Complete Genome Sequences of Four Escherichia coli ST95 Isolates from Bloodstream Infections

Finished genome sequences are presented for four Escherichia coli strains isolated from bloodstream infections at San Francisco General Hospital. These strains provide reference sequences for four major fimH-identified sublineages within the multilocus sequence type (MLST) ST95 group, and provide insights into pathogenicity and differential antimicrobial susceptibility within this group

Assessing the appropriateness of the management of otitis media in Australia: A population-based sample survey.

AIM: Acute otitis media (AOM) is the most common infectious disease for which antibiotics are prescribed; its management is costly and has the potential to increase the antimicrobial resistance of this infection. This study measured the levels of adherence to the clinical practice guidelines (CPGs) of AOM and otitis media with effusion (OME) management in Australian children. METHODS: We searched for national and international CPGs relating to AOM and OME in children and created 37 indicators for assessment. We reviewed medical records for adherence to these indicators in 120 locations, across one inpatient and three ambulatory health-care settings. Our review sample was obtained from three Australian states that contain 60% of the nation's children. RESULTS: We reviewed the records of 1063 children with one or more assessments of CPG adherence for otitis media. Of 22 indicators with sufficient data, estimated adherence ranged from 7.4 to 99.1%. Overuse of treatment, particularly overprescribing of antibiotics, was more common than underuse. A frequent lack of adherence with recommended care was observed for children aged between 1 and 2 years with AOM. Adherence varied by health-care setting, with emergency departments and inpatient settings more adherent to CPGs than general practices. CONCLUSIONS: Our assessment of a number of indicators in the common settings in which otitis media is treated found that guideline adherence varied widely between individual indicators. Internationally agreed standards for diagnosis and treatment, coupled with clinician education on the existence and content of CPGs and clinical decision support, are needed to improve the management of children presenting with AOM and OME

Beryllium and Alpha-Element Abundances in a Large Sample of Metal-Poor Stars

The light elements, Li, Be, and B, provide tracers for many aspects of astronomy including stellar structure, Galactic evolution, and cosmology. We have taken spectra of Be in 117 metal-poor stars ranging in metallicity from [Fe/H] = -0.5 to -3.5 with Keck I + HIRES at a resolution of 42,000 and signal-to-noise ratios of near 100. We have determined the stellar parameters spectroscopically from lines of Fe I, Fe II, Ti I and Ti II. The abundances of Be and O were derived by spectrum synthesis techniques, while abundances of Fe, Ti, and Mg were found from many spectral line measurements. There is a linear relationship between [Fe/H] and A(Be) with a slope of +0.88 +-0.03 over three orders of magnitude in [Fe/H]. We fit the relationship between A(Be) and [O/H] with both a single slope and with two slopes. The relationship between [Fe/H] and [O/H] seems robustly linear and we conclude that the slope change in Be vs. O is due to the Be abundance. Although Be is a by-product of CNO, we have used Ti and Mg abundances as alpha-element surrogates for O in part because O abundances are rather sensitive to both stellar temperature and surface gravity. We find that A(Be) tracks [Ti/H] very well with a slope of 1.00 +-0.04. It also tracks [Mg/H] very well with a slope of 0.88 +-0.03. We find that there are distinct differences in the relationships of A(Be) and [Fe/H] and of A(Be) and [O/H] for our dissipative stars and our accretive stars. We suggest that the Be in the dissipative stars was primarily formed by GCR spallation and Be in the accretive stars was formed in the vicinity of SN II.Comment: Accepted for Ap.J. Nov. 10, 2011, v. 741 70 pages, 27 figures, 5 table

Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S), a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites) and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

Adiponectin levels in people with Latent Autoimmune Diabetes-a case control study

<p>Abstract</p> <p>Background</p> <p>To examine adiponectin levels in people with Latent Autoimmune Diabetes in Adults using a matched pair case control study.</p> <p>Findings</p> <p>Patients with LADA (n = 64), were matched for sex with type 2 diabetic and non-diabetic controls. A matched paired T-test was used to examine average adiponectin levels in the LADA patients' versus controls. The average adiponectin level for the LADA patients was 9.96 μg/ml compared to 6.4 μg/ml for Type 2 matched controls and 9.6 μg/ml for non-diabetic controls. Mean difference for the LADA-type 2 comparison was calculated after data was log transformed and showed a difference of 1.58 μg/ml (95%CI: 1.28-1.95, p = 0.0001). There was no significant difference between LADA and non-diabetic controls (p = 0.54).</p> <p>Conclusions</p> <p>Adiponectin levels are higher among people with LADA compared to those with type 2 diabetes and are equivalent to levels seen in non-diabetic controls. This suggests that risk of complications in LADA, as with type 1 diabetes may be related more to glycaemic control rather than to factors of the metabolic syndrome.</p

Nucleotide and phylogenetic analyses of the Chlamydia trachomatis ompA gene indicates it is a hotspot for mutation

<p>Abstract</p> <p>Background</p> <p>Serovars of the human pathogen <it>Chlamydia trachomatis </it>occupy one of three specific tissue niches. Genomic analyses indicate that the serovars have a phylogeny congruent with their pathobiology and have an average substitution rate of less than one nucleotide per kilobase. In contrast, the gene that determines serovar specificity, <it>ompA</it>, has a phylogenetic association that is not congruent with tissue tropism and has a degree of nucleotide variability much higher than other genomic loci. The <it>ompA </it>gene encodes the major surface-exposed antigenic determinant, and the observed nucleotide diversity at the <it>ompA </it>locus is thought to be due to recombination and host immune selection pressure. The possible contribution of a localized increase in mutation rate, however, has not been investigated.</p> <p>Results</p> <p>Nucleotide diversity and phylogenetic relationships of the five constant and four variable domains of the <it>ompA </it>gene, as well as several loci surrounding <it>ompA</it>, were examined for each serovar. The loci flanking the <it>ompA </it>gene demonstrated that nucleotide diversity increased monotonically as <it>ompA </it>is approached and that their gene trees are not congruent with either <it>ompA </it>or tissue tropism. The variable domains of the <it>ompA </it>gene had a very high level of non-synonymous change, which is expected as these regions encode the surface-exposed epitopes and are under positive selection. However, the synonymous changes are clustered in the variable regions compared to the constant domains; if hitchhiking were to account for the increase in synonymous changes, these substitutions should be more evenly distributed across the gene. Recombination also cannot entirely account for this increase as the phylogenetic relationships of the constant and variable domains are congruent with each other.</p> <p>Conclusions</p> <p>The high number of synonymous substitutions observed within the variable domains of <it>ompA </it>appears to be due to an increased mutation rate within this region of the genome, whereas the increase in nucleotide substitution rate and the lack of phylogenetic congruence in the regions flanking <it>ompA </it>are characteristic motifs of gene conversion. Together, the increased mutation rate in the <it>ompA </it>gene, in conjunction with gene conversion and positive selection, results in a high degree of variability that promotes host immune evasion.</p

Designing the climate observing system of the future

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 6 (2018): 80–102, doi:10.1002/2017EF000627.Climate observations are needed to address a large range of important societal issues including sea level rise, droughts, floods, extreme heat events, food security, and freshwater availability in the coming decades. Past, targeted investments in specific climate questions have resulted in tremendous improvements in issues important to human health, security, and infrastructure. However, the current climate observing system was not planned in a comprehensive, focused manner required to adequately address the full range of climate needs. A potential approach to planning the observing system of the future is presented in this article. First, this article proposes that priority be given to the most critical needs as identified within the World Climate Research Program as Grand Challenges. These currently include seven important topics: melting ice and global consequences; clouds, circulation and climate sensitivity; carbon feedbacks in the climate system; understanding and predicting weather and climate extremes; water for the food baskets of the world; regional sea-level change and coastal impacts; and near-term climate prediction. For each Grand Challenge, observations are needed for long-term monitoring, process studies and forecasting capabilities. Second, objective evaluations of proposed observing systems, including satellites, ground-based and in situ observations as well as potentially new, unidentified observational approaches, can quantify the ability to address these climate priorities. And third, investments in effective climate observations will be economically important as they will offer a magnified return on investment that justifies a far greater development of observations to serve society's needs

Prioritization of Epilepsy Associated Candidate Genes by Convergent Analysis

Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research.In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways.The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases