| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Eriksson, Ann-Marie, 1964, et al.
(författare)
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Swedish language advisors’ textually mediated encounters with dilemmas in their writing centre consultations.
- 2023
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Ingår i: Paper presented at Writing Research Across Borders, WRAB2023. NTNU, Norway. 18-22 February 2023..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This presentation reports an ongoing research project investigating the development and professionalization of centralized support for academic language and writing in Swedish universities. While research on this kind of literacy support has a long tradition and has been carried out in many parts of the world (Essid & McTague, 2020), the Swedish context represents a case where centralization is recent and still unregulated (Lennartson-Hokkanen, 2016). Universities can therefore organise support for academic writing and language autonomously and according to their own specific needs and purposes. A strong growth in numbers of centralized support units has been noticed recently (Bjernhage & Grönvall Fransson, 2017). This growth comes in the wake of increased mobility, internationalisation, and broadening participation (Kaufhold & Yenken, 2021). What also makes the Swedish context important to study is that central units of this kind usually recruit teachers, academics and scholars as professional advisors, whereas peer tutoring is rare. Staff members come from a variety of educational backgrounds, but a strong grounding in the field of Linguistics or Languages is common. However, our material shows that the everyday work for language advisors implies pedagogically demanding situations where students’ expectations on immediate text improvement at the level of grammar and text structure collide with advisors’ ambitions to serve each individual in the best of ways and provide ‘strategies’ for writing that point beyond the immediate text. So, advising exemplifies a pedagogical academic literacy practice where an intricate mix of institutionally grounded tensions need to be handled by individual advisors in the role of literacy experts. The objective of the project to be reported is therefore to demonstrate how academic literacy expertise, specifically required for scaffolding students’ writing through advising sessions, is being developed through situations requiring expert judgment and actions. The primary empirical data consists of a collection of video-recordings from a series of professional competence development workshops that were carried out 2021-2022. In these workshops, staff members from centralized writing centres in four different Swedish universities met for the purpose of sharing their advising experiences and discussing specific challenges and dilemmas. Each participating university took responsibility for organizing one workshop and each workshop consisted of a mix of whole group activities and group-work. In the smaller groups, individual advisors were teamed up with colleagues from the other contributing universities and thus came to represent their own writing centre and institution. The video-material is complemented by a collection of texts participants produced and used as part of the workshops. The conversational nature of these workshops allows for a dialogical approach (Linell, 2021) to how relevant literacy expertise is mediated as individual professional advisors from different institutions work with sample dilemmas. Such a theoretical grounding implies analytical attention to how the participants interactively anticipate and coordinate with each other as they share and discuss their individual samples. A series of textually mediated activities have been selected and transcribed. The currently ongoing analytical work is guided by the following questions: - How is academic literacy expertise produced and moulded in the interaction around the participants’ sample dilemmas? - What means for solutions to problems are introduced and made relevant by the participants? The contributions of this research are partly empirical, partly methodological. While writing centres and writing centre practice have been extensively studied (e.g. Mackiewicz & Thompson, 2018), the underpinnings of the Swedish case are comparatively under-explored. This study adds to organisational and practice perspectives in the field of writing research as it attends to professional advising as a pedagogical and epistemologically grounded practice. Findings so far indicate a series of tensions that seem to characterise the Swedish context specifically, and significant professional development processes for individual writing centre staff members. For example, professional advisors’ literacy expertise involves balancing historically developed notions of ‘language’ vs. ‘writing’ and appropriating a developmental view of students’ needs.
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| 5. |
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| 6. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 7. |
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| 8. |
- Nord, Andreas, professor, 1976-, et al.
(författare)
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Språkhandledares gränsarbete : Dilemman i språkhandledning inom högre utbildning
- 2023
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Ingår i: Ämnesdidaktiska perspektiv på språk och litteratur. - Uppsala : Institutionen för nordiska språk, Uppsala universitet. - 1651-9132. - 9789198695045 - 9789198695052 ; , s. 159-182
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Konferensbidrag (refereegranskat)abstract
- De flesta svenska lärosäten har i dag språkverkstäder med uppdraget att stötta studenterna i utvecklingen av akademiska språkliga praktiker. Trots att uppdraget har en stark koppling till universitetens kärnverksamheter utbildning och forskning organiseras verksamheterna i allmänhet i marginalen, inom ramen för service- eller stödfunktioner. I denna studie utforskas hur verksamma språkhandledare från språkverkstäder vid fyra lärosäten i kollegiala gruppsamtal talar om egna exempel från verksamheten, särskilt sådana som innebär professionella dilemman. Syftet är att synliggöra det ”gränsarbete” på olika nivåer som behöver utföras för att hantera yrkesutövandet genom att förhålla sitt eget handlande till andra intressenters handlande och förväntningar och verksamhetens underliggande villkor.Analysen visar att gränsarbete är centralt för språkhandledarnas professionella praktik, genom att många av de dilemman som deltagarna redogör för berör ansvarsrelationer och frågor om vad språkhandledaren ska göra – och inte göra – i relation till studenter, universitetslärare och i viss mån även i relation till organisatoriska förutsättningar. En vanlig gränsproblematik är t.ex. att behöva hantera att studenter kan utgå från en avvikande uppfattning om var gränserna går för vad språkhandledarna kan och ska bidra med än den språkhandledarna har. Till problematiken hör att möta förväntningar om att, som det uttrycks i materialet, ”rätta” eller ”fixa” texter.Resultaten relateras till tidigare forskning som diskuterat hur en s.k. autonom syn på litteracitet genomsyrar akademin och skapar en förståelse av litteracitet som individuell färdighet och språk som något som enkelt kan ”fixas”. Utifrån detta diskuteras hur språkverkstädernas marginaliserade position riskerar att bidra till att reproducera en sådan syn.
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| 9. |
- Schriever, Valentin A., et al.
(författare)
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Development of an International Odor Identification Test for Children : The Universal Sniff Test
- 2018
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Ingår i: The Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 198, s. 265-272
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test.Study designThis is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). Results Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean +/- SD of 9.88 +/- 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r(27) = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%.ConclusionsThe U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.
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| 10. |
- Addo, Rebecka N., et al.
(författare)
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Olfactory Functions in Adults With Autism Spectrum Disorders
- 2017
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Ingår i: Perception. - : SAGE Publications. - 0301-0066 .- 1468-4233. ; 46:3-4, s. 530-537
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.
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