Minimizing the profligacy of searches with reset.

We introduce the profligacy of a search process as a competition between its expected cost and the probability of finding the target. The arbiter of the competition is a parameter λ that represents how much a searcher invests into increasing the chance of success. Minimizing the profligacy with respect to the search strategy specifies the optimal search.

A cross-sectional survey of Department of Veterans Affairs laboratory practices for identification of carbapenem-resistant and .

Control of carbapenem-resistant and spread in healthcare settings begins with timely and accurate laboratory testing practices. Survey results show most Veterans Affairs facilities are performing recommended tests to identify these organisms. Most facilities report sufficient resources to perform testing, though medium-complexity facilities report some perceived barriers.

Tambjamines as Fast-Acting Multistage Antimalarials.

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages.

Energy expenditure, intake and availability in female soccer players via doubly labelled water: Are we misrepresenting low energy availability?

Female soccer players have been identified as presenting with low energy availability (LEA), though the prevalence of LEA may be overestimated given inaccuracies associated with self-reporting dietary intakes. Accordingly, we aimed to quantify total daily energy expenditure (TDEE) via the doubly labelled water (DLW) method, energy intake (EI) and energy availability (EA). Adolescent female soccer players (n = 45; 16 ± 1 years) completed a 9-10 day 'training camp' representing their national team.

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling.

Development and implementation of a nationwide multidrug-resistant organism tracking and alert system for Veterans Affairs medical centers.

Objective: Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.

Methods: An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant (CRE) and methicillin-resistant (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as "VA Bug Alert" (VABA).

Discovery and Optimization of Tambjamines as a Novel Class of Antileishmanial Agents.

Leishmaniasis is a neglected tropical disease that is estimated to afflict over 12 million people. Current drugs for leishmaniasis suffer from serious deficiencies, including toxicity, high cost, modest efficacy, primarily parenteral delivery, and emergence of widespread resistance. We have discovered and developed a natural product-inspired tambjamine chemotype, known to be effective against spp, as a novel class of antileishmanial agents.

Facility- and patient-level factors associated with implementation of contact precautions in hospitalized VA patients with positive CRE cultures.

Decreasing the time to contact precautions (CP) is critical to carbapenem-resistant Enterobacterales (CRE) prevention. Identifying factors associated with delayed CP can decrease the spread from patients with CRE. In this study, a shorter length of stay was associated with being placed in CP within 3 days.

Current fluctuations in a partially asymmetric simple exclusion process with a defect particle.

We study an exclusion process on a ring comprising a free defect particle in a bath of normal particles. The model is one of the few integrable cases in which the bath particles are partially asymmetric. The presence of the free defect creates localized or shock phases according to parameter values.

Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014-2022.

We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-acquired-, and ventilator-associated bacterial pneumonia (CABP, HABP, VABP), complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), and acute bacterial skin and structural infections (ABSSSIs). We reviewed relevant documents from new drug applications (NDA) of FDA-approved antibiotics from 2014-2019 for the above indications. Murine neutropenic thigh infection models supported the choice of a pharmacokinetic-pharmacodynamic (PKPD) target in 11/12 NDAs reviewed.

Treatment effectiveness of antibiotic therapy in Veterans with multidrug-resistant bacteremia.

Objective: To describe antimicrobial therapy used for multidrug-resistant (MDR) bacteremia in Veterans and impacts on mortality.

Methods: This was a retrospective cohort study of hospitalized Veterans Affairs patients from 2012 to 2018 with a positive MDR blood culture who received antimicrobial treatment 2 days prior to through 5 days after the culture date. Only the first culture per patient was used.

Under-Fuelling for the Work Required? Assessment of Dietary Practices and Physical Loading of Adolescent Female Soccer Players during an Intensive International Training and Game Schedule.

Previous studies demonstrate that "under-fuelling" (i.e., reduced carbohydrate (CHO) and energy intake (EI) in relation to recommended guidelines) is prevalent within adult female soccer players, the consequence of which may have acute performance and chronic health implications.

Active Surveillance and Contact Precautions for Preventing Methicillin-Resistant Staphylococcus aureus Healthcare-Associated Infections During the COVID-19 Pandemic.

Background: Statistically significant decreases in methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) occurred in Veterans Affairs (VA) hospitals from 2007 to 2019 using a national policy of active surveillance (AS) for facility admissions and contact precautions for MRSA colonized (CPC) or infected (CPI) patients, but the impact of suspending these measures to free up laboratory resources for testing and conserve personal protective equipment for coronavirus disease 2019 (COVID-19) on MRSA HAI rates is not known.

Methods: From July 2020 to June 2022 all 123 acute care VA hospitals nationwide were given the rolling option to suspend (or re-initiate) any combination of AS, CPC, or CPI each month, and MRSA HAIs in intensive care units (ICUs) and non-ICUs were tracked.

Results: There were 917 591 admissions, 5 225 174 patient-days, and 568 MRSA HAIs.

Systematic Review and Meta-Analysis of the Effect of Loop Diuretics on Antibiotic Pharmacokinetics.

Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several potential drug interactions. A systematic review of the literature was performed to investigate the impact of loop diuretics on antibiotic PK.

Determinants of vaccine acceptance, knowledge, attitude, and prevention practices against COVID-19 among governmental healthcare workers in Addis Ababa and Adama, Ethiopia: A cross-sectional study.

Background And Aims: COVID-19 vaccines are vital tools for infection prevention and control of the pandemic. However, coronavirus immunization requires acceptance among healthcare workforces and by the community. In Ethiopia, studies focused on determinants of vaccine acceptance, knowledge, attitude, and prevention practices (KAP) contrary to the novel coronavirus among healthcare staff are limited.

Increased carbapenemase testing following implementation of national VA guidelines for carbapenem-resistant Enterobacterales (CRE).

Objective: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics.

Design: Retrospective cohort study.

Setting: Department of Veterans' Affairs medical centers (VAMCs).

Lack of correlation between standardized antimicrobial administration ratios (SAARs) and healthcare-facility-onset infection rates in Veterans Affairs medical facilities.

We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.

Normalising the conversation: a qualitative analysis of player and stakeholder perceptions of menstrual health support within elite female soccer.

Purpose: This qualitative study explores player and stakeholder perceptions of menstrual health support in elite female soccer.

Methods: Semi-structured interviews were conducted with 47 participants including players (n = 12), parents (n = 9), coaches (n = 9), sport scientists (n = 7), nutritionists (n = 5) and medical staff (n = 5).

Results: Via thematic analysis, data demonstrate that elite female soccer players experience a range of physical and psychological symptoms primarily at the onset of and during menses (as also perceived by stakeholders), with most participants perceiving these symptoms to impact performance.

Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans.

Background: Carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSI) increase mortality three-fold compared with carbapenem-susceptible bloodstream infections. Because these infections are rare, there is a paucity of information on mortality associated with different treatment regimens. This study examines treatment regimens and association with in-hospital, 30 day and 1 year mortality risk for patients with CRE-BSI.

ERF-related craniosynostosis and surgical management in the paediatric cohort.

Introduction: ERF mutation is one of the most recently identified genetic aberrations associated with syndromic craniosynostosis. Data on the pattern of craniosynostosis, surgical management of ERF-related craniosynostosis and outcomes is limited. We report on our single-centre experience in paediatric cohort of patients with syndromic craniosynostosis secondary to ERF mutation.

Infectious Disease Consults of Bloodstream Infection and Impact on Health Outcomes.

Background: Infectious diseases (ID) consultation improves health outcomes for certain infections but has not been well described for (PA) bloodstream infection (BSI). Therefore, the goal of this study was to examine ID consultation of inpatients with PA BSI and factors impacting outcomes.

Methods: This was a retrospective cohort study from January 1, 2012, to December 31, 2018, of adult hospitalized veterans with PA BSI and antibiotic treatment 2 days before through 5 days after the culture date.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).