Outcome predictors of uncomplicated sepsis

BACKGROUND: The development of sepsis risk prediction models and treatment guidelines has largely been based on patients presenting in the emergency department (ED) with severe sepsis or septic shock. Therefore, in this study we investigated which patient characteristics might identify patients with an adverse outcome in a heterogeneous group of patients presenting with uncomplicated sepsis to the emergency department (ED). FINDINGS: We performed a retrospective cohort analysis of all ED patients presenting with uncomplicated sepsis in a large teaching hospital during a 3-month period. During this period, 70 patients fulfilled the criteria of uncomplicated sepsis. Eight died in the hospital. Non-survivors were characterized by a higher abbreviated Mortality in Emergency Department Sepsis (MEDS) score (7.2 ± 3.4 vs. 4.8 ± 2.9, p = 0.03) and a lower Hb (6.6 ± 1.2 vs. 7.7 ± 1.4, p = 0.03), and they used beta-blockers more often (75% vs. 19%, p < 0.01). CONCLUSIONS: Non-survivors of uncomplicated sepsis had on average a higher abbreviated MEDS score, a lower hemoglobin (Hb) and more often used β-blockers compared to survivors. Early identification of these factors might contribute to optimization of sepsis treatment for this patient category and thereby prevent disease progression to severe sepsis or septic shock

Composite Fermion Metals from Dyon Black Holes and S-Duality

We propose that string theory in the background of dyon black holes in four-dimensional anti-de Sitter spacetime is holographic dual to conformally invariant composite Dirac fermion metal. By utilizing S-duality map, we show that thermodynamic and transport properties of the black hole match with those of composite fermion metal, exhibiting Fermi liquid-like. Built upon Dirac-Schwinger-Zwanziger quantization condition, we argue that turning on magnetic charges to electric black hole along the orbit of Gamma(2) subgroup of SL(2,Z) is equivalent to attaching even unit of statistical flux quanta to constituent fermions. Being at metallic point, the statistical magnetic flux is interlocked to the background magnetic field. We find supporting evidences for proposed holographic duality from study of internal energy of black hole and probe bulk fermion motion in black hole background. They show good agreement with ground-state energy of composite fermion metal in Thomas-Fermi approximation and cyclotron motion of a constituent or composite fermion excitation near Fermi-point.Comment: 30 pages, v2. 1 figure added, minor typos corrected; v3. revised version to be published in JHE

Immunogenic Mycobacterium africanum Strains Associated with Ongoing Transmission in The Gambia

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative-induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia

Exact Results and Holography of Wilson Loops in N=2 Superconformal (Quiver) Gauge Theories

Using localization, matrix model and saddle-point techniques, we determine exact behavior of circular Wilson loop in N=2 superconformal (quiver) gauge theories. Focusing at planar and large `t Hooft couling limits, we compare its asymptotic behavior with well-known exponential growth of Wilson loop in N=4 super Yang-Mills theory. For theory with gauge group SU(N) coupled to 2N fundamental hypermultiplets, we find that Wilson loop exhibits non-exponential growth -- at most, it can grow a power of `t Hooft coupling. For theory with gauge group SU(N) x SU(N) and bifundamental hypermultiplets, there are two Wilson loops associated with two gauge groups. We find Wilson loop in untwisted sector grows exponentially large as in N=4 super Yang-Mills theory. We then find Wilson loop in twisted sector exhibits non-analytic behavior with respect to difference of two `t Hooft coupling constants. By letting one gauge coupling constant hierarchically larger/smaller than the other, we show that Wilson loops in the second type theory interpolate to Wilson loop in the first type theory. We infer implications of these findings from holographic dual description in terms of minimal surface of dual string worldsheet. We suggest intuitive interpretation that in both type theories holographic dual background must involve string scale geometry even at planar and large `t Hooft coupling limit and that new results found in the gauge theory side are attributable to worldsheet instantons and infinite resummation therein. Our interpretation also indicate that holographic dual of these gauge theories is provided by certain non-critical string theories.Comment: 52 pages, 7 figures v2. more figures embedded v3. minor stylistic changes, v4. published versio

Individuals with Fear of Blushing Explicitly and Automatically Associate Blushing with Social Costs

To explain fear of blushing, it has been proposed that individuals with fear of blushing overestimate the social costs of their blushing. Current information-processing models emphasize the relevance of differentiating between more automatic and more explicit cognitions, as both types of cognitions may independently influence behavior. The present study tested whether individuals with fear of blushing expect blushing to have more negative social consequences than controls, both on an explicit level and on a more automatic level. Automatic associations between blushing and social costs were assessed in a treatment-seeking sample of individuals with fear of blushing who met DSM-IV criteria for social anxiety disorder (n = 49) and a non-anxious control group (n = 27) using a single-target Implicit Association Test (stIAT). In addition, participants’ explicit expectations about the social costs of their blushing were assessed. Individuals with fear of blushing showed stronger associations between blushing and negative outcomes, as indicated by both stIAT and self-report. The findings support the view that automatic and explicit associations between blushing and social costs may both help to enhance our understanding of the cognitive processes that underlie fear of blushing

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

‘Free’ inhibin α subunit is expressed by bovine ovarian theca cells and its knockdown suppresses androgen production

Inhibins are ovarian dimeric glycoprotein hormones that suppress pituitary FSH production. They are synthesised by follicular granulosa cells as α plus βA/βB subunits (encoded by INHA, INHBA, INHBB, respectively). Inhibin concentrations are high in follicular fluid (FF) which is also abundant in ‘free’ α subunit, presumed to be of granulosal origin, but its role(s) remains obscure. Here, we report the unexpected finding that bovine theca cells show abundant INHA expression and ‘free’ inhibin α production. Thus, theca cells may contribute significantly to the inhibin α content of FF and peripheral blood. In vitro, knockdown of thecal INHA inhibited INSL3 and CYP17A1 expression and androgen production while INSL3 knockdown reduced INHA and inhibin α secretion. These findings suggest a positive role of thecal inhibin α on androgen production. However, exogenous inhibin α did not raise androgen production. We hypothesised that inhibin α may modulate the opposing effects of BMP and inhibin on androgen production. However, this was not supported experimentally. Furthermore, neither circulating nor intrafollicular androgen concentrations differed between control and inhibin α-immunized heifers, casting further doubt on thecal inhibin α subunit having a significant role in modulating androgen production. Role(s), if any, played by thecal inhibin α remain elusive

Stage-specific fluorescence intensity of GFP and mCherry during sporulation In Bacillus Subtilis

<p>Abstract</p> <p>Background</p> <p>Fluorescent proteins are powerful molecular biology tools that have been used to study the subcellular dynamics of proteins within live cells for well over a decade. Two fluorescent proteins commonly used to enable dual protein labelling are GFP (green) and mCherry (red). Sporulation in the Gram positive bacterium <it>Bacillus subtilis </it>has been studied for many years as a paradigm for understanding the molecular basis for differential gene expression. As sporulation initiates, cells undergo an asymmetric division leading to differential gene expression in the small prespore and large mother cell compartments. Use of two fluorescent protein reporters permits time resolved examination of differential gene expression either in the same compartments or between compartments. Due to the spectral properties of GFP and mCherry, they are considered an ideal combination for co-localisation and co-expression experiments. They can also be used in combination with fluorescent DNA stains such as DAPI to correlate protein localisation patterns with the developmental stage of sporulation which can be linked to well characterised changes in DNA staining patterns.</p> <p>Findings</p> <p>While observing the recruitment of the transcription machinery into the forespore of sporulating <it>Bacillus subtilis</it>, we noticed the occurrence of stage-specific fluorescence intensity differences between GFP and mCherry. During vegetative growth and the initial stages of sporulation, fluorescence from both GFP and mCherry fusions behaved similarly. During stage II-III of sporulation we found that mCherry fluorescence was considerably diminished, whilst GFP signals remained clearly visible. This fluorescence pattern reversed during the final stage of sporulation with strong mCherry and low GFP fluorescence. These trends were observed in reciprocal tagging experiments indicating a direct effect of sporulation on fluorescent protein fluorophores.</p> <p>Conclusions</p> <p>Great care should be taken when interpreting the results of protein localisation and quantitative gene expression patterns using fluorescent proteins in experiments involving intracellular physiological change. We believe changes in the subcellular environment of the sporulating cell leads to conditions that differently alter the spectral properties of GFP and mCherry making an accurate interpretation of expression profiles technically challenging.</p

Gene Flow between the Korean Peninsula and Its Neighboring Countries

SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern ( = 16) and Southern ( = 3) Asians, Amerindians ( = 1), and four HapMap populations (YRI, CEU, JPT, and CHB). Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies. Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics. By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia. In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages