1,194 research outputs found
The Grey Web: dataveillance vision fulfilled through the evolving Web
No full textOver the past three decades, Web has evolved from an information medium to an intricate economic ecosystem. Initially focused on supporting the transition from traditional business practices to e-commerce, the Web has given rise to new, purely Web based businesses. Aligned with the original vision and expectations of the ‘free Web’, they have provided free services but, over time, developed business models that leverage the user digital footprints and the user generated content to create economic value. With the use of computing technologies to analyze, aggregate, and share such data, individuals’ privacy has been undermined and, with that, the their ability to shape their role in the digital society and beyond. The purpose of this paper is to instigate the dialogue around the critical societal issues that arise from the current Web economy and motivate research initiatives to assist with addressing them. We present three case studies that quantify the extent, rate, and pervasiveness of the user tracking on the Web. We use them to illustrate the determining aspects of the Web that have to be taken into account by the Web Science community. As researchers we aspire to understand the nature of the Web in depth and, based on that, propose designs and policies that are required to ensure that the Web is fit to be the underpinning of our societies and our digital future
Developing the formal structures of artistic practice-as-research
No full textIn this article I discuss a topic that is emerging as a valuable paradigm for creative practitioners - practice-as-research. There is some controversy over this term that, I believe, goes to the heart of our understanding of the nature of knowledge. The controversy relates to the idea that practice and research are two inherently different types of activity and therefore that it impossible to engage in one ‘as’ the other. Tim Ingold’s (2011) work on the anthropology of knowledge and skill alongside a broader stream of work on cognition and perception (see for example Lakoff & Johnson 2003 and Gibson 1979) suggests that both artistic practice and academic research involve ‘puzzle-solving… carried on within the context of involvement in a real world of persons, objects and relations.’ (Ingold 2011, p.419). The argument revolves around the notion that there is no such thing as disembodied or abstract knowledge and that all knowledge is both embodied and personally related to the world one inhabits. As such, the written word provides a schematic system for representing the much richer communication processes of speech and bodily experience. The written word, however, can only be understood through reference to our lived experience. Lave (1990, p.310) has termed this ‘understanding in practice’ as a knowledge ‘based on rich expectations generated over time about its shape’ (Lave 1990, p.323). Scholarly research outputs and their modes of publication are still firmly entrenched in the printed word. I will explore strategies for communicating the non-verbal knowledge that forms the basis of much practice-as-research
Unraveling the directional link between adiposity and inflammation: a bidirectional mendelian randomization approach
No full text<b>Context</b>: Associations between adiposity and circulating inflammation markers are assumed to be causal, although the direction of the relationship has not been proven.
<b>Objective</b>: The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian randomization approach.
<b>Methods</b>: In the PROSPER study of 5804 elderly patients, we related C-reactive protein (CRP) single nucleotide polymorphisms (SNPs) (rs1800947 and rs1205) and adiposity SNPs (FTO and MC4R) to body mass index (BMI) as well as circulating levels of CRP and leptin. We gave each individual two allele scores ranging from zero to 4, counting each pair of alleles related to CRP levels or BMI.
<b>Results</b>: With increasing CRP allele score, there was a stepwise decrease in CRP levels (P for trend < 0.0001) and a 1.98 mg/liter difference between extremes of the allele score distribution, but there was no associated change in BMI or leptin levels (P ≥ 0.89). By contrast, adiposity allele score was associated with 1) an increase in BMI (1.2 kg/m2 difference between extremes; P for trend 0.002); 2) an increase in circulating leptin (5.77 ng/ml difference between extremes; P for trend 0.0027); and 3) increased CRP levels (1.24 mg/liter difference between extremes; P for trend 0.002).
<b>Conclusions</b>: Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels, with no evidence for any reverse pathway. Future studies should extend our findings to other circulating inflammatory parameters. This study illustrates the potential power of Mendelian randomization to dissect directions of causality between intercorrelated metabolic factors
Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans
No full textBackground: the APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods: we genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results: the APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). Conclusions: this is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
No full textThere is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
Research in Art and Design (Royal College of Art Research Papers, Vol 1, No 1, 1993/4)
No full textAn exploration of the nature of research in art and design. What constitutes research in these fields and how does it differ from practice-led art and design? The author also considers the prevailing and misleading stereotypes of the researcher which distract us from the true nature of the task
Effects of the diabetes linked TCF7L2 polymorphism in a representative older population.
No full textAssessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach
No full textRecent evidence supports the strong overlap between genes implicated in monogenic diabetes and susceptibility to type 2 diabetes. Transient neonatal diabetes mellitus (TNDM) is a rare disorder associated with overexpression of genes at a paternally expressed imprinted locus on chromosome 6q24. There are two overlapping genes in this region: the transcription factor zinc finger protein associated with cell cycle control and apoptosis (ZAC also known as PLAGL1) and HYMA1, which encodes an untranslated mRNA. Several type 2 diabetes linkage studies have reported linkage to chromosome 6q22-25. We hypothesized that common genetic variation at this TNDM region influences type 2 diabetes susceptibility. In addition to the coding regions, we used comparative genomic analysis to identify conserved noncoding regions, which were resequenced for single nucleotide polymorphism (SNP) discovery in 47 individuals. Twenty-six SNPs were identified. Fifteen tag SNPs (tSNPs) were successfully genotyped in a large case-control (n = 3,594) and family-based (n = 1,654) study. We did not find any evidence of association or overtransmission of any tSNP to affected offspring or of a parent-of-origin effect. Using a study sufficiently powered to detect odds ratios of <1.2, we conclude that common variation in the TNDM region does not play an important role in the genetic susceptibility to type 2 diabetes.<br/
Physiology helps GWAS take a step closer to mechanism
No full textPublishedCommentJournal ArticleGenome-wide association studies (GWAS) have been extremely successful at identifying replicable associations between common genetic variants and type 2 diabetes risk. The latest studies, including 35,000 European, 7,000 East Asian, 5,500 South Asian, and most recently 3,800 Latin American and 6,000 Japanese type 2 diabetes cases, bring the total number of associated variants to more than 70. There is strong evidence that many of the associated genetic variants lie in or close to genes important in type 2 diabetes etiology (e.g., the regions of the genome identified by GWAS are enriched for monogenic diabetes genes, such as HNF1A, HNF1B, and PPARG, and small noncoding regions of the genome [enhancers] critical for islet-specific gene expression). Nevertheless, the field has not moved from genetic associations to improved understanding of biology as quickly or as often as hoped
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