| 1. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Hanzén, Sarah, et al.
(författare)
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Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151
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Tidskriftsartikel (refereegranskat)abstract
- Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
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| 3. |
- Josefson, Rebecca, et al.
(författare)
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How and why do toxic conformers of aberrant proteins accumulate during ageing?
- 2017
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Ingår i: Essays in Biochemistry. - 0071-1365. ; 61:3, s. 317-324
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Tidskriftsartikel (refereegranskat)abstract
- Ageing can be defined as a gradual decline in cellular and physical functions accompanied by an increased sensitivity to the environment and risk of death. The increased risk of mortality is causally connected to a gradual, intracellular accumulation of so-called ageing factors, of which damaged and aggregated proteins are believed to be one. Such aggregated proteins also contribute to several age-related neurodegenerative disorders e.g. Alzheimer's, Parkinson's, and Huntington's diseases, highlighting the importance of protein quality control (PQC) in ageing and its associated diseases. PQC consists of two interrelated systems: the temporal control system aimed at refolding, repairing, and/or removing aberrant proteins and their aggregates and the spatial control system aimed at harnessing the potential toxicity of aberrant proteins by sequestering them at specific cellular locations. The accumulation of toxic conformers of aberrant proteins during ageing is often declared to be a consequence of an incapacitated temporal PQC system-i.e. a gradual decline in the activity of chaperones and proteases. Here, we review the current knowledge on PQC in relation to ageing and highlight that the breakdown of both temporal and spatial PQC may contribute to ageing and thus comprise potential targets for therapeutic interventions of the ageing process. © 2017 The Author(s).
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| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 5. |
- Andersson, Felicia, et al.
(författare)
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Resedagbok England/Wales - Arkitektur & teknik 2018
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Denna resedagbok är en del av Arkitektur och teknik- studenternas förberedelse för årskurs 3 och särskilt en träning i att söka, upptäcka och iakkta arkitekturens komplexa sammanhang och de värden som kan skapas genom arkitektur. Under studieresan byggs ett grundmaterial till dagboken upp genom förberedda presentationer, gemensamma analyser, undersökande skisser och konstnärliga övningar. Studieresan följs upp och bearbetas vid seminarier och genom korsläsning av texter där studenterna uppmanas till ett personligt reflekterande hållningssätt. På så sätt blir dagboken ett levande dokument som visar vår glädje och nyfikenhet över de många broar och byggnader vi upplevt tillsammans, och ett dokument som vill locka oss och alla läsare till vidare upptäcktsfärder.
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| 6. |
- Andersson, Rebecca, et al.
(författare)
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Career paths of Swedish top-level women soccer players
- 2019
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Ingår i: Soccer & Society. - : Informa UK Limited. - 1466-0970 .- 1743-9590. ; 20:6, s. 857-871
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Tidskriftsartikel (refereegranskat)abstract
- This study explores seven Swedish top-level women’s soccer players’ career development experiences. Data were produced through semi-structured interviews and a biographical mapping grid. The theoretical framework of ‘careership’ was employed to understand the data. The results showed homogenous career paths. Moreover, the data show that the players decided at a young age to pursue a career in soccer; experienced the transition from junior to senior level soccer as difficult because of a lack of physical preparedness; soccer over school commitments. We recommend that soccer stakeholders (e.g. federations, clubs, coaches) give the transition from junior to senior level soccer special attention to prevent intense demands that may cause dropout. We further propose that if athletes should give sport and education equal priority, the Swedish dual career concept of high school education and sport needs further reflection and adjustment.
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| 7. |
- Andersson, Rebecca, 1987-, et al.
(författare)
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The International Science Programme in Sri Lanka and Thailand : Three decades of research cooperation
- 2017. - 1
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Bok (populärvet., debatt m.m.)abstract
- Developing capacity for research and higher education takes time, especially in resource scarce environments. Equipping laboratories, building human capacity, and establishing research cultures at teaching oriented universities are complex and slow processes. This book focuses on the long-term cooperation with chemistry and physics research groups at universities in Sri Lanka and Thailand, provided by the International Science Programme (ISP) at Uppsala University, Sweden. It traces and gathers experiences from graduated students and other collaborating partners from supported groups. It addresses questions of if, and how, capacity for research and higher education has developed over the decades of ISP support, and the possible effects, efficiency, sustainability and improvements of it.
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| 8. |
- Andersson, Rebecca, 1987-
(författare)
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The Sandwich Model : A Successful Case of Capacity Building
- 2017
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Ingår i: Internationalisation of Higher Education - A Handbook. - Berlin, Germany. ; 1, s. 54-64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Based on the experiences of the International Science Programme (ISP) at Uppsala University, Sweden, this article describes and analyses the sandwich (PhD) model, where students from lower income countries spend part of their training at their home university and part at a better resourced university abroad. The model does more than provide scholarships; it includes long-term collaboration and commitment between partners, and improvement of research environments at students’ home institutions. By maintaining the connections to the home institutions throughout their training, conducting research of local relevance, and benefiting from enhanced research opportunities, graduates are facilitated to return home and continue their research after graduation.
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| 9. |
- Andersson, Rebecca, 1987-, et al.
(författare)
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Tracing ISP Graduates 2008-2013
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- The International Science Programme (ISP) at Uppsala University, Sweden, aims to contribute to the growth of scientific knowledge in Africa, Asia and Latin America. The ISP model is designed to prevent brain drain by improving local facilities and conditions for research and by promoting local postgraduate training. When local training is not possible, sandwich postgraduate training is employed, where students spend part of their training at their home university and part at a more resourceful scientific host institution abroad, in the North or in the region.The focus of this report is PhD graduates from ISP supported research groups and networks during the granting period 2008-2013, to trace where they are today and what they are doing.Most of the 154 traced PhD graduates (92%) are currently working in their home countries (126) or regions (16), most as Lecturers or Senior Lecturers at universities or research institutes. Twelve graduates are currently living in OECD countries, all but two of them employed in academia. A slightly higher share of students trained locally have stayed in their home countries or relocated within the regions, compared to sandwich students.
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| 10. |
- Andersson, Rebecca, 1987-
(författare)
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Tracing ISP Graduates 2014-2017
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The International Science Programme (ISP) at Uppsala University provides long-term financial and collegial support to institutionally based research groups and scientific networks in chemistry, mathematics and physics in Africa, Asia and Latin America.During 2014-2017, 259 PhD students have graduated from 43 ISP supported research groups and networks. This report aims to find out where these graduates go after graduation and if they are contributing to increased competence at their academic institutions or making use of their skills in other sectors or other countries.In all, 250 out of the 259 PhD graduates where traced with their present whereabouts. In line with previous ISP tracer studies, this study shows that 95% of the PhD graduates are employed in their home countries (89%) and regions (6%). A large majority (94%) is working at universities or research institutes, many holding positions as lecturers or assistant professors. Twelve graduates (5%) are currently working outside their home country and regions, most (83%) at academic institutions in these countries.
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