We report on a major milestone in the construction of logarithmically accurate final-state parton showers, achieving next-to-next-to-leading-logarithmic (NNLL) accuracy for the wide class of observables known as event shapes. The key to this advance lies in the identification of the relation between critical NNLL analytic resummation ingredients and their parton-shower counterparts. Our analytic discussion is supplemented with numerical tests of the logarithmic accuracy of three shower variants for more than a dozen distinct event-shape observables in Z→qq[over ¯] and Higgs→gg decays.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Fascin cross-links actin filaments (F-actin) into bundles that support tubular membrane protrusions including filopodia and stereocilia. Fascin dysregulation drives aberrant cell migration during metastasis, and fascin inhibitors are under development as cancer therapeutics. Here, we use cryo-EM, cryo-electron tomography coupled with custom denoising and computational modeling to probe human fascin-1's F-actin cross-linking mechanisms across spatial scales.
View Article and Find Full Text PDFBackground: Ensuring antibiotics are prescribed only when necessary is crucial for maintaining their effectiveness and is a key focus of public health initiatives worldwide. In cases of sinusitis, among the most common reasons for antibiotic prescriptions in children, healthcare providers must distinguish between bacterial and viral causes based on clinical signs and symptoms. However, due to the overlap between symptoms of acute sinusitis and viral upper respiratory infections, antibiotics are often over-prescribed.
View Article and Find Full Text PDFBackground: Feedback reports summarizing clinician performance are effective tools for improving antibiotic use in the ambulatory setting, but the effectiveness of feedback reports in the hospital setting is unknown.
Methods: Quasi-experimental study conducted between December 2021 and November 2023 within a pediatric health system measuring the impact of clinician feedback reports delivered by email and reviewed in a monthly meeting on appropriate antibiotic use in children hospitalized with community-acquired pneumonia (CAP). We used an interrupted time series analysis (ITSA) to estimate the immediate change and change over time in the proportion of CAP encounters adherent to validated metrics of antibiotic choice and duration, then used Poisson regression to estimate intervention effect as a risk ratio (RR).
Cells mechanically interface with their surroundings through cytoskeleton-linked adhesions, allowing them to sense physical cues that instruct development and drive diseases such as cancer. Contractile forces generated by myosin motor proteins mediate these mechanical signal transduction processes through unclear protein structural mechanisms. Here, we show that myosin forces elicit structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin.
View Article and Find Full Text PDFBackground: During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials.
View Article and Find Full Text PDFFederal and state governments mandate some health care organizations to implement antibiotic stewardship programs (ASPs). Some early adopters developed model ASPs that have helped set industry standards; other benchmarks will likely be forged in subsequent regulation, legislation, and jurisprudence. This article considers how ASP designs can affect professional autonomy, especially of frontline antibiotic stewards who are usually physicians and pharmacists.
View Article and Find Full Text PDFAntimicrob Steward Healthc Epidemiol
April 2024
We conducted a retrospective study to assess performance of provider-selected antibiotic indication (PSI) in identifying hospitalized adults with community-acquired pneumonia. PSI showed moderate sensitivity (64.4%) and high specificity (96.
View Article and Find Full Text PDFAims: Current data suggest that SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged from an animal source. However, to date, there is insufficient scientific evidence to identify the source of SARS-CoV-2 or to explain the original route of transmission to humans. A wide range of mammalian species have been shown to be susceptible to the virus through experimental infection, and in natural environments when in contact with infected humans.
View Article and Find Full Text PDFBackground: A study previously conducted in primary care practices found that implementation of an educational session and peer comparison feedback was associated with reduced antibiotic prescribing for respiratory tract diagnoses (RTDs). Here, we assess the long-term effects of this intervention on antibiotic prescribing following cessation of feedback.
Methods: RTD encounters were grouped into tiers based on antibiotic prescribing appropriateness: tier 1, almost always indicated; tier 2, possibly indicated; and tier 3, rarely indicated.
Fascin crosslinks actin filaments (F-actin) into bundles that support tubular membrane protrusions including filopodia and stereocilia. Fascin dysregulation drives aberrant cell migration during metastasis, and fascin inhibitors are under development as cancer therapeutics. Here, we use cryo-electron microscopy, cryo-electron tomography coupled with custom denoising, and computational modeling to probe fascin's F-actin crosslinking mechanisms across spatial scales.
View Article and Find Full Text PDFLaboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021.
View Article and Find Full Text PDFIntroduction: Crimean Congo Hemorrhagic Fever (CCHF) virus and Lassa virus (LASV) are zoonotic agents regarded as high-consequence pathogens due to their high case fatality rates. CCHF virus is a vector-borne disease and is transmitted by tick bites. Lassa virus is spread via aerosolization of dried rat urine, ingesting infected rats, and direct contact with or consuming food and water contaminated with rat excreta.
View Article and Find Full Text PDFIntroduction: Foot and mouth disease (FMD) is a highly contagious infection of cloven-hoofed animals. The Biosafety Research Road Map reviewed scientific literature regarding the foot and mouth disease virus (FMDV). This project aims to identify gaps in the data required to conduct evidence-based biorisk assessments, as described by Blacksell et al.
View Article and Find Full Text PDFObjectives: COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain.
View Article and Find Full Text PDFThe accuracy of parton-shower simulations is often a limiting factor in the interpretation of data from high-energy colliders. We present the first formulation of parton showers with accuracy 1 order beyond state-of-the-art next-to-leading logarithms, for classes of observables that are dominantly sensitive to low-energy (soft) emissions, specifically nonglobal observables and subjet multiplicities. This represents a major step toward general next-to-next-to-leading logarithmic accuracy for parton showers.
View Article and Find Full Text PDFAntimicrob Steward Healthc Epidemiol
September 2023
Objective: To determine antibiotic prescribing appropriateness for respiratory tract diagnoses (RTD) by season.
Design: Retrospective cohort study.
Setting: Primary care practices in a university health system.
Introduction: The virus formerly known as monkeypox virus, now called mpoxv, belongs to the Orthopoxvirus genus and can cause mpox disease through both animal-to-human and human-to-human transmission. The unexpected spread of mpoxv among humans has prompted the World Health Organization (WHO) to declare a Public Health Emergency of International Concern (PHEIC).
Methods: We conducted a literature search to identify the gaps in biosafety, focusing on five main areas: how the infection enters the body and spreads, how much of the virus is needed to cause infection, infections acquired in the lab, accidental release of the virus, and strategies for disinfecting and decontaminating the area.
Introduction: The Biosafety Research Road Map reviewed the scientific literature on a viral respiratory pathogen, avian influenza virus, and a bacterial respiratory pathogen, This project aims at identifying gaps in the data required to conduct evidence-based biorisk assessments, as described in Blacksell et al. One significant gap is the need for definitive data on sample aerosolization to guide the selection of engineering controls for diagnostic procedures.
Methods: The literature search focused on five areas: routes of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination methods.
The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats.
View Article and Find Full Text PDFIntroduction: bacteria cause shigellosis, a gastrointestinal infection most often acquired from contaminated food or water.
Methods: In this review, the general characteristics of bacteria are described, cases of laboratory-acquired infections (LAIs) are discussed, and evidence gaps in current biosafety practices are identified.
Results: LAIs are undoubtedly under-reported.
Introduction: The SARS-CoV-2 virus emerged as a novel virus and is the causative agent of the COVID-19 pandemic. It spreads readily human-to-human through droplets and aerosols. The Biosafety Research Roadmap aims to support the application of laboratory biological risk management by providing an evidence base for biosafety measures.
View Article and Find Full Text PDFIntroduction: Lack of evidence-based information regarding potential biological risks can result in inappropriate or excessive biosafety and biosecurity risk-reduction strategies. This can cause unnecessary damage and loss to the physical facilities, physical and psychological well-being of laboratory staff, and community trust. A technical working group from the World Organization for Animal Health (WOAH, formerly OIE), World Health Organization (WHO), and Chatham House collaborated on the Biosafety Research Roadmap (BRM) project.
View Article and Find Full Text PDF