Draft Genome Sequences of Antibiotic-Resistant Commensal Escherichia coli

Antimicrobial resistance is a significant public health issue. We report here the draft genome sequences of three drug-resistant strains of commensal Escherichia coli isolated from a single healthy college student. Each strain has a distinct genome, but two of the three contain an identical large plasmid with multiple resistance genes

Modelling Child Poverty and Wellbeing the Treasury’s TAWA microsimulation model

Large tax–transfer microsimulation models can play a key role in guiding tax–transfer analysis and reform. This article discusses the Treasury’s microsimulation model of the tax–transfer system (the Tax and Welfare Analysis (TAWA) model), including how it is used and the standard outputs it produces. The article also considers whether these standard outputs continue to be fit for purpose. This includes a discussion of different ways of estimating poverty impacts, the role reporting should give to financial incentives to work, and the opportunities provided by improved data. This final point is particularly important for understanding take-up and the prospect for extending the model to cover non-financial measures

Regulation of D-galacturonate metabolism in Caulobacter crescentus by HumR, a LacI-family transcriptional repressor

The oligotrophic freshwater bacterium Caulobacter crescentus encodes a cluster of genes (CC_1487 to CC_1495) shown here to be necessary for metabolism of D-galacturonate, the primary constituent of pectin, a major plant polymer. Sequence analysis suggests that these genes encode a version of the bacterial hexuronate isomerase pathway. A conserved 14 bp sequence motif is associated with promoter regions of three operons within this cluster, and is conserved in homologous gene clusters in related alpha-Proteobacteria. Embedded in the hexuronate gene cluster is a gene (CC_1489) encoding a member of the LacI family of bacterial transcription factors. This gene product, designated here as HumR (hexuronate metabolism regulator), represses expression of the uxaA and uxaC operon promoters by binding to the conserved operator sequence. Repression is relieved in the presence of galacturonate or, to a lesser extent, by glucuronate. Other genes potentially involved in pectin degradation and hexuronate transport are also under the control of HumR. Adoption of a LacI-type repressor to control hexuronate metabolism parallels the regulation of xylose, glucose, and maltose utilization in C. crescentus, but is distinct from the use of GntR-type repressors to control pectin and hexuronate utilization in gamma-Proteobacteria such as Escherichia coli

To look or not to look during vaccination: A pilot randomized trial

Background: Clinicians commonly advise patients to look away from the needle during vaccinations; however, this recommendation is not evidence based. Aim: The aim of this study was to determine whether looking at the needle versus looking away affects pain and fear during vaccinations in adults. Methods: This was a pilot randomized two-group parallel trial with university students receiving influenza vaccinations. Participants were stratified according to their initial needle-looking preference and randomly assigned to either look at versus away from the needle. Participants self-reported their pain and fear during vaccination. Results: Of the 184 subjects who agreed to participate, 160 were enrolled; 66% were female. A three-way analysis of variance (ANOVA; Looking allocation assignment × Looking preference × Sex) revealed a significant main effect of looking allocation assignment on fear (P = 0.025); those who were randomized to look had higher fear scores than those who were randomized to look away. There was also a significant main effect of looking preference on fear (P \u3c 0.001); those who preferred to look away had higher fear scores than those who preferred to look. There was no evidence of an effect of looking allocation assignment or looking preference on pain. There was a significant main effect of sex on fear and pain, with females reporting higher pain and fear scores than males (P = 0.017 and P = 0.001, respectively). There were no significant interactions. Conclusion: These preliminary findings suggest that advising individuals to look away from the needle reduces fear. A larger trial including more individuals and a different population is recommended to confirm the results

Surface cloud forcing in the East Pacific stratus deck/cold tongue/ITCZ complex

Author Posting. © American Meteorological Society 2006. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 19 (2006): 392–409, doi:10.1175/JCLI3620.1.Data from the Eastern Pacific Investigation of Climate Studies (EPIC) mooring array are used to evaluate the annual cycle of surface cloud forcing in the far eastern Pacific stratus cloud deck/cold tongue/intertropical convergence zone complex. Data include downwelling surface solar and longwave radiation from 10 EPIC-enhanced Tropical Atmosphere Ocean (TAO) moorings from 8°S, 95°W to 12°N, 95°W, and the Woods Hole Improved Meteorology (IMET) mooring in the stratus cloud deck region at 20°S, 85°W. Surface cloud forcing is defined as the observed downwelling radiation at the surface minus the clear-sky value. Solar cloud forcing and longwave cloud forcing are anticorrelated at all latitudes from 12°N to 20°S: clouds tended to reduce the downward solar radiation and to a lesser extent increase the downward longwave radiation at the surface. The relative amount of solar radiation reduction and longwave increase depends upon cloud type and varies with latitude. A statistical relationship between solar and longwave surface cloud forcing is developed for rainy and dry periods and for the full record length in six latitudinal regions: northeast tropical warm pool, ITCZ, frontal zone, cold tongue, southern, and stratus deck regions. The buoy cloud forcing observations and empirical relations are compared with the International Satellite Cloud Climatology Project (ISCCP) radiative flux data (FD) dataset and are used as benchmarks to evaluate surface cloud forcing in the NCEP Reanalysis 2 (NCEP2) and 40-yr ECMWF Re-Analysis (ERA-40). ERA-40 and NCEP2 cloud forcing (both solar and longwave) showed large discrepancies with observations, being too large in the ITCZ and equatorial regions and too weak under the stratus deck at 20°S and north to the equator during the cool season from July to December. In particular the NCEP2 cloud forcing at the equator was nearly identical to the ITCZ region and thus had significantly larger solar cloud forcing and smaller longwave cloud forcing than observed. The net result of the solar and longwave cloud forcing deviations is that there is too little radiative warming in the ITCZ and southward to 8°S during the warm season and too much radiative warming under the stratus deck at 20°S and northward to the equator during the cold season.This research was supported by grants from the NOAA Office of Global Programs, Pan American Climate Studies

Histone Methylation by NUE, a Novel Nuclear Effector of the Intracellular Pathogen Chlamydia trachomatis

Sequence analysis of the genome of the strict intracellular pathogen Chlamydia trachomatis revealed the presence of a SET domain containing protein, proteins that primarily function as histone methyltransferases. In these studies, we demonstrated secretion of this protein via a type III secretion mechanism. During infection, the protein is translocated to the host cell nucleus and associates with chromatin. We therefore named the protein nuclear effector (NUE). Expression of NUE in mammalian cells by transfection reconstituted nuclear targeting and chromatin association. In vitro methylation assays confirmed NUE is a histone methyltransferase that targets histones H2B, H3 and H4 and itself (automethylation). Mutants deficient in automethylation demonstrated diminished activity towards histones suggesting automethylation functions to enhance enzymatic activity. Thus, NUE is secreted by Chlamydia, translocates to the host cell nucleus and has enzymatic activity towards eukaryotic substrates. This work is the first description of a bacterial effector that directly targets mammalian histones

Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer

Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Art of the Possible. Data-Driven Insights into Child Poverty in New Zealand

A central goal of income support policies is to reduce the number of families below a minimum standard of living; in other words, to reduce the number of people in poverty. But one challenge is that there is no single measure of what it means to be poor. This article outlines an experimental approach that uses the available data to provide insights into the different dimensions of poverty. It applies a statistical algorithm to three poverty indicators to identify seven different categories of children in poverty, and describes the characteristics of children in each group