163 resultados para Hansen, Lars
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Reflective thinking is an important skill in psychology, both as a tool in the therapeutic process and in professional development. The adapted 4Rs Model provides reflective writing structure and highlights the importance of Reporting & Responding, Relating, Reasoning and Reconstructing to students who are new to writing reflections. This chapter presents a case in which the 4Rs model (modified from the 5Rs model in Chap. 2 of this edition) was adopted to support reflective writing skills of undergraduate psychology students in a first year unit and in a final year unit. Although all students reflected on their learning within the units, the support activities leading up to the reflective tasks were adjusted to account for differences in the abilities of the cohorts and the focus of the units. In an evaluation survey, both groups of students endorsed statements about the importance of reflections and the utility of using the model. First year students also reported some difficulties understanding the 4Rs. This chapter will explore how first and final year students can be supported to develop reflection skills through scaffolding and modification of the same approaches and model.
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This paper examines the feasibility of using vertical light pipes to naturally illuminate the central core of a multilevel building not reached by window light. The challenges addressed were finding a method to extract and distribute equal amounts of light at each level and designing collectors to improve the effectiveness of vertical light pipes in delivering low elevation sunlight to the interior. Extraction was achieved by inserting partially reflecting cones within transparent sections of the pipes at each floor level. Theory was formulated to estimate the partial reflectance necessary to provide equal light extraction at each level. Designs for daylight collectors formed from laser cut panels tilted above the light pipe were developed and the benefits and limitations of static collectors as opposed to collectors that follow the sun azimuth investigated. Performance was assessed with both basic and detailed mathematical simulation and by observations made with a five level model building under clear sky conditions.
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BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.
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Studies of semantic context effects in spoken word production have typically distinguished between categorical (or taxonomic) and associative relations. However, associates tend to confound semantic features or morphological representations, such as whole-part relations and compounds (e.g., BOAT-anchor, BEE-hive). Using a picture-word interference paradigm and functional magnetic resonance imaging (fMRI), we manipulated categorical (COW-rat) and thematic (COW-pasture) TARGET-distractor relations in a balanced design, finding interference and facilitation effects on naming latencies, respectively, as well as differential patterns of brain activation compared with an unrelated distractor condition. While both types of distractor relation activated the middle portion of the left middle temporal gyrus (MTG) consistent with retrieval of conceptual or lexical representations, categorical relations involved additional activation of posterior left MTG, consistent with retrieval of a lexical cohort. Thematic relations involved additional activation of the left angular gyrus. These results converge with recent lesion evidence implicating the left inferior parietal lobe in processing thematic relations and may indicate a potential role for this region during spoken word production.
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Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.
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The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study...
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Vertical windows are the most common and simplest method to introduce daylight to interior spaces of office buildings, while also providing a view and connection to the outside. However, high contrast ratios between windows and surrounding surfaces can cause visual discomfort for occupants and can negatively influence their health and productivity. Consequently, building occupants may try to adapt their working environment through closing blinds and turning on lights in order to improve indoor visual comfort. Such interventions defeat the purpose of daylight harvesting systems and can increase the forecast electric lighting consumption in buildings that include such systems. A simple strategy to prevent these problematic consequences is to reduce the luminance contrasts presented by the window wall by increasing the luminance of areas surrounding the window through the sparing use of energy-efficient supplementary lighting, such light emitting diodes (LEDs). This paper presents the result of a pilot study in typical office in Brisbane, Australia that tests the effectiveness of a supplementary LED lighting system. The study shows an improvement in the appraisal of the visual environment is achieved using the supplementary system, along with up to 88% reductions in luminance contrast at the window wall. Also observed is a 36% reduction in the likelihood of user interventions that would increase energy usage. These results are used as the basis of an annual energy simulation of the test office and indicate that supplementary systems could be used to save energy beyond what is typically realised in side lit office spaces.
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High contrast ratios between windows and surrounding surfaces could cause reduced visibility or discomfort for occupants. Consequently, building users may choose to intervene in lighting conditions through closing blinds and turning on the lamps in order to enhance indoor visual comfort. Such interventions increase projected electric lighting use in buildings. One simple method to prevent these problematic issues is increasing the luminance of the areas surrounding to the bright surface of windows through the use of energy-efficient supplementary lighting, such Light Emitting Diodes (LEDs). This paper reports on the results of a pilot study in conventional office in Brisbane, Australia. The outcomes of this study indicated that a supplementary LED system of approximately 18 W could reduce the luminance contrast on the window wall from values in the order of 117:1 to 33:1. In addition, the results of this experiment suggested that this supplementary strategy could increase the subjective scale appraisal of window appearance by approximately 33%, as well as reducing the likelihood of users’ intention to turn on the ceiling lights by about 27%. It could also diminish the likelihood of occupants’ intention to move the blind down by more than 90%.
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Personal and political action on climate change is traditionally thought to be motivated by people accepting its reality and importance. However, convincing the public that climate change is real faces powerful ideological obstacles1, 2, 3, 4, and climate change is slipping in public importance in many countries5, 6. Here we investigate a different approach, identifying whether potential co-benefits of addressing climate change7 could motivate pro-environmental behaviour around the world for both those convinced and unconvinced that climate change is real. We describe an integrated framework for assessing beliefs about co-benefits8, distinguishing social conditions (for example, economic development, reduced pollution or disease) and community character (for example, benevolence, competence). Data from all inhabited continents (24 countries; 6,196 participants) showed that two co-benefit types, Development (economic and scientific advancement) and Benevolence (a more moral and caring community), motivated public, private and financial actions to address climate change to a similar degree as believing climate change is important. Critically, relationships were similar for both convinced and unconvinced participants, showing that co-benefits can motivate action across ideological divides. These relationships were also independent of perceived climate change importance, and could not be explained by political ideology, age, or gender. Communicating co-benefits could motivate action on climate change where traditional approaches have stalled.
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Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.
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The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.
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Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.
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A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.