Singularities of Schubert Varieties within a Right Cell

We describe an algorithm which pattern embeds, in the sense of Woo-Yong, any Bruhat interval of a symmetric group into an interval whose extremes lie in the same right Kazhdan-Lusztig cell. This apparently harmless fact has applications in finding examples of reducible associated varieties of $\mathfrak{sl}_n$-highest weight modules, as well as in the study of $W$-graphs for symmetric groups, and in comparing various bases of irreducible representations of the symmetric group or its Hecke algebra. For example, we are able to systematically produce many negative answers to a question from the 1980s of Borho-Brylinski and Joseph, which had been settled by Williamson via computer calculations only in 2014

Effect of tecovirimat on healing time and viral clearance by emulation of a target trial in patients hospitalized for mpox

Tecovirimat is a treatment option for severe mpox, although randomized clinical trials are ongoing. The aim of the study is to assess the effect of tecovirimat on healing time and the extent of viral clearance by target trial emulation using observational data. Clinical and virological data of patients hospitalized for mpox were collected. Samples from the upper respiratory tract (URT) were grouped in two time points: T1 (median 6 days from symptoms onset) and T2 (median 5 days from T1). Patients were followed-up until recovery. Average treatment effect (ATE) in patients untreated versus treated with tecovirimat was estimated on time to healing and variation in viral load in URT, using a weighted and cloning analysis. Among the 41 patients included, 19 completed a course of tecovirimat. The median time from symptoms onset to hospitalization and to drug-starting was 4 days and 10 days, respectively. No improvement in healing time in treated versus untreated was observed. No difference by treatment group in time to viral clearance was detected by ATE fitted in a subset of 13 patients after controlling for confounders. We found no evidence for a large effect of tecovirimat in shortening healing time and viral clearance. While awaiting the results of randomized studies, the use of tecovirimat should be restricted to the clinical trial setting

Clinicians' attitude towards a placebo-controlled randomised clinical trial investigating the effect of neuraminidase inhibitors in adults hospitalised with influenza

Background: The value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza. Methods: Senior clinicians (n=50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey. Participants were asked their opinion on the evidence for benefit of NAIs in influenza, their current practice in relation to: a) testing for influenza; b) treating empirically with NAIs; and c) when influenza infection is virolologically confirmed, prescribing NAIs. Results: Thirty-five (70%) of 50 clinicians completed the survey. Respondents were drawn mainly from infectious diseases, intensive care and respiratory medicine. Only 11 (31%) of 35 respondents agreed that NAIs are effective at reducing influenza mortality;14(40%)disagreed, 10 (28.6%) neither agreed nor disagreed. When managing adults admitted to non-ICU wards with a respiratory infection during an influenza season, 15 (51.7%) clinicians indicated they would usually perform a test for influenza in greater than 60% of patients but only 9 (31%) would treat empirically with NAIs in greater than 60% of patients. Few clinicians would either test or empirically treat patients presenting with other (non-respiratory infection related) diagnoses. If influenza infection is confirmed, 17 (64.5%) clinicians would prescribe NAIs in greater than 80% of patients with a respiratory infection treated on non-ICU wards Thirty-one (89%) clinicians agreed that a placebo-controlled clinical trial should be conducted and 29 (85%) would participate in such a trial. Conclusions: There is strong support from UK clinicians for a placebo-controlled trial of NAI treatment in adults hospitalised with suspected influenza. Current variation in medical opinion and clinical practice demonstrates collective equipoise, supporting ethical justification for a trial. Low use of NAIs in the UK suggests randomisation of treatment would not substantially divert patients towards placebo

Spectral Decomposition of Regulatory Thresholds for Climate-Driven Fluctuations in Hydro- and Wind Power Availability

Abstract Climate-driven fluctuations in the runoff and potential energy of surface water are generally large in comparison to the capacity of hydropower regulation, particularly when hydropower is used to balance the electricity production from covarying renewable energy sources such as wind power. To define the bounds of reservoir storage capacity, we introduce a dedicated reservoir volume that aggregates the storage capacity of several reservoirs to handle runoff from specific watersheds. We show how the storage bounds can be related to a spectrum of the climate-driven modes of variability in water availability and to the covariation between water and wind availability. A regional case study of the entire hydropower system in Sweden indicates that the longest regulation period possible to consider spans from a few days of individual subwatersheds up to several years, with an average limit of a couple of months. Watershed damping of the runoff substantially increases the longest considered regulation period and capacity. The high covariance found between the potential energy of the surface water and wind energy significantly reduces the longest considered regulation period when hydropower is used to balance the fluctuating wind power

Ebola: missed opportunities for Europe-Africa research

The current unprecedented Ebola virus disease outbreak in parts of west Africa, which has caused more than 11 200 deaths, has emphasised how the medical and scientific communities lack specific pathways for tackling relevant logistical, design, and ethical issues for assessment of novel diagnostics, treatments, and vaccines through implementation of appropriate clinical trials.1,2 The phenomenal outbreak arose because of several weaknesses in local, regional, and international public health responses, which delayed provision and implementation of effective interventions

Community-based provision of direct-acting antiviral therapy for hepatitis C: Study protocol and challenges of a randomized controlled trial

Background: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment. Methods: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy. Discussion: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV

Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study

Background Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease

Patient to patient transmission of hepatitis B virus: a systematic review of reports on outbreaks between 1992 and 2007

<p>Abstract</p> <p>Background</p> <p>Hepatitis B outbreaks in healthcare settings are still a serious public health concern in high-income countries. To elucidate the most frequent infection pathways and clinical settings involved, we performed a systematic review of hepatitis B virus outbreaks published between 1992 and 2007 within the EU and USA.</p> <p>Methods</p> <p>The research was performed using two different databases: the PubMed Database and the Outbreak Database, the worldwide database for nosocomial outbreaks. Selection of papers was carried out using the Quorom algorithm, and to avoid selection biases, the inclusion criteria were established before the articles were identified.</p> <p>Results</p> <p>Overall, 30 papers were analyzed, reporting on 33 hepatitis B virus outbreaks that involved 471 patients, with 16 fatal cases. Dialysis units accounted for 30.3% of outbreaks followed by medical wards (21.2%), nursing homes (21.2%), surgery wards (15.2), and outpatient clinics (12.1%). The transmission pathways were: multi-vial drugs (30.3%), non-disposable multi-patient capillary blood sampling devices (27.2%), transvenous endomyocardial biopsy procedures (9.1%), and multiple deficiencies in applying standard precautions (9.1%).</p> <p>Conclusion</p> <p>The analysis of transmission pathways showed that some breaches in infection control measures, such as administration of drugs using multi-vial compounds and capillary blood sampling, are the most frequent routes for patient-to-patient transmission of hepatitis B virus. Moreover some outbreak reports underlined that heart-transplant recipients are at risk of contracting hepatitis B virus infection during the transvenous endomyocardial biopsy procedure through indirect contact with infected blood as a result of environmental contamination. To prevent transmission, healthcare workers must adhere to standard precautions and follow fundamental infection control principles, such as the use of sterile, single-use, disposable needles and avoiding the use of multi-vial compounds in all healthcare settings including outpatient settings.</p

Dual recognition of CENP-A nucleosomes is required for centromere assembly

CENP-C and CENP-N recognize distinct structural elements of CENP-A nucleosomes, providing a foundation for the assembly of other centromere and kinetochore components