Risk for rabies transmission from encounters with bats, Colorado, 1977-1996.

To assess the risk for rabies transmission to humans by bats, we analyzed the prevalence of rabies in bats that encountered humans from 1977 to 1996 and characterized the bat-human encounters. Rabies was diagnosed in 685 (15%) of 4,470 bats tested. The prevalence of rabies in bats that bit humans was 2.1 times higher than in bats that did not bite humans. At least a third of the encounters were preventable

Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19 : observational cohort study

Background Measurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19. Methods We undertook an observational cohort study across 70 emergency departments during first wave of the COVID-19 pandemic in the United Kingdom. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. Results We analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% confidence interval 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were respectively 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019). Conclusions Post-exertion oxygen saturation provides modest prognostic information in the assessment of patients attending the emergency department with suspected COVID-19

Characterisation of 22446 patients attending UK emergency departments with suspected COVID-19 infection : observational cohort study

Background Hospital emergency departments play a crucial role in the initial management of suspected COVID-19 infection. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. Methods We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22446 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Results Adults were acutely unwell (median NEWS2 score 4) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.9%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Adult men and women presented in similar numbers (10210 versus 10506), but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.7% v 13.3%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to be admitted (60.8%, 57.3%, 69.6%) or die (11.9%, 11.2%, 16.8%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with confirmed COVID-19 had similar age and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.7% v 15.9%). Conclusions Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. People with confirmed COVID-19 have a poor prognosis, compared with similar emergency admissions without confirmed COVID-19

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Oral steroids for hearing loss associated with otitis media with effusion in children aged 2–8 years: the OSTRICH RCT

Background Children with hearing loss associated with otitis media with effusion (OME) are commonly managed through surgical intervention, hearing aids or watchful waiting. A safe, inexpensive, effective medical treatment would enhance treatment options. Small, poorly conducted trials have found a short-term benefit from oral steroids. Objective To determine the clinical effectiveness and cost-effectiveness of a 7-day course of oral steroids in improving hearing at 5 weeks in children with persistent OME symptoms and current bilateral OME and hearing loss demonstrated by audiometry. Design Double-blind, individually randomised, placebo-controlled trial. Setting Ear, nose and throat outpatient or paediatric audiology and audiovestibular medicine clinics in Wales and England. Participants Children aged 2–8 years, with symptoms of hearing loss attributable to OME for at least 3 months, a diagnosis of bilateral OME made on the day of recruitment and audiometry-confirmed hearing loss. Interventions A 7-day course of oral soluble prednisolone, as a single daily dose of 20 mg for children aged 2–5 years or 30 mg for 6- to 8-year-olds, or matched placebo. Main outcome measures Acceptable hearing at 5 weeks from randomisation. Secondary outcomes comprised acceptable hearing at 6 and 12 months, tympanometry, otoscopic findings, health-care consultations related to OME and other resource use, proportion of children who had ventilation tube (grommet) surgery at 6 and 12 months, adverse effects, symptoms, functional health status, health-related quality of life, short- and longer-term cost-effectiveness. Results A total of 389 children were randomised. Satisfactory hearing at 5 weeks was achieved by 39.9% and 32.8% in the oral steroid and placebo groups, respectively (absolute difference of 7.1%, 95% confidence interval –2.8% to 16.8%; number needed to treat = 14). This difference was not statistically significant. The secondary outcomes were consistent with the picture of a small or no benefit, and we found no subgroups that achieved a meaningful benefit from oral steroids. The economic analysis showed that treatment with oral steroids was more expensive and accrued fewer quality-adjusted life-years than treatment as usual. However, the differences were small and not statistically significant, and the sensitivity analyses demonstrated large variation in the results. Conclusions OME in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. Discussions about watchful waiting and other interventions will be enhanced by this evidence. The findings of this study suggest that any benefit from a short course of oral steroids for OME is likely to be small and of questionable clinical significance, and that the treatment is unlikely to be cost-effective and, therefore, their use cannot be recommended

Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial

Background Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80% of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. It has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow up period, or of too poor quality to give a definite answer. The aim of the OSTRICH trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. Methods/Design 380 participants (children aged 2-8 years) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms attributable to OME for at least 3 months and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for one week. Outcomes include audiometry, tympanometry and otoscopy assessments, symptoms, adverse effects, functional health status, quality of life, resource use and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. Discussion There is an important evidence gap regarding clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, non-surgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS

Epstein-Barr Virus Evades CD4+ T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2

Evasion of immune T cell responses is crucial for viruses to establish persistence in the infected host. Immune evasion mechanisms of Epstein-Barr virus (EBV) in the context of MHC-I antigen presentation have been well studied. In contrast, viral interference with MHC-II antigen presentation is less well understood, not only for EBV but also for other persistent viruses. Here we show that the EBV encoded BZLF1 can interfere with recognition by immune CD4+ effector T cells. This impaired T cell recognition occurred in the absence of a reduction in the expression of surface MHC-II, but correlated with a marked downregulation of surface CD74 on the target cells. Furthermore, impaired CD4+ T cell recognition was also observed with target cells where CD74 expression was downregulated by shRNA-mediated inhibition. BZLF1 downregulated surface CD74 via a post-transcriptional mechanism distinct from its previously reported effect on the CIITA promoter. In addition to being a chaperone for MHC-II αβ dimers, CD74 also functions as a surface receptor for macrophage Migration Inhibitory Factor and enhances cell survival through transcriptional upregulation of Bcl-2 family members. The immune-evasion function of BZLF1 therefore comes at a cost of induced toxicity. However, during EBV lytic cycle induced by BZLF1 expression, this toxicity can be overcome by expression of the vBcl-2, BHRF1, at an early stage of lytic infection. We conclude that by inhibiting apoptosis, the vBcl-2 not only maintains cell viability to allow sufficient time for synthesis and accumulation of infectious virus progeny, but also enables BZLF1 to effect its immune evasion function

Hard exercise, affect lability, and personality among individuals with bulimia nervosa

The current study explores the personality traits of compulsivity (e.g., sense of orderliness and duty to perform tasks completely) and restricted expression (e.g., emotion expression difficulties) as potential moderators of the relation between affect lability and frequency of hard exercise episodes in a sample of individuals with bulimic pathology. Participants were 204 adult females recruited in five Midwestern cities who met criteria for threshold or subthreshold bulimia nervosa (BN). Compulsivity was found to significantly moderate the relation between affect lability and number of hard exercise episodes over the past 28 days, such that among those with high compulsivity, level of affect lability was associated with the number of hard exercise episodes; whereas, among those with low compulsivity, affect lability was not associated with the number of hard exercise episodes. The same pattern of findings emerged for restricted expression; however, this finding approached, but did not reach statistical significance. As such, it appears that affect lability is differentially related to hard exercise among individuals with BN depending upon the level of compulsivity and, to a more limited extent, restricted expression. These results suggest that, for individuals with BN with either compulsivity or restricted expression, focusing treatment on increasing flexibility and/or verbal expression of emotions may help them in the context of intense, fluctuating affect

Subjective and objective binge eating in relation to eating disorder symptomatology, negative affect, and personality dimensions

The current study explored the clinical meaningfulness of distinguishing subjective (SBE) from objective binge eating (OBE) among individuals with threshold/subthreshold bulimia nervosa (BN). We examined relations between OBEs and SBEs and eating disorder symptoms, negative affect, and personality dimensions using both a group comparison and a continuous approach