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- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 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
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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- Petersson, E-L, et al.
(författare)
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Examining the description of the concept "treatment as usual" for patients with depression, anxiety and stress-related mental disorders in primary health care research - A systematic review.
- 2023
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Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 326, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- In randomized controlled trials (RCTs) within medical research, applied interventions are compared to treatment-as-usual (TAU) as the control condition. The aim of the current study was to examine how the concept of TAU is described when used as control condition in RCTs evaluating treatments for depression, anxiety syndromes, and stress-related mental disorders in primary care.A systematic review of RCTs utilizing TAU as control group in the RCT in accordance with PRISMA standards was conducted. We used one multidisciplinary database (Scopus), one database focused on nursing (Cinahl), and one medical database (PubMed). The searches were conducted in November 2021 and May 2022.The included 32 studies comprised of 7803 participants. The content of TAU was classified as follows: 1) Basic descriptions of TAU lacking a detailed account as well as reference to local or national guidelines, 2) Moderate description of TAU including reference to national or local guidelines or a detailed description 3) Advanced description of TAU including references to national guidelines and a detailed description containing five key concepts: early assessment, accessibility, psychological treatment, medication, somatic examination. 18 studies had basic, 11 moderate, and 3 advanced descriptions of TAU.The limitations were that only studies published in English were included.The current study provides an assessment tool with three classification levels for TAU. The description of TAU is still insufficient in RCT studies conducted in primary care, which may affect the interpretation of results. In future research a detailed description of TAU is recommended.
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- Ahlqvist, E., et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
- 2018
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis. Methods We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA(1c), and homoeostatic model assessment 2 estimates of beta-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations. Findings We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. Interpretation We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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- Forsen, E, et al.
(författare)
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Fabrication of cantilever based mass sensors integrated with CMOS using direct write laser lithography on resist
- 2004
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Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 15:10, s. 628-633
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Tidskriftsartikel (refereegranskat)abstract
- A CMOS compatible direct write laser lithography technique has been developed for cantilever fabrication on pre-fabricated standard CMOS. We have developed cantilever based sensors for mass measurements in vacuum and air. The cantilever is actuated into lateral vibration by electrostatic excitation and the resonant frequency is detected by capacitive readout. The device is integrated on standard CMOS circuitry. In the work a new direct write laser lithography (DWL) technique is introduced. This laser lithography technique is based on direct laser writing on substrates coated with a resist bi-layer consisting of poly(methyl methacrylate) (PMMA) on lift-off resist (LOR). Laser writing evaporates the PMMA, exposing the LOR. A resist solvent is used to transfer the pattern down to the substrate. Metal lift-off followed by reactive ion etching is used for patterning the structural poly-Si layer in the CMOS. The developed laser lithography technique is compatible with resist exposure techniques such as electron beam lithography. We demonstrate the fabrication of sub-micrometre wide suspended cantilevers as well as metal lift-off with feature line widths down to approximately 500 nm.
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- Forsen, E, et al.
(författare)
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Ultrasensitive mass sensor fully integrated with complementary metal-oxide-semiconductor circuitry
- 2005
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:4
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Tidskriftsartikel (refereegranskat)abstract
- Nanomechanical resonators have been monolithically integrated on preprocessed complementary metal-oxide-semiconductor (CMOS) chips. Fabricated resonator systems have been designed to have resonance frequencies up to 1.5 MHz. The systems have been characterized in ambient air and vacuum conditions and display ultrasensitive mass detection in air. A mass sensitivity of 4 ag/Hz has been determined in air by placing a single glycerine drop, having a measured weight of 57 fg, at the apex of a cantilever and subsequently measuring a frequency shift of 14.8 kHz. CMOS integration enables electrostatic excitation, capacitive detection, and amplification of the resonance signal directly on the chip.
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