Vaccine message framing and parents' intent to immunize their infants for MMR

BACKGROUND AND OBJECTIVE: Emphasizing societal benefits of vaccines has been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children. The objective was to determine whether emphasizing the benefits of measles-mumps-rubella (MMR) vaccination directly to the vaccine recipient or to society differentially impacts parents' vaccine intentions for their infants. METHODS: In a national online survey, parents (N = 802) of infants <12 months old were randomly assigned to receive 1 of 4 MMR vaccine messages: (1) the Centers for Disease Control and Prevention Vaccine Information Statement (VIS), (2) VIS and information emphasizing the MMR vaccine's benefits to the child, (3) VIS and information emphasizing societal benefits, or (4) VIS and information emphasizing benefits both to the child and society. Parents reported their likelihood of vaccinating their infants for MMR on a response scale of 0 (extremely unlikely) to 100 (extremely likely). RESULTS: Compared with the VIS-only group (mean intention = 86.3), parents reported increased vaccine intentions for their infants when receiving additional information emphasizing the MMR vaccine's benefits either directly to the child (mean intention = 91.6, P = .01) or to both the child and society (mean intention = 90.8, P = .03). Emphasizing the MMR vaccine's benefits only to society did not increase intentions (mean intention = 86.4, P = .97). CONCLUSIONS: We did not see increases in parents' MMR vaccine intentions for their infants when societal benefits were emphasized without mention of benefits directly to the child. This finding suggests that providers should emphasize benefits directly to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child

Mapping the packaging cleavage determinants in the phage-dependent Staphylococcus aureus pathogenicity island SaPI1

Members of the SaPI family of Staphylococcus aureus pathogenicity islands are highly mobile, superantigen-encoding genetic elements that depend upon specific helper bacteriophages for their horizontal transfer. Following helper phage infection, these elements excise, replicate, and package their genomes in virions provided by the helper phage. One of the novel features of this process is the use of a SaPI-encoded small subunit of terminase, which replaces the phage small terminase subunit and redirects terminase packaging specificity to SaPI DNA. The SaPI genome, like that of the helper phage, is packaged from concatemers by a headful packaging mechanism, resulting in encapsidated DNA molecules that exhibit terminal redundancy and partial circular permutation. In this study we have localized the site of initial cleavage in SaPI1, a prototype member of this family, and have defined a small region of the SaPI1 genome sufficient for specific packaging. The cleavage site was initially localized to an intergenic region upstream of SaPI1 operon 1 by identification of submolar fragments in restricted SaPI1 virion DNA. Ligation of linkers to the ends of SaPI virion DNA, followed by amplification and sequencing of the linker/SaPI1 junction, further defined the sites of initial cleavage. A fragment encompassing this region was cloned into a plasmid vector co-expressing SaPI1 small terminase and shown to confer high frequency plasmid transduction by helper phage 80α. The critical determinants for SaPI1-specific packaging were further defined by deletion analysis of the cloned fragment. These results demonstrate that the sequence required for SaPI1-specific packaging maps to a small region upstream of the promoter for SaPI1 operon 1. This is strikingly different from the pac site used by the helper phage terminase, which, like other phage pac sites, maps to within the small terminase gene itself

Sequence determinants for DNA packaging specificity in the S. aureus pathogenicity island SaPI1

The SaPIs and their relatives are a family of genomic islands that exploit helper phages for high frequency horizontal transfer. One of the mechanisms used by SaPIs to accomplish this molecular piracy is the redirection of the helper phage DNA packaging machinery. SaPIs encode a small terminase subunit that can be substituted for that of the phage. In this study we have determined the initial packaging cleavage sites for helper phage 80α, which uses the phage-encoded small terminase subunit, and for SaPI1, which uses the SaPI-encoded small terminase subunit. We have identified a 19 nt SaPI1 sequence that is necessary and sufficient to allow high frequency 80α transduction of a plasmid by a terminase carrying the SaPI1-encoded small subunit. We also show that the hybrid enzyme with the SaPI1 small terminase subunit is capable of generalized transduction.This work was performed in part under FDA's Medical Countermeasures Initiative, Contract #HHSF2232010000521 and NIH 1R56 AI081837 (to GEC). JCB was supported by the Portuguese Institute Fundacao para a Ciencia e Tecnologia (FCT), PhD Fellowship SFRH/BD/66250/2009. E.K.R. was supported by the National Academies National Research Council; his contribution to this study was carried out at NICHHD, NIH, Bethesda, MD, in the laboratory of the late Robert A. Weisberg. Plasmid pCN51 (in strain NRS613) and strain RN4282 (NRS145) were obtained through the Network of Antimicrobial Resistance in Staphylococcus aureus (NARSA) program supported under NIAID/NIFI contract #HHSN272200700055C

Renin-angiotensin system blockers and susceptibility to COVID-19:an international, open science, cohort analysis

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension.Methods: In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.Findings: Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of &gt;40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons.Interpretation: No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19.</p

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom

Altres ajuts: This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Center (BRC), US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV016201 and INV-019257). APU has received funding from the Medical Research Council (MRC) [MR/K501256/1, MR/N013468/1] and Fundación Alfonso Martín Escudero (FAME) (APU). VINCI [VA HSR RES 13-457] (SLD, MEM, KEL). JCEL has received funding from the Medical Research Council (MR/K501256/1) and Versus Arthritis (21605). MR is funded by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program [grant number: 2017/1630]A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8−40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0−33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies

An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science

Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings

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Your Resting Brain CAREs about Your Risky Behavior

Research on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking.We employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex.Task-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors