| 1. |
- Wang, Li-San, et al.
(författare)
-
Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
|
|
| 2. |
- Roselli, Carolina, et al.
(författare)
-
Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
-
Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
|
|
| 3. |
- Willeit, Peter, et al.
(författare)
-
Natriuretic peptides and integrated risk assessment for cardiovascular disease : an individual-participant-data meta-analysis
- 2016
-
Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 4:10, s. 840-849
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7.5%, and >= 7.5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. Findings: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1.76 (95% CI 1.56-1.98) for the combination of coronary heart disease and stroke and 2.00 (1.77-2.26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0.012 (0.010-0.014) and a net reclassification improvement of 0.027 (0.019-0.036) for the combination of coronary heart disease and stroke and a C-index increase of 0.019 (0.016-0.022) and a net reclassification improvement of 0.028 (0.019-0.038) for the combination of coronary heart disease, stroke, and heart failure. Interpretation: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.
|
|
| 4. |
- Wallin, Anders, 1950, et al.
(författare)
-
Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.
- 2017
-
Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 17:1
-
Forskningsöversikt (refereegranskat)abstract
- Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption;altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
|
|
| 5. |
- Hjelm-Wallén, Lena, et al.
(författare)
-
Det behövs mer än värnplikt
- 2016
-
Ingår i: Svenska dagbladet. - 1101-2412. ; :2016-10-07, s. 6-6
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Människors säkerhet handlar om mycket mer än det rent militära. Därför är det är dags att överväga att införa allmän medborgartjänst för alla medborgare kring tjugoårsåldern.
|
|
| 6. |
- Rosenberg, Molly, et al.
(författare)
-
Relationship Between Community-Level Alcohol Outlet Accessibility and Individual-Level Herpes Simplex Virus Type 2 Infection Among Young Women in South Africa
- 2015
-
Ingår i: Sexually Transmitted Diseases. - 0148-5717 .- 1537-4521. ; 42:5, s. 259-265
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to alcohol outlets may influence sexual health outcomes at the individual and community levels. Visiting alcohol outlets facilitates alcohol consumption and exposes patrons to a risky environment and network of potential partners, whereas the presence of alcohol outlets in the community may shift social acceptance of riskier behavior. We hypothesize that living in communities with more alcohol outlets is associated with increased sexual risk. Methods: We performed a cross-sectional analysis in a sample of 2174 South African schoolgirls (ages 13-21 years) living across 24 villages in the rural Agincourt subdistrict, underpinned by long-term health and sociodemographic surveillance. To examine the association between number of alcohol outlets in village of residence and individual-level prevalent herpes simplex virus type 2 (HSV-2) infection, we used generalized estimating equations with logit links, adjusting for individual-and villagelevel covariates. Results: The median number of alcohol outlets per village was 3 (range, 0-7). Herpes simplex virus type 2 prevalence increased from villages with no outlets (1.4%[95% confidence interval, 0.2-12.1]), to villages with 1 to 4 outlets (4.5% [3.7-5.5]), and to villages with more than 4 outlets (6.3% [5.6, 7.1]). An increase of 1 alcohol outlet per village was associated with an 11% increase in the odds of HSV-2 infection (adjusted odds ratio [95% confidence interval], 1.11 [0.98-1.25]). Conclusions: Living in villages with more alcohol outlets was associated with increased prevalence of HSV-2 infection in young women. Structural interventions and sexual health screenings targeting villages with extensive alcohol outlet environments could help prevent the spread of sexually transmitted infections.
|
|
| 7. |
- Rosenberg, Molly, et al.
(författare)
-
Relationship between school dropout and teen pregnancy among rural South African young women
- 2015
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:3, s. 928-936
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sexual activity may be less likely to occur during periods of school enrolment because of the structured and supervised environment provided, the education obtained and the safer peer networks encountered while enrolled. We examined whether school enrolment was associated with teen pregnancy in South Africa. Methods: Using longitudinal demographic surveillance data from the rural Agincourt sub-district, we reconstructed the school enrolment status from 2000 through 2011 for 15 457 young women aged 12-18 years and linked them to the estimated conception date for each pregnancy during this time. We examined the effect of time-varying school enrolment on teen pregnancy using a Cox proportional hazard model, adjusting for: age; calendar year; household socioeconomic status; household size; and gender, educational attainment and employment of household head. A secondary analysis compared the incidence of pregnancy among school enrolees by calendar time: school term vs school holiday. Results: School enrolment was associated with lower teen pregnancy rates [adjusted hazard ratio (95% confidence interval): 0.57 (0.50, 0.65)]. This association was robust to potential misclassification of school enrolment. For those enrolled in school, pregnancy occurred less commonly during school term than during school holidays [incidence rate ratio (95% confidence interval): 0.90 (0.78, 1.04)]. Conclusions: Young women who drop out of school may be at higher risk for teen pregnancy and could likely benefit from receipt of accessible and high quality sexual health services. Preventive interventions designed to keep young women in school or addressing the underlying causes of dropout may also help reduce the incidence of teen pregnancy.
|
|
