607 research outputs found

    Brita Lavada – An eco-efficient decorative mortar from Madeira Island

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    Brita lavada (washed gravel, in direct translation) is a decorative coating technology with a mortar based on cement, local Madeira basalt gravel and black pigment, currently used for masonry rendering on 20th-21st century Madeiran built heritage simulating stone masonry or cladding. Comparison of Brita Lavada and other cement based coating mortars was made regarding physical behaviour. The Brita Lavada shows high mechanical strength, acceptable water absorption and good water vapour permeability, what can justify its good durability on site and continuous application. The previous justify the interest on preserving the technology and is an example of optimised used of a local material, in the case a very hard basalt, with no possibility to be used for stonework, as a specific resource for a traditional, durable, eco-efficient decorative coating

    Responsible chain management: a capability assessment framework

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    In recent years, increased attention has been paid to issues of responsibility across the entire product lifecycle. Responsible behaviour of organizations in the product chain is dependent on the actions of other parties such as suppliers and customers. Only through co-operation and close interaction between the different parties involved is it possible to come to a specified form of responsible chain management. Drawing on stakeholder theory and literature on the resource-based view of the firm, this article presents a framework for assessing the organizational capabilities of responding to claims from internal and external parties. Interpretations of stakeholder interests, integration into business processes, monitoring these processes, and communication with stakeholders are the central processes in this framework. The application of this framework to three cases of responsible chain management illustrates the functioning of the framework as a tool for assessing organizational capabilities

    The devil is in the detail:tobacco industry political influence in the Dutch implementation of the 2001 EU Tobacco Products Directive

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    Introduction - The Dutch implementation of the black border provision in the 2001 European Union Tobacco Products Directive (TPD) is studied to examine the implications of tobacco industry involvement in the implementation phase of the policy process. Methods - A qualitative analysis was conducted of Dutch government documents obtained through Freedom of Information Act requests, triangulated with in-depth interviews with key informants and secondary data sources (publicly available government documents, scientific literature, and news articles). Results - Tobacco manufacturers’ associations were given the opportunity to set implementation specifications via a fast-track deal with the government. The offer of early implementation of the labelling section of the TPD was used as political leverage by the industry, and underpinned by threats of litigation and arguments highlighting the risks of additional public costs and the benefits to the government of expediency and speed. Ultimately, the government agreed to the industry's interpretation, against the advice of the European Commission. Conclusions - The findings highlight the policy risks associated with corporate actors’ ability to use interactions over technical product specifications to influence the implementation of health policy and illustrate the difficulties in limiting industry interference in accordance with Article 5.3 of the Framework Convention on Tobacco Control (FCTC). The implementation phase is particularly vulnerable to industry influence, where negotiation with industry actors may be unavoidable and the practical implications of relatively technical considerations are not always apparent to policymakers. During the implementation of the new TPD 2014/40/EU, government officials are advised to take a proactive role in stipulating technical specifications

    Scaling of cardiac morphology is interrupted by birth in the developing sheep Ovis aries.

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    Scaling of the heart across development can reveal the degree to which variation in cardiac morphology depends on body mass. In this study, we assessed the scaling of heart mass, left and right ventricular masses, and ventricular mass ratio, as a function of eviscerated body mass across fetal and postnatal development in Horro sheep Ovis aries (~50-fold body mass range; N = 21). Whole hearts were extracted from carcasses, cleaned, dissected into chambers and weighed. We found a biphasic relationship when heart mass was scaled against body mass, with a conspicuous 'breakpoint' around the time of birth, manifest not by a change in the scaling exponent (slope), but rather a jump in the elevation. Fetal heart mass (g) increased with eviscerated body mass (Mb , kg) according to the power equation 4.90 Mb0.88 ± 0.26 (± 95%CI) , whereas postnatal heart mass increased according to 10.0 Mb0.88 ± 0.10 . While the fetal and postnatal scaling exponents are identical (0.88) and reveal a clear dependence of heart mass on body mass, only the postnatal exponent is significantly less than 1.0, indicating the postnatal heart becomes a smaller component of body mass as the body grows, which is a pattern found frequently with postnatal cardiac development among mammals. The rapid doubling in heart mass around the time of birth is independent of any increase in body mass and is consistent with the normalization of wall stress in response to abrupt changes in volume loading and pressure loading at parturition. We discuss variation in scaling patterns of heart mass across development among mammals, and suggest that the variation results from a complex interplay between hard-wired genetics and epigenetic influences

    Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

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    A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

    How much do health care providers value a community-based asthma care program? – a survey to collect their opinions on the utilities of and barriers to its uptake

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    <p>Abstract</p> <p>Background</p> <p>A comprehensive asthma care program (ACP) based on Canadian Asthma Consensus Guidelines was implemented in 8 primary care sites in Ontario, Canada. A survey was distributed to health care providers' (HCPs) to collect their opinions on the utilities of and barriers to the uptake of the ACP.</p> <p>Methods</p> <p>A 39-item self-administered survey was mailed to 184 HCPs and support staff involved in delivering the ACP at the end of implementation. The items were presented in mixed formats with most items requiring responses on a five-point Likert scale. Distributions of responses were analyzed and compared across types of HCPs and sites.</p> <p>Results</p> <p>Of the 184 surveys distributed, 108 (59%) were returned, and of that, 83 were completed by HCPs who had clinical contact with the patients. Overall, 95% of the HCPs considered the ACP useful for improving asthma care management. Most HCPs favored using the asthma care map (72%), believed it decreased uncertainties and variations in patient management (91%), and considered it a convenient and reliable source of information (86%). The most commonly reported barrier was time required to complete the asthma care map. Over half of the HCPs reported challenges to using spirometry, while almost 40% identified barriers to using the asthma action plan.</p> <p>Conclusion</p> <p>Contrary to the notion that physicians believe that guidelines foster cookbook medicine, our study showed that HCPs believed that the ACP offered an effective and reliable approach for enhancing asthma care and management in primary care.</p

    Dynamics of the Acetylcholinesterase Tetramer

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    Acetylcholinesterase rapidly hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses, including the neuromuscular junction. The tetramer is the most important functional form of the enzyme. Two low-resolution crystal structures have been solved. One is compact with two of its four peripheral anionic sites (PAS) sterically blocked by complementary subunits. The other is a loose tetramer with all four subunits accessible to solvent. These structures lacked the C-terminal amphipathic t-peptide (WAT domain) that interacts with the proline-rich attachment domain (PRAD). A complete tetramer model (AChEt) was built based on the structure of the PRAD/WAT complex and the compact tetramer. Normal mode analysis suggested that AChEt could exist in several conformations with subunits fluctuating relative to one another. Here, a multiscale simulation involving all-atom molecular dynamics and Cα-based coarse-grained Brownian dynamics simulations was carried out to investigate the large-scale intersubunit dynamics in AChEt. We sampled the ns-μs timescale motions and found that the tetramer indeed constitutes a dynamic assembly of monomers. The intersubunit fluctuation is correlated with the occlusion of the PAS. Such motions of the subunits “gate” ligand-protein association. The gates are open more than 80% of the time on average, which suggests a small reduction in ligand-protein binding. Despite the limitations in the starting model and approximations inherent in coarse graining, these results are consistent with experiments which suggest that binding of a substrate to the PAS is only somewhat hindered by the association of the subunits

    Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to different agents of oxidative stress

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    Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress effects of reactive oxygen species. In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to the exposure to the ROSinducing agents’ paraquat, hydrogen peroxide, and increased air pressure was analyzed. Yeast cells at exponential phase were exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of 3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation was lower for the cells exposed to increased air pressure than for those exposed to chemical oxidants. The glutathione induction occurred only in Y. lipolytica strain and reached the highest level as a response to PQ exposure. In general, antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The enzyme superoxide dismutase was induced in both strains under all the oxidant conditions but was dependent on the cellular growth phase, being undetectable in non-growing cells, whereas glutathione reductase was more induced in those conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both yeast cultures underwent no cellular growth inhibition with increased air pressure, indicating that these yeast species were able to adapt to the oxidative stressful environment.The authors acknowledge the financial support provided by "Fundacao para a Ciencia e Tecnologia" (Grant SFRH/BD/47371/2008)

    Evidence of Differential Allelic Effects between Adolescents and Adults for Plasma High-Density Lipoprotein

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    A recent meta-analysis of genome-wide association (GWA) studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25–30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C) and triglycerides vary with age. We studied Australian adults (N = 10,151) and adolescents (N = 2,363) who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (pHet<0.05 at 5 out of 37 loci), but no more than expected by chance for LDL-C (1 out of 14 loci), or trigycerides (0 out 24). There were 2 (out of 5) with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021±0.033 mmol/L) and adults (0.157±0.023 mmol/L), pHet = 0.013; followed by ZNF664 (pHet = 0.018) and PABPC4 (pHet = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults

    Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

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    Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12–1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02–1.27] and 1.21 [95 % CI 1.07–1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity
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