Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.

To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.Please refer to the manuscript or visit the publisher's website for funding infomation

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Undoing Churnalism? Users sharing local news on Facebook

This study investigates the types of information that users of a local news site share on Facebook. This issue relates to the idea of "churnalism", which concerns a form of weakened journalism that diminishes the ability to perform expected tasks in a democratic society. As a major social media platform, Facebook has acquired substantial influence over news dissemination, and therefore, scholarly focus needs to be directed to users as news disseminators. The manners by which users share news on Facebook indicate whether churnalism is promoted or abated through users' interaction with online news. In this study, a quantitative content analysis illustrates how 348 news articles published on a local news site were shared 7266 times. The results show that concerns related to churnalism should be directed primarily to the fact that the news outlet only rarely provides users with opportunities to interact with serious or hard news, while lightweight news is frequently offered. Despite this, users abate churnalism in the sense that the news they prefer to share is news from in-house sources rather than from external sources. The news extensively shared covers changes in the vicinity, and health care, and has emerged from local and regional events

Att leva med elöverkänslighet : åtgärder och hälsa

Godkänd; 1996; 20091126 (andbra)</p

Elevmedverkan i kvalitetsarbetet : - ett exempel angående hur en kursutvärdering av arbetsformer och lärande kan utformas

Sammanfattning I detta examensarbete undersöker jag ett sätt att bjuda in elever att medverka i skolans kvalitetsarbete. Avsikten är att konstruera en enkät för utvärdering av undervisning i år 9 och gymnasiet med det avseendet att mäta hur elever upplevt förutsättningar för lärande och förståelse av undervisningens innehåll. Detta sker genom att bjuda in elever från årskurs 9 att medverka till att påverka utformningen av enkäten. Syftet med enkäten är att undersöka hur elevers upplevda lärande och förståelse av ett visst innehåll kan stödjas genom val av arbets- och undervisningsform. Det är min önskan att finna en form för kvalitetsarbete i skolan där både elevsamverkan och lärande främjas. Den fråga jag ställer mig är: Hur kan elever i en arbetslagsgrupp i årskurs 9 medverka till att utvärdera och utforma en kursutvärderande enkät om upplevt lärande och förståelsen av innehåll i förhållande till arbetsform? För att besvara denna fråga har jag utformat en enkät i ämnet som i sin tur en elevgrupp har utvärderat i grupp. I anslutning till utvärderingen har jag intervjuat dem i grupp inom ramen för syftet. Mätinstrumentet, enkäten, är tänkt att användas i fortsatta studier inom samma ämne. I teoridelen redogör jag för vad våra styrdokument anser i frågan och vad forskningen anser om elevmedverkan och om vad de anser främjar elevers lärande och förståelse. I min slutsats konstaterar jag att det är möjligt att låta elever i årskurs 9 medverka till att utvärdera och utforma en kursutvärderande enkät om upplevt lärande och förståelsen av innehåll i förhållande till arbetsform. Elever kan anses ha en vilja att påverka sin egen studiesituation och det kan de göra med det övergripande ansvaret lagt på vuxna såsom pedagoger när det gäller det slutgiltiga resultatet. Nyckelord: Elevmedverkan, tematiskt arbete, lärand

User comments: Availability and Utilization in Online News Affiliated with Local Daily Press

User comments: Availability and Utilization in Online News Affiliated with Local Daily Press Author: Susanne Almgren Supervisor: Mats Ekström Constituent: Dagspresskollegiet (Annika Bergström/Ingela Wadbring) Course: Term Paper in Media and Communication Studies Term: Spring Term 2012 Pages/word count: 91 pages / 38 334 words Objective: To examine the users availability to the user comment feature and how the users utilizes the user comment feature in the context of an online news site affiliated with local daily press. Method: Mixed methods approach, content analysis and discourse analysis Main result: In this context, three out of four news stories (76.5 percent) has been allocated with the user comments feature. The highest availability to the user comment feature was found in news themes covering sports and entertainment, followed by financial news. News stories lacking the user comment feature were mainly found in news themes concerning crimes and accidents. The user comment frequencies are not normally distributed along news stories. On the contrary, 62 percent of the news stories did not get any user comments at all. The other news stories received user comments varying between one and 135. The user comments were highly oriented towards news stories covering the close proximity physical space, both its ordinary changing processes and issues of insecurity. Another news theme that received a high degree of user comments was connected to news stories covering politics in general. After that, the most commented news themes covered issues of health care and education. The news stories selected for the discourse analysis were chosen out of the most commented news stories. They shared the following characteristics: the voices heard in the news stories represented organizational or institutional voices, for example politicians, national union representatives, regional sport association spokesmen and the police. The users added an array of new discourses not represented by the news, by expanding the meaning of the news events in several ways