Early life mental health and problematic drinking in mid-adulthood: evidence from two British birth cohorts

PURPOSE: Accumulating evidence suggests that externalising problems are consistently associated with alcohol use behaviours, but findings are inconsistent regarding the role of internalising problems. We investigate whether externalising and internalising problems are associated with problematic drinking in mid-adulthood, and whether potential associations are modified by age, sex and cohort. METHODS: The National Child Development Study (NCDS58, n = 17,633) and 1970 British Cohort Study (BCS70, n = 17,568) recruited new-borns in Great Britain in a single week in 1958 and 1970. Mental health was assessed with the Rutter Behaviour Questionnaire at ages 7, 11, and 16 in NCDS58 and ages 5, 10 and 16 in BCS70. Problematic drinking was measured with the CAGE questionnaire at age 33 in NCDS58 and age 34 in BCS70, and the AUDIT scale at age 44/45 in NCDS58 and age 46 in BCS70. Latent scores of externalising and internalising problems were added chronologically into lagged logistic regression models. RESULTS: Externalising and internalising problems were associated in opposite directions with problematic drinking in mid-adulthood. Externalising was a risk factor (OR [95% CI] ranging from 1.06 [1.03, 1.10] to 1.11 [1.07, 1.15] for different ages), and internalising was a protective factor (OR [95% CI] ranging from 0.95 [0.92, 0.99] to 0.90 [0.86, 0.94] for different ages). Associations between early life mental health and mid-adulthood problematic drinking did not differ by developmental timing but were stronger in males. CONCLUSION: Our study provides new insights on links of externalising and internalising difficulties with alcohol use and has implications for public policy in the UK

Treatment of Neuroblastoma with an Engineered “Obligate” Anaerobic Salmonella typhimurium Strain YB1

published_or_final_versio

Probing Shadowed Nuclear Sea with Massive Gauge Bosons in the Future Heavy-Ion Collisions

The production of the massive bosons $Z^0$ and $W^{\pm}$ could provide an excellent tool to study cold nuclear matter effects and the modifications of nuclear parton distribution functions (nPDFs) relative to parton distribution functions (PDFs) of a free proton in high energy nuclear reactions at the LHC as well as in heavy-ion collisions (HIC) with much higher center-of mass energies available in the future colliders. In this paper we calculate the rapidity and transverse momentum distributions of the vector boson and their nuclear modification factors in p+Pb collisions at $\sqrt{s_{NN}}=63$TeV and in Pb+Pb collisions at $\sqrt{s_{NN}}=39$TeV in the framework of perturbative QCD by utilizing three parametrization sets of nPDFs: EPS09, DSSZ and nCTEQ. It is found that in heavy-ion collisions at such high colliding energies, both the rapidity distribution and the transverse momentum spectrum of vector bosons are considerably suppressed in wide kinematic regions with respect to p+p reactions due to large nuclear shadowing effect. We demonstrate that in the massive vector boson productions processes with sea quarks in the initial-state may give more contributions than those with valence quarks in the initial-state, therefore in future heavy-ion collisions the isospin effect is less pronounced and the charge asymmetry of W boson will be reduced significantly as compared to that at the LHC. Large difference between results with nCTEQ and results with EPS09 and DSSZ is observed in nuclear modifications of both rapidity and $p_T$ distributions of $Z^0$ and $W$ in the future HIC.Comment: 13 pages, 21 figures, version accepted for publication in Eur. Phys. J.

Chaos game representation for comparison of whole genomes

BACKGROUND: Chaos game representation of genome sequences has been used for visual representation of genome sequence patterns as well as alignment-free comparisons of sequences based on oligonucleotide frequencies. However the potential of this representation for making alignment-based comparisons of whole genome sequences has not been exploited. RESULTS: We present here a fast algorithm for identifying all local alignments between two long DNA sequences using the sequence information contained in CGR points. The local alignments can be depicted graphically in a dot-matrix plot or in text form, and the significant similarities and differences between the two sequences can be identified. We demonstrate the method through comparison of whole genomes of several microbial species. Given two closely related genomes we generate information on mismatches, insertions, deletions and shuffles that differentiate the two genomes. CONCLUSION: Addition of the possibility of large scale sequence alignment to the repertoire of alignment-free sequence analysis applications of chaos game representation, positions CGR as a powerful sequence analysis tool

Real-time correlators in warped AdS/CFT correspondence

We study real-time correlators in the warped AdS/CFT correspondence. We apply the prescription used in the usual AdS/CFT correspondence and obtain the retarded Green's functions for the scalar and vector fields in the spacelike warped and the null warped black hole backgrounds. We find that the retarded Green's functions and the cross sections are well consistent with the predictions from dual CFT. Our results not only support strongly the conjectured warped AdS/CFT correspondence, but also show that the usual relativistic AdS/CFT prescription of obtaining the real-time correlators remain effective in more general backgrounds with anisotropic conformal infinity.Comment: 27 page

Motif-All: discovering all phosphorylation motifs

Background: Phosphorylation motifs represent common patterns around the phosphorylation site. The discovery of such kinds of motifs reveals the underlying regulation mechanism and facilitates the prediction of unknown phosphorylation event. To date, people have gathered large amounts of phosphorylation data, making it possible to perform substrate-driven motif discovery using data mining techniques. Results: We describe an algorithm called Motif-All that is able to efficiently identify all statistically significant motifs. The proposed method explores a support constraint to reduce search space and avoid generating random artifacts. As the number of phosphorylated peptides are far less than that of unphosphorylated ones, we divide the mining process into two stages: The first step generates candidates from the set of phosphorylated sequences using only support constraint and the second step tests the statistical significance of each candidate using the odds ratio derived from the whole data set. Experimental results on real data show that Motif-All outperforms current algorithms in terms of both effectiveness and efficiency. Conclusions: Motif-All is a useful tool for discovering statistically significant phosphorylation motifs. Source codes and data sets are available at: http://bioinformatics.ust.hk/MotifAll.rar

Reduced Levels of Membrane-Bound Alkaline Phosphatase Are Common to Lepidopteran Strains Resistant to Cry Toxins from Bacillus thuringiensis

Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Identification of biomarkers would assist in the development of sensitive DNA-based methods to monitor evolution of resistance to Bt toxins in natural populations. We report on the proteomic and genomic detection of reduced levels of midgut membrane-bound alkaline phosphatase (mALP) as a common feature in strains of Cry-resistant Heliothis virescens, Helicoverpa armigera and Spodoptera frugiperda when compared to susceptible larvae. Reduced levels of H. virescens mALP protein (HvmALP) were detected by two dimensional differential in-gel electrophoresis (2D-DIGE) analysis in Cry-resistant compared to susceptible larvae, further supported by alkaline phosphatase activity assays and Western blotting. Through quantitative real-time polymerase chain reaction (qRT-PCR) we demonstrate that the reduction in HvmALP protein levels in resistant larvae are the result of reduced transcript amounts. Similar reductions in ALP activity and mALP transcript levels were also detected for a Cry1Ac-resistant strain of H. armigera and field-derived strains of S. frugiperda resistant to Cry1Fa. Considering the unique resistance and cross-resistance phenotypes of the insect strains used in this work, our data suggest that reduced mALP expression should be targeted for development of effective biomarkers for resistance to Cry toxins in lepidopteran pests

Atomic Force Mechanobiology of Pluripotent Stem Cell-Derived Cardiomyocytes

We describe a method using atomic force microscopy (AFM) to quantify the mechanobiological properties of pluripotent, stem cell-derived cardiomyocytes, including contraction force, rate, duration, and cellular elasticity. We measured beats from cardiomyocytes derived from induced pluripotent stem cells of healthy subjects and those with dilated cardiomyopathy, and from embryonic stem cell lines. We found that our AFM method could quantitate beat forces of single cells and clusters of cardiomyocytes. We demonstrate the dose-responsive, inotropic effect of norepinephrine and beta-adrenergic blockade of metoprolol. Cardiomyocytes derived from subjects with dilated cardiomyopathy showed decreased force and decreased cellular elasticity compared to controls. This AFM-based method can serve as a screening tool for the development of cardiac-active pharmacological agents, or as a platform for studying cardiomyocyte biology

An association between unrecognized gastroesophageal reflux disease and excessive daytime sleepiness in Taiwanese subjects suspected to have liver disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>In traditional Chinese culture, liver disease is believed to underlie excessive daytime sleepiness (EDS). Consequently, Chinese patients with complaints of EDS and physicians who treat them suspect that a liver abnormality is present. If liver disease is ruled out, these patients are often discharged without treatment. Gastroesophageal reflux disease (GERD) is a common disorder also associated with EDS. This pilot study was undertaken to determine the prevalence of GERD among Taiwanese patients with complaints of EDS suspected to be related to liver disease but in whom no evidence for the latter was found.</p> <p>Methods</p> <p>From July 2009 to December 2009, 121 outpatients who presented to or were referred to the Department of Gastroenterology and Hepatology of the Chiayi Gung Memorial Hospital for evaluation of a complaint of EDS thought to be due to liver disease were examined. Demographic data were collected, and physical examinations and liver function tests were performed. Forty-eight patients had liver disease and were excluded. The Chinese Epworth Sleepiness Scale questionnaire (Chinese ESS) and the Chinese Gastroesophageal Reflux Disease Questionnaire (CGERDQ) were then administered to 73 included patients.</p> <p>Results</p> <p>More than half (56.2%) of the included patients were found to suffer from GERD. Patients with symptoms of GERD had higher mean CGERDQ scores than patients without symptoms of the disorder (18.88 ± 5.49 and 5.56 ± 3.57, respectively; <it>P </it>< 0.001). Patients with symptoms of GERD also had higher mean Chinese ESS scores than patients without symptoms (8.80 ± 5.49 and 3.13 ± 3.50, respectively; <it>P </it>< 0.001). Chinese ESS scores indicative of EDS were observed in 48.8% of patients with symptoms of GERD and in 3.1% of those without symptoms (<it>P </it>< 0.001). Differences between the two groups retained their significance after controlling for potential confounders.</p> <p>Conclusions</p> <p>A significant percentage of Taiwanese patients who complained of EDS and were admitted to our Hepatology/Gastroenterology Department due to a suspicion of liver disease actually had symptoms of GERD. Further studies are needed to ascertain whether treatment of GERD will effectively resolve EDS in these patients.</p