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- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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- Sisask, M, et al.
(författare)
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Teacher satisfaction with school and psychological well-being affects their readiness to help children with mental health problems
- 2014
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Ingår i: HEALTH EDUCATION JOURNAL. - : SAGE Publications. - 0017-8969 .- 1748-8176. ; 73:4, s. 382-393
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In support of a whole-school approach to mental health promotion, this study was conducted to find out whether and how significantly teachers’ satisfaction with school and their subjective psychological well-being are related to the belief that they can help pupils with mental health problems. Design: Cross-sectional data were collected as a part of the European Union’s, Seventh Framework Programme for Research (FP7) Saving and Empowering Young Lives in Europe (SEYLE) study. One of the elements of the SEYLE study was to evaluate teachers’ attitudes and knowledge related to pupils’ mental health issues and their own psychological well-being, as well as their satisfaction with the school environment. Setting: The sample of schools from the SEYLE study sites representing 11 European countries was randomly chosen according to prior defined inclusion and exclusion criteria. The final cross-sectional database used for analysis in the current study comprised 2485 teachers from 158 randomly selected schools. Method: Respondents’ belief that teachers can help pupils with mental health problems served as the outcome variable in our predictions with probability of the positive answer being modelled in the logistic regression analysis. Teachers’ subjective psychological well-being and school satisfaction were included as independent variables in the logistic regression model and several other relevant variables were added to statistically control for them. Multiple models were tested in order to obtain the final model. Results: Logistic regression models showed that better satisfaction with general school climate, higher psychological well-being, and the ability to understand pupils’ mental health problems increased the odds of teachers’ readiness to help pupils with mental health problems. Conclusion: By providing a good school environment, by valuing the subjective psychological well-being of the teachers, and by providing adequate training to fulfil their ‘gatekeeper’ role, the preconditions to improve the mental health of the pupils they teach will be achieved. These suggestions are in line with a whole-school approach to mental health promotion.
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- Kabudula, Chodziwadziwa W., et al.
(författare)
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Evaluation of record linkage of mortality data between a health and demographic surveillance system and national civil registration system in South Africa
- 2014
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Ingår i: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health and Demographic Surveillance Systems (HDSS) collect independent mortality data that could be used for assessing the quality of mortality data in national civil registration (CR) systems in low- and middle-income countries. However, the use of HDSS data for such purposes depends on the quality of record linkage between the two data sources. We describe and evaluate the quality of record linkage between HDSS and CR mortality data in South Africa with HDSS data from Agincourt HDSS. Methods: We applied deterministic and probabilistic record linkage approaches to mortality records from 2006 to 2009 from the Agincourt HDSS and those in the CR system. Quality of the matches generated by the probabilistic approach was evaluated using sensitivity and positive predictive value (PPV) calculated from a subset of records that were linked using national identity number. Matched and unmatched records from the Agincourt HDSS were compared to identify characteristics associated with successful matching. In addition, the distribution of background characteristics in all deaths that occurred in 2009 and those linked to CR records was compared to assess systematic bias in the resulting record-linked dataset in the latest time period. Results: Deterministic and probabilistic record linkage approaches combined linked a total of 2264 out of 3726 (60.8%) mortality records from the Agincourt HDSS to those in the CR system. Probabilistic approaches independently linked 1969 (87.0%) of the linked records. In a subset of 708 records that were linked using national identity number, the probabilistic approaches yielded sensitivity of 90.0% and PPV of 98.5%. Records belonging to more vulnerable people, including poorer persons, young children, and non-South Africans were less likely to be matched. Nevertheless, distribution of most background characteristics was similar between all Agincourt HDSS deaths and those matched to CR records in the latest time period. Conclusion: This study shows that record linkage of mortality data from HDSS and CR systems is possible and can be useful in South Africa. The study identifies predictors for death registration and data items and registration system characteristics that could be improved to achieve more optimal future matching possibilities.
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- Gómez-Olivé, F Xavier, et al.
(författare)
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Assessing health and well-being among older people in rural South Africa
- 2010
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Ingår i: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9716. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- This study presents the first population-based data from South Africa on health status, functional ability and quality of life among older people. Health and social services will need to be restructured to provide effective care for older people living in rural South Africa with impaired functionality and other health problems.
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| 29. |
- Groome, Michelle J., et al.
(författare)
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Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children : a case-control study
- 2014
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Ingår i: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 14:11, s. 1096-1104
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Tidskriftsartikel (refereegranskat)abstract
- Background The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. Methods This case-control study was done at seven hospitals in South Africa between April 19,2010, and Oct 31,2012. The hospitals were located in a range of urban, pen-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14,2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 adjusted odds ratio x100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Findings Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Interpretation Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries.
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| 30. |
- Hawkesworth, Sophie, et al.
(författare)
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Combined Food and Micronutrient Supplements during Pregnancy Have Limited Impact on Child Blood Pressure and Kidney Function in Rural Bangladesh
- 2013
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 143:5, s. 728-734
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Tidskriftsartikel (refereegranskat)abstract
- Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health; data from interventions are scarce. Here, we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and childhood blood pressure and kidney function. During the MINIMat Trial in rural Bangladesh, women were randomly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily. The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old. A total of 77% of eligible individuals were recruited and blood pressure, kidney size by ultrasound, and glomerular filtration rate (GFR; calculated from plasma cystatin c) were assessed. In adjusted analysis, early invitation to food supplementation was associated with a 0.72-mm Hg [(95% CI: 0.16, 1.28); P = 0.01] lower childhood diastolic blood pressure and maternal MMS supplementation was associated with a marginally higher [0.87 mm Hg (95% CI: 0.18, 1.56); P = 0.01] childhood diastolic blood pressure. There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR. No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied. These marginal associations and small effect sizes suggest limited public health importance in early childhood.
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| 31. |
- Joubert, Jané, et al.
(författare)
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Record-linkage comparison of verbal autopsy and routine civil registration death certification in rural north-east South Africa : 2006-09
- 2014
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:6, s. 1945-1958
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Tidskriftsartikel (refereegranskat)abstract
- Background: South African civil registration (CR) provides a key data source for local health decision making, and informs the levels and causes of mortality in data-lacking sub-Saharan African countries. We linked mortality data from CR and the Agincourt Health and Socio-demographic Surveillance System (Agincourt HDSS) to examine the quality of rural CR data. Methods: Deterministic and probabilistic techniques were used to link death data from 2006 to 2009. Causes of death were aggregated into the WHO Mortality Tabulation List 1 and a locally relevant short list of 15 causes. The matching rate was compared with informant-reported death registration. Using the VA diagnoses as reference, misclassification patterns, sensitivity, positive predictive values and cause-specific mortality fractions (CSMFs) were calculated for the short list. Results: A matching rate of 61% [95% confidence interval (CI): 59.2 to 62.3] was attained, lower than the informant-reported registration rate of 85% (CI: 83.4 to 85.8). For the 2264 matched cases, cause agreement was 15% (kappa 0.1083, CI: 0.0995 to 0.1171) for the WHO list, and 23% (kappa 0.1631, CI: 0.1511 to 0.1751) for the short list. CSMFs were significantly different for all but four (tuberculosis, cerebrovascular disease, other heart disease, and ill-defined natural) of the 15 causes evaluated. Conclusion: Despite data limitations, it is feasible to link official CR and HDSS verbal autopsy data. Data linkage proved a promising method to provide empirical evidence about the quality and utility of rural CR mortality data. Agreement of individual causes of death was low but, at the population level, careful interpretation of the CR data can assist health prioritization and planning.
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| 32. |
- Kahn, Kathleen, et al.
(författare)
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Profile : Agincourt Health and Socio-demographic Surveillance System
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:4, s. 988-1001
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Tidskriftsartikel (refereegranskat)abstract
- The Agincourt health and socio-demographic surveillance system (HDSS), located in rural northeast South Africa close to the Mozambique border, was established in 1992 to support district health systems development led by the post-apartheid ministry of health. The HDSS (90 000 people), based on an annual update of resident status and vital events, now supports multiple investigations into the causes and consequences of complex health, population and social transitions. Observational work includes cohorts focusing on different stages along the life course, evaluation of national policy at population, household and individual levels and examination of household responses to shocks and stresses and the resulting pathways influencing health and well-being. Trials target children and adolescents, including promoting psycho-social well-being, preventing HIV transmission and reducing metabolic disease risk. Efforts to enhance the research platform include using automated measurement techniques to estimate cause of death by verbal autopsy, full 'reconciliation' of in- and out-migrations, follow-up of migrants departing the study area, recording of extra-household social connections and linkage of individual HDSS records with those from sub-district clinics. Fostering effective collaborations (including INDEPTH multi-centre work in adult health and ageing and migration and urbanization), ensuring cross-site compatibility of common variables and optimizing public access to HDSS data are priorities.
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| 34. |
- Mather, K J, et al.
(författare)
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Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.
- 2012
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491.
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Tidskriftsartikel (refereegranskat)abstract
- Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions from rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
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| 35. |
- Mello, D. A. A., et al.
(författare)
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Optical Networking With Variable-Code-Rate Transceivers
- 2014
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Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 32:2, s. 257-266
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate the impact of variable-code-rate transceivers on cost, capacity and survivability of wavelength-routed optical networks. The transmission rate and reach trade-off is quantified for two hypothetical coded modulation schemes (aggressive and conservative) in a wavelength routing network with 50-GHz-spaced channels. The aggressive scenario assumes the 64-QAM modulation format, a small gap to capacity, and a small excess bandwidth. The conservative scenario considers the 16-QAM modulation format, and a larger capacity gap and excess bandwidth. The performance of the conservative and aggressive technologies is evaluated in three representative networks. Transparent reaches are calculated by means of an existing analytical method which assumes the AWGN hypothesis for the nonlinear noise. It is shown that variable-code-rate transceivers enable the concept of soft protection, in which the protection lightpath operates at a data rate which is lower than the corresponding working lightpath, in a way to avoid regeneration. This is specially attractive in the transport of IP traffic, where capacity reduction (in average up to 25%) may be tolerable during a repair time. It is also shown that variable-code-rate transceivers have the potential to offer significant savings in terms of transceiver usage and wavelength occupation, when compared to current fixed-rate transceivers operating at 100, 200 or 400 Gb/s. Finally, practical variable-code-rate transceivers may achieve a discrete set of N code rates, yielding a quantized capacity-versus-reach curve. The system impact of N is evaluated for several network scenarios.
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| 36. |
- Norseen, J., et al.
(författare)
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Retinol-Binding Protein 4 Inhibits Insulin Signaling in Adipocytes by Inducing Proinflammatory Cytokines in Macrophages through a c-Jun N-Terminal Kinase- and Toll-Like Receptor 4-Dependent and Retinol-Independent Mechanism
- 2012
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Ingår i: Molecular and Cellular Biology. - : Informa UK Limited. - 0270-7306 .- 1098-5549. ; 32:10, s. 2010-2019
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Tidskriftsartikel (refereegranskat)abstract
- Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. RBP4 effects are markedly attenuated in JNK1(-/-) JNK2(-/-) macrophages and TLR4(-/-) macrophages. Because RBP4 is a retinol-binding protein, we investigated whether these effects are retinol dependent. Unexpectedly, retinol-free RBP4 (apo-RBP4) is as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory cytokines in macrophages. Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4.
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| 37. |
- Owen, Carl, et al.
(författare)
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Adipocyte-Specific Protein Tyrosine Phosphatase 1B Deletion Increases Lipogenesis, Adipocyte Cell Size and Is a Minor Regulator of Glucose Homeostasis
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively establish the role of adipocyte-PTP1B in body mass regulation and glucose homeostasis, adipocyte-specific-PTP1B knockout mice (adip-crePTP1B(-/-)) were generated using the adiponectin-promoter to drive Cre-recombinase expression. Chow-fed adip-crePTP1B(-/-) mice display enlarged adipocytes, despite having similar body weight/adiposity and glucose homeostasis compared to controls. High-fat diet (HFD)-fed adip-crePTP1B(-/-) mice display no differences in body weight/adiposity but exhibit larger adipocytes, increased circulating glucose and leptin levels, reduced leptin sensitivity and increased basal lipogenesis compared to controls. This is associated with decreased insulin receptor (IR) and Akt/PKB phosphorylation, increased lipogenic gene expression and increased hypoxia-induced factor-1-alpha (Hif-1 alpha) expression. Adipocyte-specific PTP1B deletion does not beneficially manipulate signaling pathways regulating glucose homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes.
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| 38. |
- Sartorius, Benn K D, et al.
(författare)
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Young and vulnerable : spatial-temporal trends and risk factors for infant mortality in rural South Africa (Agincourt), 1992-2007
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10, s. 645-
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Tidskriftsartikel (refereegranskat)abstract
- This study demonstrates the use of Bayesian geostatistical models in assessing risk factors and producing smooth maps of infant mortality risk in a health and socio-demographic surveillance system. Results showed marked geographical differences in mortality risk across a relatively small area. Prevention of vertical transmission of HIV and survival of mothers during the infants' first year in high prevalence villages needs to be urgently addressed, including expanded antenatal testing, prevention of mother-to-child transmission, and improved access to antiretroviral therapy. There is also need to assess and improve the capacity of district hospitals for emergency obstetric and newborn care. Persisting risk factors, including inadequate provision of clean water and sanitation, are yet to be fully addressed.
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| 39. |
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| 40. |
- Wagner, Ryan G., et al.
(författare)
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Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa
- 2014
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 108:4, s. 782-791
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Epilepsy is among the most common neurological disorders there are few large, population-based studies of the prevalence and risk southern Africa. Methods: From August 2008 to February 2009, as part of a multi-site study, we undertook a three-stage, population-based study, embedded within the Agincourt health and socio-demographic surveillance system, to estimate the prevalence and identify risk factors of active convulsive epilepsy (ACE) in a rural South African population. Results: The crude prevalence of ACE, after adjusting for non-response and the sensitivity of the screening method, was 7.0/1,000 individuals (95%CI 6.4-7.6) with significant geographic heterogeneity across the study area. Being male (OR= 2.3; 95%CI 1.6-3.2), family history of seizures (OR =4.0; 95%CI 2.0-8.1), a sibling with seizures (OR = 7.0; 95%CI 1.6-31.7), problems after delivery (OR= 5.9; 95%CI 1.2-24.6), and history of snoring (OR =6.5; 95%CI 4.5-9.5) were significantly associated with ACE. For children, their mother's exposure to some formal schooling was protective (OR = 0.30; 95%CI 0.11-0.84) after controlling for age and sex. Human immunodeficiency virus was not found to be associated with ACE. Conclusions: ACE is less frequent in this part of rural South Africa than other parts of sub-Saharan Africa. Improving obstetric services could prevent epilepsy. The relationship between snoring and ACE requires further investigation, as does the relative contribution of genetic and environmental factors to examine the increased risk in those with a family history of epilepsy. (C) 2014 Elsevier B.V. All rights reserved.
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| 41. |
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| 42. |
- Yore, M. M., et al.
(författare)
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Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects
- 2014
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 159:2, s. 318-332
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Tidskriftsartikel (refereegranskat)abstract
- Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
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