| 1. |
- Bergman, Lars R., et al.
(författare)
-
Individual development and adaptation (IDA) : A life-span longitudinal program suited for person-oriented research
- 2018
-
Ingår i: Journal for Person-Oriented Research. - : The Scandinavian Society for Person-Oriented Research (SPOR). - 2002-0244 .- 2003-0177. ; 4:2, s. 63-77
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, we give a presentation of the longitudinal research program Individual Development and Adaptation (IDA) that can be helpful as a template for researchers considering to launch their own longitudinal studies, and that opens the door to IDA for researchers looking for suitable data to be analyzed within their own project or in collaboration with IDA. We also introduce the holistic-interactionistic theoretical framework of IDA and the associated person-oriented approach – an approach that is especially suited for analyzing the rich IDA data set with its broad coverage of different areas of adjustment and related factors. The paper provides an overview of the essential features of the IDA database, as well as of ongoing and planned IDA research
|
|
| 2. |
- Gaulton, Kyle J, et al.
(författare)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Hastie, Roxanne, et al.
(författare)
-
Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women : A Swedish Population Register-Based Cohort Study
- 2019
-
Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 73:5, s. 1097-1103
-
Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia. The aim of this study was to determine the association between PPI use during pregnancy and preeclampsia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preeclampsia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preeclampsia (aOR of 1.17; 95% CI, 1.04-1.32) and preeclampsia at term (aOR of 1.20; 95% CI, 1.04-1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery <37 weeks) preeclampsia (aOR of 0.63; 95% CI, 0.41-0.96) and early (delivery <34 weeks) preeclampsia (aOR of 0.41; 95% CI, 0.20-0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preeclampsia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preeclampsia may help prevent this severe form of disease.
|
|
| 4. |
- Högfeldt, Anna-Karin, et al.
(författare)
-
Pedagogisk meritering på KTH - Samarbete, excellens och utbildningsinnovation
- 2019
-
Ingår i: Bidrag från 7:e Utvecklingskonferensen för Sveriges ingenjörsutbildningar. - Luleå : Luleå University of Technology. ; , s. 76-81
-
Konferensbidrag (refereegranskat)abstract
- Detta bidrag beskriver och analyserar förberedelsefasen inför implementeringen av ett högskolepedagogiskt excellensprogram vid Kungliga Tekniska Högskolan, KTH. Programmet syftar till att ytterligare stärka värdet av pedagogiska meriter och samtidigt bidra till lärosätets fortsatta och fördjupade utveckling av utbildningarna och organisationen. De tydligaste riskerna som har identifierats med befintliga pedagogiska meriteringsmodeller är att de kan skapa ett A- och B-lag (mellan en karriär som forskare och en karriär som lärare). Dessutom är det ofta oklart hur personer som har utnämnts till excellenta lärare ska kunna bidra till organisationens och utbildningens utveckling ur ett kortsiktigt såväl som ett långsiktigt perspektiv. En tydlig svaghet med befintliga pedagogiska meriteringsmodeller är att de inte explicit nog ger emfas till aktivt och relevant utvecklingsarbete, utan fokuserar på egenhändigt skrivna pedagogiska portföljer som sällan är framtidsinriktade. KTH:s högskolepedagogiska excellensprogram siktar på att försöka möta dessa risker och svagheter. KTH har, alltjämt sedan det nationella obligatoriet om 15 hp Högskolepedagogik infördes, kvarhållit detta obligatorium. Stora satsningar har gjorts på den högskolepedagogiska verksamheten. Ett gediget utbud av fortbildningsmöjligheter samt arenor för nätverkande har utvecklats. Samtidigt råder svagheter i systemet gällande prövande och tillvaratagande av pedagogisk skicklighet, och det är tydligt att KTH behöver ytterligare utveckling i området. Författarna menar också att i och med att de utmaningar vi står inför gällande pedagogisk meritering ser relativt lika ut vid landets lärosäten, bör ett stärkt nationellt samarbete och nätverkande inom landets ingenjörsutbildningar främjas inom området. Artikelförfattarna representerar KTH:s övergripande ledning, utbildningsledning samt ledningen för den högskolepedagogiska verksamheten.
|
|
| 5. |
- Kaufmann, Tobias, et al.
(författare)
-
Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
-
Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
-
Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
|
|
| 6. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 7. |
- Alnaes, Dag, et al.
(författare)
-
Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
-
Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
-
Tidskriftsartikel (refereegranskat)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
|
|
| 8. |
|
|
| 9. |
- Azasu, S, et al.
(författare)
-
CDIO in Africa
- 2019
-
Ingår i: <em>Proceedings of the 15th International CDIO Conference</em>.
-
Konferensbidrag (refereegranskat)
|
|
| 10. |
- Bergman, Lina, 1982-
(författare)
-
Cerebral biomarkers in women with preeclampsia
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
|
|
