Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage

Bacteriophage (phage) are both predators and evolutionary drivers for bacteria, notably contributing to the spread of antimicrobial resistance (AMR) genes by generalized transduction. Our current understanding of this complex relationship is limited. We used an interdisciplinary approach to quantify how these interacting dynamics can lead to the evolution of multidrug-resistant bacteria. We cocultured two strains of methicillin-resistant Staphylococcus aureus, each harboring a different antibiotic resistance gene, with generalized transducing phage. After a growth phase of 8 h, bacteria and phage surprisingly coexisted at a stable equilibrium in our culture, the level of which was dependent on the starting concentration of phage. We detected double-resistant bacteria as early as 7 h, indicating that transduction of AMR genes had occurred. We developed multiple mathematical models of the bacteria and phage relationship and found that phage-bacteria dynamics were best captured by a model in which phage burst size decreases as the bacteria population reaches stationary phase and where phage predation is frequency-dependent. We estimated that one in every 108 new phage generated was a transducing phage carrying an AMR gene and that double-resistant bacteria were always predominantly generated by transduction rather than by growth. Our results suggest a shift in how we understand and model phage-bacteria dynamics. Although rates of generalized transduction could be interpreted as too rare to be significant, they are sufficient in our system to consistently lead to the evolution of multidrug-resistant bacteria. Currently, the potential of phage to contribute to the growing burden of AMR is likely underestimated

Medicaid Expenditures on Psychotropic Medications for Children in the Child Welfare System

Abstract Objective: Children in the child welfare system are the most expensive child population to insure for their mental health needs. The objective of this article is to estimate the amount of Medicaid expenditures incurred from the purchase of psychotropic drugs ? the primary drivers of mental health expenditures ? for these children. Methods: We linked a subsample of children interviewed in the first nationally representative survey of children coming into contact with U.S. child welfare agencies, the National Survey of Child and Adolescent Well-Being (NSCAW), to their Medicaid claims files obtained from the Medicaid Analytic Extract. Our data consist of children living in 14 states, and Medicaid claims for 4 years, adjusted to 2010 dollars. We compared expenditures on psychotropic medications in the NSCAW sample to a propensity score-matched comparison sample obtained from Medicaid files. Results: Children surveyed in NSCAW had over thrice the odds of any psychotropic drug use than the comparison sample. Each maltreated child increased Medicaid expenditures by between $237 and$840 per year, relative to comparison children also receiving medications. Increased expenditures on antidepressants and amphetamine-like stimulants were the primary drivers of these increased expenditures. On average, an African American child in NSCAW received $399 less expenditure than a white child, controlling for behavioral problems and other child and regional characteristics. Children scoring in the clinical range of the Child Behavior Checklist received, on average,$853 increased expenditure on psychotropic drugs. Conclusion: Each child with child welfare involvement is likely to incur upwards of $1482 in psychotropic medication expenditures throughout his or her enrollment in Medicaid. Medicaid agencies should focus their cost-containment strategies on antidepressants and amphetamine-type stimulants, and expand use of instruments such as the Child Behavior Checklist to identify high-cost children. Both of these strategies can assist Medicaid agencies to better predict and plan for these expenditures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98497/1/cap%2E2011%2E0135.pd

Smoke consequences of new wildfire regimes driven by climate change

Smoke from wildfires has adverse biological and social consequences, and various lines of evidence suggest that smoke from wildfires in the future may be more intense and widespread, demanding that methods be developed to address its effects on people, ecosystems, and the atmosphere. In this paper, we present the essential ingredients of a modeling system for projecting smoke consequences in a rapidly warming climate that is expected to change wildfire regimes significantly. We describe each component of the system, offer suggestions for the elements of a modeling agenda, and provide some general guidelines for making choices among potential components. We address a prospective audience of researchers whom we expect to be fluent already in building some or many of these components, so we neither prescribe nor advocate particular models or software. Instead, our intent is to highlight fruitful ways of thinking about the task as a whole and its components, while providing substantial, if not exhaustive, documentation from the primary literature as reference. This paper provides a guide to the complexities of smoke modeling under climate change, and a research agenda for developing a modeling system that is equal to the task while being feasible with current resources

Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Development and recent progress on ammonia synthesis catalysts for Haber–Bosch process

Due to its essential use as a fertilizer, ammonia synthesis from nitrogen and hydrogen is considered to be one of the most important chemical processes of the last 100 years. Since then, an enormous amount of work has been undertaken to investigate and develop effective catalysts for this process. Although the catalytic synthesis of ammonia has been extensively studied in the last century, many new catalysts are still currently being developed to reduce the operating temperature and pressure of the process and to improve the conversion of reactants to ammonia. New catalysts for the Haber–Bosch process are the key to achieving green ammonia production in the foreseeable future. Herein, the history of ammonia synthesis catalyst development is briefly described as well as recent progress in catalyst development with the aim of building an overview of the current state of ammonia synthesis catalysts for the Haber–Bosch process. The new emerging ammonia synthesis catalysts, including electride, hydride, amide, perovskite oxide hydride/oxynitride hydride, nitride, and oxide promoted metals such as Fe, Co, and Ni, are promising alternatives to the conventional fused‐Fe and promoted‐Ru catalysts for existing ammonia synthesis plants and future distributed green ammonia synthesis based on the Haber–Bosch process

aj-clements/Vivli-AMR-KG

Repository for code and data produced for the KG submission to the Vivli AMR Data Challenge

The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors

Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0·006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma

Evaluating the impact of a UK recovery college on mental well-being: pre- and post-intervention study

Background Recovery colleges provide personalised educational mental health support for people who self-refer. The research evidence supporting them is growing, with key components and the positive experiences of attendees reported. However, the quantitative outcome evidence and impact on economic outcomes is limited. Aims To evaluate the impact of attending a UK recovery college for students who receive a full educational intervention. Method This is a pre- and post-intervention study, with predominantly quantitative methods. Participants recruited over an 18-month period (01.2020–07.2021) completed self-reported well-being (Short Warwick–Edinburgh Mental Wellbeing Scale (SWEMWBS)) and recovery (Process of Recovery (QPR)) surveys, and provided details and evidence of employment and educational status. Descriptive statistics for baseline data and Shapiro–Wilk, Wilcoxon signed-rank and paired t-tests were used to compare pre- and post-intervention scores, with Hedges’ g-statistic as a measure of effect size. Medical records were reviewed and a brief qualitative assessment of changes reported by students was conducted. Results Of 101 student research participants, 84 completed the intervention. Well-being (mean SWEMWBS scores 17.3 and 21.9; n = 80) and recovery (mean QPR scores 27.2 and 38.8; n = 75) improved significantly (P &lt; 0.001; Hedges’ g of 1.08 and 1.03). The number of economically inactive students reduced from 53 (69%) to 19 (24.4%). No research participants were referred for specialist mental health support while students. ‘Within-self’ and ‘practical’ changes were described by students following the intervention. Conclusions Findings detail the largest self-reported pre–post data-set for students attending a recovery college, and the first data detailing outcomes of remote delivery of a recovery college. </jats:sec

Human challenge trials in vaccine development, Rockville, MD, USA, September 28-30, 2017.

Item does not contain fulltextThe International Alliance for Biological Standardization organized the second workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The objective of this meeting was to examine the use of HCT, in response to the continuing human suffering caused by infectious diseases, preventable by the development of new and improved vaccines. For this, the approach of HCT could be valuable, as HCT can provide key safety, tolerability, immunogenicity, and efficacy data, and can be used to study host-pathogen biology. HCT can generate these data with speed, efficiency and minimal expense, albeit not with the same level of robustness as clinical trials. Incorporated wisely into a clinical development plan, HCT can support optimization or down-selection of new vaccine candidates, assuring that only the worthiest candidates progress to field testing. HCT may also provide pivotal efficacy data in support of licensure, particularly when field efficacy studies are not feasible. Many aspects of HCT were discussed by the participants, including new and existing models, standardization and ethics. A consensus was achieved that HCT, if ethically justified and performed with careful attention to safety and informed consent, should be pursued to promote and accelerate vaccine development.1 september 201