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BACKGROUND: Children and young people (CYP) with intellectual and developmental disabilities (IDDs) have significant additional educational needs compared with the general population. In England, the government has established a system of education, health and care plans (EHCPs) to support children with special educational needs and disabilities, but disparities exist between the degree of need and the availability of support. We conducted a prospective UK national cohort study (IMAGINE) of children with rare pathogenic genomic variants, all of which are associated with IDD, to investigate associated neuropsychiatric risk. Subsequently, we obtained information from the UK's National Pupil Database on their educational progress through the state school system. We aimed to identify whether they had received EHCP provision and whether that support was associated with their family's socioeconomic status, region of domicile, ethnicity, sex, primary special educational needs (SEN) type, academic performance and mental health well-being. METHODS: We recruited 2738 CYP from England into the IMAGINE study between 2014 and 2019. The educational histories of the participants (6-28 years old, mean ± standard deviation = 14 ± 4 years, 56% male) were obtained from the Department for Education's National Pupil Database in 2021. Educational data included attainment scores from the Early Year Foundation Stage (<5 years) to key stage 4 (15-16 years). Each family was assigned an index of multiple deprivation (IMD) score based on their home address postcode. Parents or carers rated their child's emotional and behavioural adjustment on the Strengths and Difficulties Questionnaire (SDQ). The association between receiving an EHCP and the child's IMD score, eligibility for free school meals, English region of domicile, ethnicity, sex, primary SEN type, academic attainment and SDQ score was investigated. RESULTS: In this cohort, 78% of participants had received an EHCP. CYP living in the most deprived IMD deciles were substantially less likely to receive EHCP support than those in the least deprived decile, irrespective of their degree of intellectual developmental disability, academic performance or associated mental health problems. There were no sex differences. Children of Asian heritage were more likely to have been granted an EHCP than White children from equivalent IMD deciles. There were striking regional disparities. Participants living in London were significantly more likely to have been awarded an EHCP than participants living anywhere else in England, regardless of their IMD decile; those in the least deprived decile had almost 100% EHCP provision. CONCLUSIONS: This study found evidence for nationwide regional inconsistencies in the awarding of EHCP to CYP with significant intellectual impairments of known genetic aetiology. Disparities in funds available to education authorities could be a contributory factor. EHCP support was potentially influenced by how strongly a parent advocates for their child.
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We explore the nonlinear interactions of an optomechanical microresonator driven by two external optical signals. Optical whispering-gallery waves are coupled to acoustic surface waves of a fused silica medium in the equatorial plane of a generic microresonator. The system exhibits coexisting attractors whose behaviors include limit cycles, steady states, tori, quasi-chaos, and fully developed chaos with ghost orbits of a known attractor. Bifurcation diagrams demonstrate the existence of self-similarity, periodic windows, and coexisting attractors and show high-density lines within chaos that suggests a potential ghost orbit. In addition, the Lyapunov spectral components as a function of control parameter illuminate the dynamic nature of attractors and periodic windows with symmetric and asymmetric formations, their domains of existence, their bifurcations, and other nonlinear effects. We show that the power-shift method can access accurately and efficiently attractors in the optomechanical system as it does in other nonlinear systems. To test whether the ghost orbit is the link between two attractors interrupted by chaos, we examine the elements of the bifurcation diagrams as a function of control parameter. We also use detuning as a second control parameter to avoid the chaotic region and clarify that the two attractors are one.
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A 10-month-old female neutered domestic shorthair cat presented with a history of urinary incontinence and recurrent bacterial cystitis since 2 months of age. Physical examination was unremarkable other than vulval hypoplasia. Genitourinary dysplasia was diagnosed following a physical examination, CT imaging and retrograde positive contrast urethrocystography. Attempted medical management of the urinary incontinence was unsuccessful. Surgical treatment consisted of cystourethroplasty combined with artificial urethral sphincter placement, resulting in marked improvement of urinary continence. Following multiple adjustments of the artificial urethral sphincter near-total continence was achieved, which was maintained at 10 months post-surgery.
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Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Electroencefalografía , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Enfermedad de Alzheimer/fisiopatología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico , Electroencefalografía/métodos , AncianoRESUMEN
BACKGROUND: Virtual care in Canada rapidly expanded during the COVID-19 pandemic in a low-rules environment in response to pressing needs for ongoing access to care amid public health restrictions. Emergency medicine specialists now face the challenge of advising on which virtual urgent care services ought to remain as part of comprehensive emergency care. Consideration must be given to safe, quality, and appropriate care as well as issues of equitable access, public demand, and sustainability (financial and otherwise). The aim of this project was to summarize current literature and expert opinion and formulate recommendations on the path forward for virtual care in emergency medicine. METHODS: We formed a working group of emergency medicine physicians from across Canada working in a variety of practice settings. The virtual care working group conducted a scoping review of the literature and met monthly to discuss themes and develop recommendations. The final recommendations were circulated to stakeholders for input and subsequently presented at the 2023 Canadian Association of Emergency Physicians (CAEP) Academic Symposium for discussion, feedback, and refinement. RESULTS: The working group developed and reached unanimity on nine recommendations addressing the themes of system design, equity and accessibility, quality and patient safety, education and curriculum, financial models, and sustainability of virtual urgent care services in Canada. CONCLUSION: Virtual urgent care has become an established service in the Canadian health care system. Emergency medicine specialists are uniquely suited to provide leadership and guidance on the optimal delivery of these services to enhance and complement emergency care in Canada.
RéSUMé: CONTEXTE: Les soins virtuels au Canada ont rapidement pris de l'ampleur pendant la pandémie de COVID-19 dans un environnement où les règles sont peu strictes, en réponse aux besoins urgents d'accès continu aux soins dans un contexte de restrictions en santé publique. Les spécialistes de la médecine d'urgence sont maintenant confrontés au défi de conseiller sur les services de soins d'urgence virtuels qui devraient rester dans le cadre des soins d'urgence complets. Il faut tenir compte des soins sécuritaires, de qualité et appropriés, ainsi que des questions d'accès équitable, de la demande publique et de la durabilité (financière et autre). L'objectif de ce projet était de résumer la littérature actuelle et l'opinion d'experts et de formuler des recommandations sur la voie à suivre pour les soins virtuels en médecine d'urgence. MéTHODES: Nous avons formé un groupe de travail composé de médecins urgentistes de partout au Canada qui travaillent dans divers milieux de pratique. Le groupe de travail sur les soins virtuels a effectué un examen de la portée de la documentation et s'est réuni chaque mois pour discuter des thèmes et formuler des recommandations. Les recommandations finales ont été distribuées aux intervenants pour obtenir leurs commentaires, puis présentées au symposium universitaire 2023 de l'Association canadienne des médecins d'urgence (ACMU) pour discussion, rétroaction et perfectionnement. RéSULTATS: Le groupe de travail a élaboré et atteint l'unanimité sur neuf recommandations portant sur les thèmes de la conception du système, de l'équité et de l'accessibilité, de la qualité et de la sécurité des patients, de l'éducation et des programmes, des modèles financiers et de la viabilité des services virtuels de soins d'urgence au Canada. CONCLUSION : Les soins d'urgence virtuels sont devenus un service établi dans le système de santé canadien. Les spécialistes en médecine d'urgence sont particulièrement bien placés pour fournir un leadership et des conseils sur la prestation optimale de ces services afin d'améliorer et de compléter les soins d'urgence au Canada.
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COVID-19 , Medicina de Emergencia , Humanos , COVID-19/epidemiología , Medicina de Emergencia/organización & administración , Canadá , Pandemias , Telemedicina , SARS-CoV-2 , Atención Ambulatoria/organización & administración , Accesibilidad a los Servicios de SaludRESUMEN
findings are presented from an investigation to improve understanding of the environmental risks associated with developing an unconventional-hydrocarbons industry in the UK. The EQUIPT4RISK project, funded by UK Research Councils, focused on investigations around Preston New Road (PNR), Fylde, Lancashire, and Kirby Misperton Site A (KMA), North Yorkshire, where operator licences to explore for shale gas by hydraulic fracturing (HF) were issued in 2016, although exploration only took place at PNR. EQUIPT4RISK considered atmospheric (greenhouse gases, air quality), water (groundwater quality) and solid-earth (seismicity) compartments to characterise and model local conditions and environmental responses to HF activities. Risk assessment was based on the source-pathway-receptor approach. Baseline monitoring of air around the two sites characterised the variability with meteorological conditions, and isotopic signatures were able to discriminate biogenic methane (cattle) from thermogenic (natural-gas) sources. Monitoring of a post-HF nitrogen-lift (well-cleaning) operation at PNR detected the release of atmospheric emissions of methane (4.2 ± 1.4 t CH4). Groundwater monitoring around KMA identified high baseline methane concentrations and detected ethane and propane at some locations. Dissolved methane was inferred from stable-isotopic evidence as overwhelmingly of biogenic origin. Groundwater-quality monitoring around PNR found no evidence of HF-induced impacts. Two approaches for modelling induced seismicity and associated seismic risk were developed using observations of seismicity and operational parameters from PNR in 2018 and 2019. Novel methodologies developed for monitoring include use of machine learning to identify fugitive atmospheric methane, Bayesian statistics to assess changes to groundwater quality, a seismicity forecasting model seeded by the HF-fluid injection rate and high-resolution monitoring of soil-gas methane. The project developed a risk-assessment framework, aligned with ISO 31000 risk-management principles, to assess the theoretical combined and cumulative environmental risks from operations over time. This demonstrated the spatial and temporal evolution of risk profiles: seismic and atmospheric impacts from the shale-gas operations are modelled to be localised and short-lived, while risk to groundwater quality is longer-term.
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Medical datasets inherently contain errors from subjective or inaccurate test results, or from confounding biological complexities. It is difficult for medical experts to detect these elusive errors manually, due to lack of contextual information, limiting data privacy regulations, and the sheer scale of data to be reviewed. Current methods for training robust artificial intelligence (AI) models on data containing mislabeled examples generally fall into one of several categories-attempting to improve the robustness of the model architecture, the regularization techniques used, the loss function used during training, or selecting a subset of data that contains cleaner labels. This last category requires the ability to efficiently detect errors either prior to or during training, either relabeling them or removing them completely. More recent progress in error detection has focused on using multi-network learning to minimize deleterious effects of errors on training, however, using many neural networks to reach a consensus on which data should be removed can be computationally intensive and inefficient. In this work, a deep-learning based algorithm was used in conjunction with a label-clustering approach to automate error detection. For dataset with synthetic label flips added, these errors were identified with an accuracy of up to 85%, while requiring up to 93% less computing resources to complete compared to a previous model consensus approach developed previously. The resulting trained AI models exhibited greater training stability and up to a 45% improvement in accuracy, from 69 to over 99% compared to the consensus approach, at least 10% improvement on using noise-robust loss functions in a binary classification problem, and a 51% improvement for multi-class classification. These results indicate that practical, automated a priori detection of errors in medical data is possible, without human oversight.
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Inteligencia Artificial , Aprendizaje Profundo , Humanos , Algoritmos , Análisis por Conglomerados , ConsensoRESUMEN
We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.
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A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.
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Fracturas de Cadera , Osteoporosis , Fracturas Osteoporóticas , Masculino , Humanos , Femenino , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/complicaciones , Osteoporosis/complicaciones , Fracturas de Cadera/etiología , Fracturas de Cadera/complicaciones , Densidad Ósea , Factores de Riesgo , Medición de RiesgoRESUMEN
OBJECTIVES: We determined the age and sociodemographic distribution of COVID-19 cases between January and September 2020 to identify the group with the highest incidence rates at the beginning of the second wave in England. STUDY DESIGN: We undertook a retrospective cohort study design. METHODS: SARS-CoV-2 cases in England were linked with area-level socio-economic status indicators using quintiles of the Index of Multiple Deprivation (IMD). Age-specific incidence rates were stratified by IMD quintile to further assess rates by area-level socio-economic status. RESULTS: Between July and September 2020, SARS-CoV-2 incidence rates were highest amongst those aged 18-21 years, reaching rates of 213.9 (18-19 years) and 143.2 (20-21 years) per 100,000 population by week ending 21 September 2022. Stratification of incidence rates by IMD quintile evidenced that despite high rates observed in the most deprived areas of England amongst the very young and older age groups, the highest rates were observed in the most affluent areas of England amongst the 18- to 21-year-olds. CONCLUSIONS: The reversal of sociodemographic trend in COVID-19 cases in England for those aged 18-21 years at the end of the summer of 2020 and beginning of the second wave showed a novel pattern of COVID-19 risk. For other age groups, the rates remained highest for those from more deprived areas, which highlighted persisting inequalities. Combined, this demonstrates the need to reinforce awareness of COVID-19 risk for young people, particularly given the late inclusion of the 16-17 years age group for vaccination administration, as well as continued efforts to reduce the impact of COVID-19 on vulnerable populations.
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COVID-19 , Humanos , Anciano , Adolescente , Estudios Retrospectivos , COVID-19/epidemiología , SARS-CoV-2 , Clase Social , Inglaterra/epidemiologíaRESUMEN
Endocrine disrupting chemicals are widely distributed in our environment. Humans are exposed to these compounds not only through their occupations, but also through dietary consumption and exposure to contaminated water, personal care products and textiles. Chemicals that are persistent in the body and in our environment include dioxins and polychlorinated biphenyls. Non-persistent chemicals including bisphenol A, phthalates and parabens are equally as important because they are ubiquitous in our environment. Heavy metals, including lead and cadmium, can also have endocrine disrupting properties. Although difficult to study due to their variety of sources of exposures and mechanisms of action, these chemicals have been associated with early menopause, increased frequency of vasomotor symptoms, altered steroid hormone levels and markers of diminished ovarian reserve. Understanding the impacts of these exposures is important given the potential for epigenetic modification, which can alter gene function and result in multi-generational effects. This review summarizes findings in humans and animals or cell-based models from the past decade of research. Continued research is needed to assess the effects of mixtures of chemicals, chronic exposures and new compounds that are continuously being developed as replacements for toxic chemicals that are being phased out.
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Disruptores Endocrinos , Exposición a Riesgos Ambientales , Humanos , Animales , Femenino , Exposición a Riesgos Ambientales/efectos adversos , Disruptores Endocrinos/toxicidad , MenopausiaRESUMEN
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus is thought to have originated in wild bats from Asia, and as the resulting pandemic continues into its third year, concerns have been raised that the virus will expand its host range and infect North American wildlife species, including bats. Mexican free-tailed bats (Tadarida brasiliensis) live in large colonies in the southern United States, often in urban areas and, as such, could be exposed to the virus from infected humans. We experimentally challenged wild T. brasiliensis with SARS-CoV-2 to determine the susceptibility, reservoir potential, and population impacts of infection in this species. Of 10 bats oronasally inoculated with SARS-CoV-2, 5 became infected and orally excreted moderate amounts of virus for up to 18 days postinoculation. These five subjects all seroconverted and cleared the virus before the end of the study with no obvious clinical signs of disease. We additionally found no evidence of viral transmission to uninoculated subjects. These results indicate that while T. brasiliensis are susceptible to SARS-CoV-2 infection, infection of wild populations of T. brasiliensis would not likely cause mortality. However, the transmission of SARS-CoV-2 from T. brasiliensis to or from humans, or to other animal species, is a possibility requiring further investigation to better define. IMPORTANCE As the COVID-19 pandemic has continued for 3+ years, there has been increasing concern that the SARS-CoV-2 virus will enter wildlife populations and potentially create new reservoirs where the virus could adapt to a new host and create variants. This is particularly possible with species that reside in man-made structures, in proximity to infected human populations. Mexican free-tailed bats (Tadarida brasiliensis) live in large colonies, often in urban settings and, thus, can be exposed by infected humans and potentially transmit the virus to new hosts. We experimentally challenged T. brasiliensis with SARS-CoV-2 and revealed that they are susceptible to the virus and excrete moderate amounts for up to 18 days postinoculation. This is important information for wildlife biologists, wildlife rehabilitation workers, and the general public that may contact these animals.
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COVID-19 , Quirópteros , Animales , Humanos , SARS-CoV-2 , Pandemias , Animales SalvajesRESUMEN
Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.
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Esquizofrenia , Adulto Joven , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Predisposición Genética a la Enfermedad/genética , Encéfalo/diagnóstico por imagen , Factores de Riesgo , GenotipoRESUMEN
Objective: To assess onset of effect in three placebo- or nonsteroidal anti-inflammatory drug (NSAID)-controlled trials of tanezumab in patients with moderate-to-severe osteoarthritis. Methods: Post-hoc nonparametric Kaplan-Meier analyses were used to estimate median time to first improvement and to sustained improvement in Western Ontario and McMaster Universities Osteoarthritis Index domain (Pain, Physical Function, Stiffness) scores across a range of improvement thresholds (0-100%, in 5% increments). Time to first improvement was defined as the first week scores met the pre-specified threshold. Time to sustained improvement was defined as the first week scores met the pre-specified threshold and were sustained (on average) for the remainder of the treatment period. Results: Across all domains, tanezumab-treated patients had shorter median times to first improvement (at most thresholds) and reached higher levels of improvement than placebo-treated patients. No substantial differences were observed between tanezumab doses (2.5 and 5 âmg), or between tanezumab and NSAIDs. Most patients experiencing an event of first improvement went on to experience a sustained event. At low thresholds, sustained improvement occurred simultaneously with, or shortly after, first improvement. At higher thresholds, median time to sustained improvement was longer than median time to first improvement. Conclusions: Following initiation of tanezumab treatment, first improvement of osteoarthritis symptoms of 30% was evident within 2-4 weeks and sustained improvement was evident within 2-8 weeks. Time to improvement of 50% was more variable, with first and sustained events expected within 4-16 and 8-24 weeks, respectively. ClinicalTrialsgov identifiers: NCT02697773; NCT02709486; NCT02528188.
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To determine the safety of using argon as a deuteron beam stopping material, the 40Ar(d,p)41Ar cross section was measured at average deuteron energies of 3.6 MeV, 5.5 MeV, and 7.0 MeV using an activation method. A 16-MeV deuteron beam produced by Lawrence Berkeley National Laboratory's 88-Inch Cyclotron was degraded to each energy by nickel foils and the front wall of an aluminum gas chamber. The reduced-energy deuterons were used to activate a sample of natAr gas. After each irradiation, the gas chamber's 41Ar activation was measured with a high-purity germanium detector. The cross sections measured were larger than a previous measurement by â¼40%.
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CiclotronesRESUMEN
OBJECTIVE: To determine whether household contacts of confirmed cases of COVID-19 have an increased risk of hospitalisation or death. METHODS: We used the HOSTED data set of index cases of COVID-19 in England between June and November 2020, linked to Secondary Uses Service data on hospital episodes and Office for National Statistics' mortality data. Multivariable logistic regression models of the odds of household contacts being hospitalised or dying within six weeks of an index case, adjusted for case type, age, sex and calendar month were calculated. Excess risk was determined by comparing the first six weeks after the index case with 6-12 weeks after the index case in a survival analysis framework. RESULTS: Index cases were more likely to be hospitalised or die than either secondary cases or non-cases, having adjusted for age and sex. There was an increased risk of hospitalisation for non-cases (adjusted hazard ratio (aHR) 1.10; 95% confidence interval (CI) 1.04, 1.16) and of death (aHR 1.57; 95% CI 1.14, 2.16) in the first six weeks after an index case, compared to 6-12 weeks after. CONCLUSION: Risks of hospitalisation and mortality are predictably higher in cases compared to non-cases. The short-term increase in risks for non-case contacts following diagnosis of the index case may suggest incomplete case ascertainment among contacts, although this was relatively small.
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COVID-19 , Composición Familiar , Hospitalización , Humanos , Modelos Logísticos , SARS-CoV-2RESUMEN
The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.
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Adenosine triphosphate (ATP) released from injured or dying cells is a potent pro-inflammatory "danger" signal. Alkaline phosphatase (AP), an endogenous enzyme that de-phosphorylates extracellular ATP, likely plays an anti-inflammatory role in immune responses. We hypothesized that ilofotase alfa, a human recombinant AP, protects kidneys from ischemia-reperfusion injury (IRI), a model of acute kidney injury (AKI), by metabolizing extracellular ATP to adenosine, which is known to activate adenosine receptors. Ilofotase alfa (iv) with or without ZM241,385 (sc), a selective adenosine A2A receptor (A2AR) antagonist, was administered 1 h before bilateral IRI in WT, A2AR KO (Adora2a-/- ) or CD73-/- mice. In additional studies recombinant alkaline phosphatase was given after IRI. In an AKI-on-chronic kidney disease (CKD) ischemic rat model, ilofotase alfa was given after the three instances of IRI and rats were followed for 56 days. Ilofotase alfa in a dose dependent manner decreased IRI in WT mice, an effect prevented by ZM241,385 and partially prevented in Adora2a-/- mice. Enzymatically inactive ilofotase alfa was not protective. Ilofotase alfa rescued CD73-/- mice, which lack a 5'-ectonucleotidase that dephosphorylates AMP to adenosine; ZM241,385 inhibited that protection. In both rats and mice ilofotase alfa ameliorated IRI when administered after injury, thus providing relevance for therapeutic dosing of ilofotase alfa following established AKI. In an AKI-on-CKD ischemic rat model, ilofotase alfa given after the third instance of IRI reduced injury. These results suggest that ilofotase alfa promotes production of adenosine from liberated ATP in injured kidney tissue, thereby amplifying endogenous mechanisms that can reverse tissue injury, in part through A2AR-and non-A2AR-dependent signaling pathways.
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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus originated in wild bats from Asia, and as the resulting pandemic continues into its third year, concerns have been raised that the virus will expand its host range and infect North American wildlife species, including bats. Mexican free-tailed bats ( Tadarida brasiliensis : TABR) live in large colonies in the southern United States, often in urban areas, and as such, could be exposed to the virus from infected humans. We experimentally challenged wild TABR with SARS-CoV-2 to determine the susceptibility, reservoir potential, and population impacts of infection in this species. Of nine bats oronasally inoculated with SARS-CoV-2, five became infected and orally excreted moderate amounts of virus for up to 18 days post inoculation. These five subjects all seroconverted and cleared the virus before the end of the study with no obvious clinical signs of disease. We additionally found no evidence of viral transmission to uninoculated subjects. These results indicate that while TABR are susceptible to SARS-CoV-2 infection, infection of wild populations of TABR would not likely cause mortality. However, the transmission of SARS-CoV-2 from TABR to or from humans, or to other animal species, is a distinct possibility requiring further investigation to better define.