By categorising health events as proactive or reactive, from the event data source (proactive = primary care (general practice) interactions, elective hospital bed days and outpatient attendances. Reactive = accident and emergency (A&E) attendances and emergency hospital bed days). A standard cost was applied to obtain an annualised cost for each patient. The unit cost for each source was GP £36, bed days £398, outpatient £143, A&E £188. Results We found 42,563 people having CHD events during 2015-2019. Of these, 18,390 had a proactive event as their first event, 23,840 had a reactive event first. The ratio of proactive to reactive events was 1: 3.7 (ratio of costs were £1: £6.30). When the first event was proactive the ratio of events was 1: 0.85 (costs were £1: £1.33). When the first event was reactive the ratio was 1: 4.4 (costs were £1: £33.00). Conclusion and Implications The setting of the first contact appears to be key, with costs reducing by a factor of 14 if the first contact was carried out in a planned environment. Can investment in more active management of a condition reduce overall costs? The work has highlighted the power of using anonymised population-scale linked individual-level data and indicates the health resource reductions possible from improved managed care of patients.

Objective and Approach The Welsh Health Specialised Services Committee wanted to demonstrate how specialised interventions reduced subsequent pressures on the health services. We analysed the variation in the cost of patient pathways for eight cardiac interventions in both planned and emergency settings. A standard cost was allocated to each health event (hospital admissions, general practitioner interactions, outpatient attendances and accident and emergency attendances). A comparison was made for each intervention relating to the condition before the intervention against costs afterwards. In addition, analysis was carried out measuring which patient's characteristics affected the likelihood that patients incurred higher post-intervention costs. Results 10,480 interventions were analysed. In 9 (of the 16) intervention combinations, post-intervention costs dropped. After the implantation of a Cardiac Device, health resource usage dropped by £1,461 per annum. In addition, the likelihood of falling into a higher cost category increased depending on deprivation. For percutaneous coronary intervention (PCI) the odds ratio and 95% confidence interval was 1.34 (1.03 to 1.76) and for Cardiac Devices 2.91 (1 to 15.23). Conclusions and Implications Some interventions in Cardiac realise significant post intervention savings for the health service. Deprivation affects the risk of patients falling into high post-intervention cost categories for PCI and Cardiac Devices. By using anonymised population-scale linked individual-level data, it is possible to highlight interventions that as well as benefiting patients successfully, reduce future health resource usage. This type of analysis can also highlight how deprivation is linked to increased post intervention costs.

Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June-September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences (N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022.

Background: Adolescent loneliness and poor mental health represent dual public health concerns. Yet, associations between loneliness and mental health, and critically, how these associations vary in school settings are less understood. Aims: Framed by social-ecological theory, we aimed to identify key predictors of adolescent mental health and examine school-level variation in the relationship between loneliness and mental health. Sample: Cross-sectional data on adolescents from the 2018 wave of the Health Behaviour in School-aged Children study (HBSC) in Scotland were used (N = 5286). Methods: Mental health was measured as a composite variable containing items assessing nervousness, irritability, sleep difficulties and feeling low. Loneliness was measured via a single item assessing how often adolescents felt 'left out'. Multilevel models were used to identify social-ecological predictors of mental health, associations with loneliness and between-school variation. Results: Loneliness, as well as demographic, social and school factors, was found to be associated with mental health. Mental health varied across schools, with the between-school difference greater among adolescents with high levels of loneliness. Additionally, the negative effect of loneliness on mental health was stronger in schools with lower average mental health scores. Conclusions: The findings suggest that schools can play an important role in shaping adolescent mental health. Our study uniquely identifies that school-based interventions targeting mental health may be especially necessary among lonely adolescents, and programmes aimed at tackling loneliness may be more beneficial in schools with poorer mental health.

Abstract Background The COVID-19 pandemic resulted in major inequalities in infection and disease burden between areas of varying socioeconomic deprivation in many countries, including England. Areas of higher deprivation tend to have a different population structure—generally younger—which can increase viral transmission due to higher contact rates in school-going children and working-age adults. Higher deprivation is also associated with a higher presence of chronic comorbidities, which were convincingly demonstrated to be risk factors for severe COVID-19 disease. These two major factors need to be combined to better understand and quantify their relative importance in the observed COVID-19 inequalities. Methods We used UK Census data on health status and demography stratified by decile of the Index of Multiple Deprivation (IMD), which is a measure of socioeconomic deprivation. We calculated epidemiological impact using an age-stratified COVID-19 transmission model, which incorporated different contact patterns and clinical health profiles by decile. To separate the contribution of each factor, we considered a scenario where the clinical health profile of all deciles was at the level of the least deprived. We also considered the effectiveness of school closures and vaccination of over 65-year-olds in each decile. Results In the modelled epidemics in urban areas, the most deprived decile experienced 9% more infections, 13% more clinical cases, and a 97% larger peak clinical size than the least deprived; we found similar inequalities in rural areas. Twenty-one per cent of clinical cases and 16% of deaths in England observed under the model assumptions would not occur if all deciles experienced the clinical health profile of the least deprived decile. We found that more deaths were prevented in more affluent areas during school closures and vaccination rollouts. Conclusions This study demonstrates that both clinical and demographic factors synergise to generate health inequalities in COVID-19, that improving the clinical health profile of populations would increase health equity, and that some interventions can increase health inequalities.

Abstract Orthohantaviruses infect distinct eulipotyphlan and rodent reservoirs throughout the world; some rodent orthohantaviruses can cause disease in humans. In the United States, a primary rodent reservoir for the human-pathogenic Sin Nombre virus (SNV) is the western deermouse (Peromyscus sonoriensis; formerly included in Peromyscus maniculatus). Deermice (rodents of genus Peromyscus) carry presumably distinct orthohantaviruses but, although deermice of ten species have been recorded in New Mexico, only SNV has been reported in rodents from that state. Using a set of pan-orthohantavirus primers, we discovered a non-SNV orthohantavirus in a brush deermouse (P. boylii), trapped in central New Mexico in 2019. Sequencing enabled the generation of a consensus coding-complete genome sequence, revealing similarity to the known partial sequences of the unclassified “Limestone Canyon virus (LSCV)” in GenBank and aligning with the information in an unpublished study of wild-caught brush deermice trapped in southwestern New Mexico in 2006. Phylogenetic analysis of these combined data revealed geospatial clades and overall identity of “LSCV”, uncovering its association with the classified Montaño virus (MTNV), which is known to infect Aztec and Orizaba deermice in central Mexico. Our work emphasizes the importance of determining coding-complete viral genome sequences as a framework for rigorous virus classification as the basis for epidemiological studies.

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

From 2011-2018, we conducted surveillance in marine mammals along the California coast for influenza A virus (IAV), frequently detecting anti-influenza antibodies and intermittently detecting IAV. In spring 2019, this pattern changed. Despite no change in surveillance intensity, we detected IAV RNA in 10 samples in March and April, mostly in nasal and rectal swabs from northern elephant seals (Mirounga angustirostris). Although virus isolation was unsuccessful, IAV sequenced from one northern elephant seal nasal swab showed close genetic identity with pandemic H1N1 IAV subclade 6B.1A.1 that was concurrently circulating in humans in the 2018/19 influenza season. This represents the first report of human A(H1N1)pdm09 IAV in northern elephant seals since 2010, suggesting IAV continues to spill over from humans to pinnipeds.

BackgroundDue to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine.MethodsIn this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships.ResultsBetween June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement.ConclusionsLocally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

ABSTRACT Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both in vitro and in vivo. YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.

Objective To describe perinatal and maternal outcomes of preterm prelabour rupture of membranes (PPROM) before 23 weeks' gestation in a national cohort.Design Prospective observational study.Setting National population based cohort study with the UK Obstetric Surveillance System (UKOSS), a research infrastructure of all 194 obstetric units in the UK, 1 September 2019 to 28 February 2021.Participants 326 women with singleton and 38 with multiple pregnancies with PPROM between 16+0 and 22+6 weeks+days' gestation.Main outcome measures Perinatal outcomes of live birth, survival to discharge from hospital, and severe morbidity, defined as intraventricular haemorrhage grade 3 or 4, or requiring supplemental oxygen at 36 weeks' postmenstrual age, or both. Maternal outcomes were surgery for removal of the placenta, sepsis, admission to an intensive treatment unit, and death. Clinical data included rates of termination of pregnancy for medical reasons.Results Perinatal outcomes were calculated with all terminations of pregnancy for medical reasons excluded, and a worst-best range was calculated assuming that all terminations for medical reasons and those with missing data would have died (minimum value) or all would be liveborn (maximum value). For singleton pregnancies, the live birth rate was 44% (98/223), range 30-62% (98/326-201/326), perinatal survival to discharge from hospital was 26% (54/207), range 17-53% (54/326-173/326), and 18% (38/207), range 12-48% (38/326-157/326) of babies survived without severe morbidity. The rate of maternal sepsis was 12% (39/326) in singleton and 29% (11/38) in multiple pregnancies (P=0.004). Surgery for removal of the placenta was needed in 20% (65/326) and 16% (6/38) of singleton and twin pregnancies, respectively. Five women became severely unwell with sepsis; two died and another three required care in the intensive treatment unit.Conclusions In this study, 26% of women who had very early PPROM with expectant management had babies that survived to discharge from hospital. Morbidity and mortality rates were high for both mothers and neonates. Maternal sepsis is a considerable risk that needs more research. These data should be used in counselling families with PPROM before 23 weeks' gestation, and currently available guidelines should be updated accordingly.

BackgroundThe shift toward online recruitment methods, accelerated by the COVID-19 pandemic, has brought to the forefront the growing concern of encountering fraudulent participants in health care research. The increasing prevalence of this issue poses a serious threat to the reliability and integrity of research data and subsequent findings. ObjectiveThis study aims to explore the experiences of health care researchers (HCRs) who have encountered fraudulent participants while using online recruitment methods and platforms. The primary objective was to gain insights into how researchers detect and mitigate fraudulent behavior in their work and provide prevention recommendations. MethodsA multimethod sequential design was used for this pilot study, comprising a quantitative arm involving a web-based survey followed by a qualitative arm featuring semistructured interviews. The qualitative description approach framed the qualitative arm of the study. Sample sizes for the quantitative and qualitative arms were based on pragmatic considerations that in part stemmed from encountering fraudulent participants in a concurrent study. Content analysis was used to analyze open-ended survey questions and interview data. ResultsA total of 37 HCRs participated, with 35% (13/37) of them engaging in qualitative interviews. Online platforms such as Facebook, email, Twitter (subsequently rebranded X), and newsletters were the most used methods for recruitment. A total of 84% (31/37) of participants indicated that fraudulent participation occurred in studies that mentioned incentives in their recruitment communications, with 71% (26/37) of HCRs offering physical or electronic gift cards as incentives. Researchers identified several indicators of suspicious behavior, including email surges, discrepancies in contact or personal information, geographical inconsistencies, and suspicious responses to survey questions. HCRs emphasized the need for a comprehensive screening protocol that extends beyond eligibility checks and is seamlessly integrated into the study protocol, grant applications, and research ethics board submissions. ConclusionsThis study sheds light on the intricate and pervasive problem of fraudulent participation in health care research using online recruitment methods. The findings underscore the importance of vigilance and proactivity among HCRs in identifying, preventing, and addressing fraudulent behavior. To effectively tackle this challenge, researchers are encouraged to develop a comprehensive prevention strategy and establish a community of practice, facilitating real-time access to solutions and support and the promotion of ethical research practices. This collaborative approach will enable researchers to effectively address the issue of fraudulent participation, ensuring the conduct of high-quality and ethically sound research in the digital age.

Abstract Introduction Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations. Methods We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma. Participants wore accelerometers for 24-hours/day for seven days. Results Of 124 participants (44 mild, 80 difficult-to-treat), no between-group differences were observed in sleep-window, sleep-time, sleep efficiency or wake time. Sleep-onset time was ~ 40 min later in the difficult-to-treat group (p = 0.019). Discussion Broadly, we observed no difference in accelerometer-derived sleep-metrics between mild and difficult-to-treat asthma. This is the largest analysis of accelerometer-derived sleep parameters in asthma and the first comparing groups by asthma severity. Sleep-onset initiation may be delayed in difficult-to-treat asthma but a dedicated study is needed to confirm.

Introduction Electronic cigarette (e-cigarette) use is gaining popularity among adults. Monitoring e-cigarette-induced respiratory symptoms is crucial for both clinical and regulatory purposes. We systematically reviewed the current literature to understand the prevalence of respiratory symptoms among exclusive e-cigarette users, dual users, and former smokers. Methods Databases searched included PubMed, CINAHL, Cochrane Library, Embase, and Scopus. We included all English-language, empirical quantitative articles that explored the prevalence of e-cigarette-related respiratory symptoms. Random-effects models were utilized in conducting the meta-analyses. The quality of identified studies was evaluated using the NIH Study Quality Assessment Tools. This study is registered with PROSPERO(#CRD42020165973). Results The literature search identified 1240 references. After removing duplicates and screening for eligibility, 168 studies were included in the final review. The majority of included studies reported a wide range of adverse respiratory symptoms. The respiratory symptoms were prevalent among the exclusive e-cigarette users, dual users, and those who switched from combustible cigarettes to e-cigarettes. Further, out of the RCT studies, 5 were rated as good quality, while 3 were rated as fair. Among the observational studies, 24 were rated as good quality, and 9 were rated as fair. The two experimental studies were both rated as fair quality. Conclusions Continued monitoring of respiratory symptoms among e-cigarette users is warranted. Due to the heterogeneity and inconsistencies among studies, which limit result interpretation and highlight the need for studies assessing causal inference, further research using robust study designs is essential. This will provide clinicians with comprehensive knowledge about the potential respiratory risks of e-cigarette use.

The distribution of authorship in the age of machine learning or artificial intelligence (AI) suggests a taxonomic system that places art objects along a spectrum in terms of authorship: from pure human creation, which draws directly from the interior world of affect, emotions and ideas, through to co-evolved works created with tools and collective production and finally to works that are largely devoid of human involvement. Human and machine production can be distinguished in terms of motivation, with human production being driven by consciousness and the processing of subjective experience and machinic production being driven by algorithms and the processing of data. However, the expansion of AI entangles the artist in ever more complex webs of production and dissemination, whereby the boundaries between the work of the artist and the work of the networked technologies are increasingly distributed and obscured. From this perspective, AI-generated works are not solely the products of an independent machinic agency but operate in the middle of the spectrum of authorship between human and machine, as they are the consequences of a highly distributed model of production that sit across the algorithms and the underlying information systems and data that support them and the artists who both contribute and extract value. This highly distributed state further transforms the role of the artist from the creator of objects containing aesthetic and conceptual potential to the translator and curator of such objects.

This paper describes a comprehensive review of academic integrity across course-level learning outcomes for all courses at one institution. The authors developed a taxonomy based on The International Center for Academic Integrity's (ICAI) fundamental values of academic integrity to audit course-level learning outcomes for evidence of academic integrity instruction. Approximately 23% of the 3379 courses examined demonstrated a clear component of academic integrity and instruction varied across Faculties and levels of study. The study provides insights into academic integrity instruction and opportunities for academic institutions to better understand, utilize, and integrate academic integrity instruction into their courses and programs.

Summary: Leakage of mitochondrial or nuclear DNA into the cytosol can occur following viral infections, radiation damage, and some cancers. Here, we present an optimized protocol for isolating and quantifying cytosolic DNA from mammalian cells. We describe steps for collecting cytosolic fractions from cells, extracting DNA using columns, and quantifying extracted DNA using qPCR. This straightforward protocol can be completed in as little as 5 hours, and allows for the identification of the source of DNA.For complete details on the use and execution of this protocol, please refer to Jahun et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.