306 research outputs found

    An analysis of consumer protection for gamblers across different online gambling operators in Ireland: a descriptive study

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    The aim of the present study was to evaluate the responsible gambling tools which are available to online gamblers at Irish online gambling websites. The present study used a similar methodology to a recent study carried out on the world’s most popular websites (Bonello and Griffiths Gaming Law Review and Economics, 21, 278–285, 2017), where 50 of the most advertised online gambling websites were evaluated in relation to their responsible gambling (RG) practices. The present study evaluated 39 gambling websites with either a “.ie” or “.com/ie” domain. Each website was evaluated by checking for a number of RG practices, including presence of a dedicated RG page; age verification; access to gambling account history; the availability of RG tools, such as limit setting facilities and exclusion settings; and links to limit-setting options on the deposit page. Descriptive statistics were then performed on the results from each website. Of the 39 online gambling operators identified, 22 redirected gamblers to a “.com” domain, while 17 operators remained as a “.ie” domain. Thirty-five websites (89.7%) visited had a dedicated RG page. Responsible gambling features were evaluated and demonstrated to be available in an inconsistent manner across online gambling websites. Irish websites were shown to perform poorly in comparison with non-Irish counterparts in the provision of RG tools. The researchers of the present study are not aware of any similar studies conducted to date in Ireland

    The furan microsolvation blind challenge for quantum chemical methods: First steps

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    © 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

    Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos

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    Circulating white blood cell (WBC) counts (neutrophils, monocytes, lymphocytes, eosinophils, basophils) differ by ethnicity. The genetic factors underlying basal WBC traits in Hispanics/Latinos are unknown. We performed a genome-wide association study of total WBC and differential counts in a large, ethnically diverse US population sample of Hispanics/Latinos ascertained by the Hispanic Community Health Study and Study of Latinos (HCHS/SOL). We demonstrate that several previously known WBC-associated genetic loci (e.g. the African Duffy antigen receptor for chemokines null variant for neutrophil count) are generalizable to WBC traits in Hispanics/Latinos. We identified and replicated common and rare germ-line variants at FLT3 (a gene often somatically mutated in leukemia) associated with monocyte count. The common FLT3 variant rs76428106 has a large allele frequency differential between African and non-African populations. We also identified several novel genetic loci involving or regulating hematopoietic transcription factors (CEBPE-SLC7A7, CEBPA and CRBN-TRNT1) associated with basophil count. The minor allele of the CEBPE variant associated with lower basophil count has been previously associated with Amerindian ancestry and higher risk of acute lymphoblastic leukemia in Hispanics. Together, these data suggest that germline genetic variation affecting transcriptional and signaling pathways that underlie WBC development and lineage specification can contribute to inter-individual as well as ethnic differences in peripheral blood cell counts (normal hematopoiesis) in addition to susceptibility to leukemia (malignant hematopoiesis)

    The first microsolvation step for furans : new experiments and benchmarking strategies

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    The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight

    Local sequence alignments statistics: deviations from Gumbel statistics in the rare-event tail

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    <p>Abstract</p> <p>Background</p> <p>The optimal score for ungapped local alignments of infinitely long random sequences is known to follow a Gumbel extreme value distribution. Less is known about the important case, where gaps are allowed. For this case, the distribution is only known empirically in the high-probability region, which is biologically less relevant.</p> <p>Results</p> <p>We provide a method to obtain numerically the biologically relevant rare-event tail of the distribution. The method, which has been outlined in an earlier work, is based on generating the sequences with a parametrized probability distribution, which is biased with respect to the original biological one, in the framework of Metropolis Coupled Markov Chain Monte Carlo. Here, we first present the approach in detail and evaluate the convergence of the algorithm by considering a simple test case. In the earlier work, the method was just applied to one single example case. Therefore, we consider here a large set of parameters:</p> <p>We study the distributions for protein alignment with different substitution matrices (BLOSUM62 and PAM250) and affine gap costs with different parameter values. In the logarithmic phase (large gap costs) it was previously assumed that the Gumbel form still holds, hence the Gumbel distribution is usually used when evaluating p-values in databases. Here we show that for all cases, provided that the sequences are not too long (<it>L </it>> 400), a "modified" Gumbel distribution, i.e. a Gumbel distribution with an additional Gaussian factor is suitable to describe the data. We also provide a "scaling analysis" of the parameters used in the modified Gumbel distribution. Furthermore, via a comparison with BLAST parameters, we show that significance estimations change considerably when using the true distributions as presented here. Finally, we study also the distribution of the sum statistics of the <it>k </it>best alignments.</p> <p>Conclusion</p> <p>Our results show that the statistics of gapped and ungapped local alignments deviates significantly from Gumbel in the rare-event tail. We provide a Gaussian correction to the distribution and an analysis of its scaling behavior for several different scoring parameter sets, which are commonly used to search protein data bases. The case of sum statistics of <it>k </it>best alignments is included.</p

    Separate Origins of Group I Introns in Two Mitochondrial Genes of the Katablepharid Leucocryptos marina

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    Mitochondria are descendants of the endosymbiotic α-proteobacterium most likely engulfed by the ancestral eukaryotic cells, and the proto-mitochondrial genome should have been severely streamlined in terms of both genome size and gene repertoire. In addition, mitochondrial (mt) sequence data indicated that frequent intron gain/loss events contributed to shaping the modern mt genome organizations, resulting in the homologous introns being shared between two distantly related mt genomes. Unfortunately, the bulk of mt sequence data currently available are of phylogenetically restricted lineages, i.e., metazoans, fungi, and land plants, and are insufficient to elucidate the entire picture of intron evolution in mt genomes. In this work, we sequenced a 12 kbp-fragment of the mt genome of the katablepharid Leucocryptos marina. Among nine protein-coding genes included in the mt genome fragment, the genes encoding cytochrome b and cytochrome c oxidase subunit I (cob and cox1) were interrupted by group I introns. We further identified that the cob and cox1 introns host open reading frames for homing endonucleases (HEs) belonging to distantly related superfamilies. Phylogenetic analyses recovered an affinity between the HE in the Leucocryptos cob intron and two green algal HEs, and that between the HE in the Leucocryptos cox1 intron and a fungal HE, suggesting that the Leucocryptos cob and cox1 introns possess distinct evolutionary origins. Although the current intron (and intronic HE) data are insufficient to infer how the homologous introns were distributed to distantly related mt genomes, the results presented here successfully expanded the evolutionary dynamism of group I introns in mt genomes

    Mosaic Chromosomal alterations in Blood across ancestries Using Whole-Genome Sequencing

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    Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis

    Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

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    BACKGROUND: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. METHODS: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. RESULTS: We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. CONCLUSION: We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability
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