185 research outputs found

    Appointing Women to Boards: Is There a Cultural Bias?

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    Companies that are serious about corporate governance and business ethics are turning their attention to gender diversity at the most senior levels of business (Institute of Business Ethics, Business Ethics Briefing 21:1, 2011). Board gender diversity has been the subject of several studies carried out by international organizations such as Catalyst (Increasing gender diversity on boards: Current index of formal approaches, 2012), the World Economic Forum (Hausmann et al., The global gender gap report, 2010), and the European Board Diversity Analysis (Is it getting easier to find women on European boards? 2010). They all lead to reports confirming the overall relatively low proportion of women on boards and the slow pace at which more women are being appointed. Furthermore, the proportion of women on corporate boards varies much across countries. Based on institutional theory, this study hypothesizes and tests whether this variation can be attributed to differences in cultural settings across countries. Our analysis of the representation of women on boards for 32 countries during 2010 reveals that two cultural characteristics are indeed associated with the observed differences. We use the cultural dimensions proposed by Hofstede (Culture’s consequences: International differences in work-related values, 1980) to measure this construct. Results show that countries which have the greatest tolerance for inequalities in the distribution of power and those that tend to value the role of men generally exhibit lower representations of women on boards

    A cross sectional evaluation of a total smoking ban at a large Australian university

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    Background: Total smoking bans have been found to contribute positively to the health of non-smokers by reducing exposure to second-hand smoke, and to enhance the likelihood of cessation among smokers. Methods: Two cross-sectional electronic surveys of staff and students at a large Australian university were conducted prior (n = 969) and 1 year post (n = 670) the implementation of a smoke free campus policy. Demographics, tobacco use, intention to quit, attitudes towards smoking and smoking restrictions and awareness of and attitudes towards the campus smoking policy were measured. Results: Exposure to second-hand smoke (SHS) reduced significantly (p < 0.001) one year after policy implementation. Smoking prevalence was similar at both time periods (T1 9.3 %; T2 8.4 %) and over half of smokers indicated they were planning to quit smoking in the future (T1 65.5 vs T2 62.3 %). There was a significant increase in positive responses to the statement the campus should be totally smoke free including all outdoor areas at T2 compared to T1 (T1 60.8 vs T2 71.4 %; p < 0.001), however respondents felt there should be places on campus for smokers to smoke (T1 53.6 vs T2 47 %; p < 0.05). Conclusions: This study found a significant positive difference in exposure SHS after implementation of the total ban. Although prevalence of smoking in this study was low, the proportion of respondents who were contemplating smoking cessation suggests support for smokers would be beneficial. Continued awareness raising, education and enforcement is likely to enhance the long term outcomes of the total ban

    Identification of Domains and Amino Acids Essential to the Collagen Galactosyltransferase Activity of GLT25D1

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    Collagen is modified by hydroxylation and glycosylation of hydroxylysine residues. This glycosylation is initiated by the β1,O galactosyltransferases GLT25D1 and GLT25D2. The structurally similar protein cerebral endothelial cell adhesion molecule CEECAM1 was previously reported to be inactive when assayed for collagen glycosyltransferase activity. To address the cause of the absent galactosyltransferase activity, we have generated several chimeric constructs between the active human GLT25D1 and inactive human CEECAM1 proteins. The assay of these chimeric constructs pointed to a short central region and a large C-terminal region of CEECAM1 leading to the loss of collagen galactosyltransferase activity. Examination of the three DXD motifs of the active GLT25D1 by site-directed mutagenesis confirmed the importance of the first (amino acids 166–168) and second motif (amino acids 461–463) for enzymatic activity, whereas the third one was dispensable. Since the second DXD motif is incomplete in CEECAM1, we have restored the motif by introducing the substitution S461D. This change did not restore the activity of the C-terminal region, thereby showing that additional amino acids were required in this C-terminal region to confer enzymatic activity. Finally, we have introduced the substitution Q471R-V472M-N473Q-P474V in the CEECAM1-C-terminal construct, which is found in most animal GLT25D1 and GLT25D2 isoforms but not in CEECAM1. This substitution was shown to partially restore collagen galactosyltransferase activity, underlining its importance for catalytic activity in the C-terminal domain. Because multiple mutations in different regions of CEECAM1 contribute to the lack of galactosyltransferase activity, we deduced that CEECAM1 is functionally different from the related GLT25D1 protein

    Bibliometric Evidence for a Hierarchy of the Sciences

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    The hypothesis of a Hierarchy of the Sciences, first formulated in the 19(th) century, predicts that, moving from simple and general phenomena (e.g. particle dynamics) to complex and particular (e.g. human behaviour), researchers lose ability to reach theoretical and methodological consensus. This hypothesis places each field of research along a continuum of complexity and "softness", with profound implications for our understanding of scientific knowledge. Today, however, the idea is still unproven and philosophically overlooked, too often confused with simplistic dichotomies that contrast natural and social sciences, or science and the humanities. Empirical tests of the hypothesis have usually compared few fields and this, combined with other limitations, makes their results contradictory and inconclusive. We verified whether discipline characteristics reflect a hierarchy, a dichotomy or neither, by sampling nearly 29,000 papers published contemporaneously in 12 disciplines and measuring a set of parameters hypothesised to reflect theoretical and methodological consensus. The biological sciences had in most cases intermediate values between the physical and the social, with bio-molecular disciplines appearing harder than zoology, botany or ecology. In multivariable analyses, most of these parameters were independent predictors of the hierarchy, even when mathematics and the humanities were included. These results support a "gradualist" view of scientific knowledge, suggesting that the Hierarchy of the Sciences provides the best rational framework to understand disciplines' diversity. A deeper grasp of the relationship between subject matter's complexity and consensus could have profound implications for how we interpret, publish, popularize and administer scientific research

    "May I Buy a Pack of Marlboros, Please?" A Systematic Review of Evidence to Improve the Validity and Impact of Youth Undercover Buy Inspections

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    Most smokers become addicted to tobacco products before they are legally able to pur- chase these products. We systematically reviewed the literature on protocols to assess underage purchase and their ecological validity. We conducted a systematic search in May 2015 in PubMed and PsycINFO. We independently screened records for inclusion. We con- ducted a narrative review and examined implications of two types of legal authority for proto- cols that govern underage buy enforcement in the United States: criminal (state-level laws prohibiting sales to youth) and administrative (federal regulations prohibiting sales to youth). Ten studies experimentally assessed underage buy protocols and 44 studies assessed the association between youth characteristics and tobacco sales. Protocols that mimicked real-world youth behaviors were consistently associated with substantially greater likelihood of a sale to a youth. Many of the tested protocols appear to be designed for compliance with criminal law rather than administrative enforcement in ways that limited ecological validity. This may be due to concerns about entrapment. For administrative enforcement in particular, entrapment may be less of an issue than commonly thought. Commonly used underage buy protocols poorly represent the reality of youths' access to tobacco from retailers. Compliance check programs should allow youth to present them- selves naturally and attempt to match the community’s demographic makeup

    Magnesium Limitation Is an Environmental Trigger of the Pseudomonas aeruginosa Biofilm Lifestyle

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    Biofilm formation is a conserved strategy for long-term bacterial survival in nature and during infections. Biofilms are multicellular aggregates of cells enmeshed in an extracellular matrix. The RetS, GacS and LadS sensors control the switch from a planktonic to a biofilm mode of growth in Pseudomonas aeruginosa. Here we detail our approach to identify environmental triggers of biofilm formation by investigating environmental conditions that repress expression of the biofilm repressor RetS. Mg2+ limitation repressed the expression of retS leading to increased aggregation, exopolysaccharide (EPS) production and biofilm formation. Repression of retS expression under Mg2+ limitation corresponded with induced expression of the GacA-controlled small regulatory RNAs rsmZ and rsmY and the EPS biosynthesis operons pel and psl. We recently demonstrated that extracellular DNA sequesters Mg2+ cations and activates the cation-sensing PhoPQ two-component system, which leads to increased antimicrobial peptide resistance in biofilms. Here we show that exogenous DNA and EDTA, through their ability to chelate Mg2+, promoted biofilm formation. The repression of retS in low Mg2+ was directly controlled by PhoPQ. PhoP also directly controlled expression of rsmZ but not rsmY suggesting that PhoPQ controls the equilibrium of the small regulatory RNAs and thus fine-tunes the expression of genes in the RetS pathway. In summary, Mg2+ limitation is a biologically relevant environmental condition and the first bonafide environmental signal identified that results in transcriptional repression of retS and promotes P. aeruginosa biofilm formation

    First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

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    BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

    Differential Carbohydrate Recognition by Campylobacter jejuni Strain 11168: Influences of Temperature and Growth Conditions

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    The pathogenic clinical strain NCTC11168 was the first Campylobacter jejuni strain to be sequenced and has been a widely used laboratory model for studying C. jejuni pathogenesis. However, continuous passaging of C. jejuni NCTC11168 has been shown to dramatically affect its colonisation potential. Glycan array analysis was performed on C. jejuni NCTC11168 using the frequently passaged, non-colonising, genome sequenced (11168-GS) and the infrequently passaged, original, virulent (11168-O) isolates grown or maintained under various conditions. Glycan structures recognised and bound by C. jejuni included terminal mannose, N-acetylneuraminic acid, galactose and fucose. Significantly, it was found that only when challenged with normal oxygen at room temperature did 11168-O consistently bind to sialic acid or terminal mannose structures, while 11168-GS bound these structures regardless of growth/maintenance conditions. Further, binding of un-capped galactose and fucosylated structures was significantly reduced when C. jejuni was maintained at 25°C under atmospheric oxygen conditions. These binding differences identified through glycan array analysis were confirmed by the ability of specific lectins to competitively inhibit the adherence of C. jejuni to a Caco-2 intestinal cell line. Our data suggests that the binding of mannose and/or N-acetylneuraminic acid may provide the initial interactions important for colonisation following environmental exposure

    Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model

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    Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been observed to impact renal function in gene-deficient patients and may play a role in the adverse side effects observed in clinical trials. Genetic risk factors for drug treatment were also predicted that correspond to both characterized and unknown renal metabolic disorders as well as cryptic genetic deficiencies that are not expected to exhibit a renal disorder phenotype except under drug treatment. This study represents a novel integration of structural and systems biology and a first step towards computational systems medicine. The methodology introduced herein has important implications for drug development and personalized medicine
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