| 1. |
- Marriott, R. J., et al.
(author)
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Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study
- 2022
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1907-18
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Journal article (peer-reviewed)abstract
- Introduction: The association of testosterone concentrations with dementia risk remains uncertain. We examined associations of serum testosterone and sex hormone–binding globulin (SHBG) with incidence of dementia and Alzheimer's disease. Methods: Serum total testosterone and SHBG were measured by immunoassay. The incidence of dementia and Alzheimer's disease (AD) was recorded. Cox proportional hazards regression was adjusted for age and other variables. Results: In 159,411 community-dwelling men (median age 61, followed for 7 years), 826 developed dementia, including 288 from AD. Lower total testosterone was associated with a higher incidence of dementia (overall trend: P=.001, lowest vs highest quintile: hazard ratio [HR]=1.43, 95% confidence interval [CI]=1.13-1.81), and AD (P=.017, HR=1.80, CI=1.21-2.66). Lower SHBG was associated with a lower incidence of dementia (P<.001, HR=0.66, CI=0.51-0.85) and AD (P=.012, HR=0.53, CI=0.34-0.84). Discussion: Lower total testosterone and higher SHBG are independently associated with incident dementia and AD in older men. Additional research is needed to determine causality. © 2021 the Alzheimer's Association
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| 2. |
- Broadaway, K Alaine, et al.
(author)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Journal article (peer-reviewed)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 3. |
- Castin, N., et al.
(author)
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The effect of rhenium on the diffusion of small interstitial clusters in tungsten
- 2020
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In: Computational materials science. - : ELSEVIER. - 0927-0256 .- 1879-0801. ; 177
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Journal article (peer-reviewed)abstract
- In this work, we use atomistic simulations to investigate the mobility and stability of self-interstitial atom (SIA) clusters of size 1-5 in W-Re alloys. We apply molecular statics and molecular dynamics (MD) simulations to determine the dimensionality of diffusion of the clusters, the activation energy of translation and rotation, and the energy of dissociation. The results show a strong effect of Re on the diffusion properties of SIA clusters, but not on its stability. The diffusion mechanism of the single SIA changes from 1-D migration with on-site rotations to full 3-D diffusion on the MD time and length scale due to the addition of Re. Further, the mobility of the SIA clusters is greatly reduced by the addition of Re. The obtained results can be readily used to parameterize coarse grain models such as object kinetic Monte Carlo and rate theory models.
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| 4. |
- Keykhosravi, Kamran, 1990, et al.
(author)
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Semi-Passive 3D Positioning of Multiple RIS-Enabled Users
- 2021
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In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 70:10, s. 11073-11077
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Journal article (peer-reviewed)abstract
- Reconfigurable intelligent surfaces (RISs) are set to be a revolutionary technology in the 6th generation of wireless systems. In this work, we study the application of RIS in a multi-user passive localization scenario, where we have one transmitter (TX) and multiple asynchronous receivers (RXs) with known locations. Classical approaches fail in this scenario due to lack of synchronization and lack of data association between multi-static measurements and users. To resolve this, we consider each user to be equipped with an RIS, and show that we can avoid the data association problem and estimate users' 3D position with submeter accuracy in a large area around the transmitter, using time-of-arrival measurements at the RXs. We develop a low-complexity estimator that attains the corresponding Cram\'er-Rao bound as well as a novel RIS phase profile design to remove inter-path interference.
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| 6. |
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| 7. |
- Toldo, M, et al.
(author)
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Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme
- 2020
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In: BMJ open. - : BMJ. - 2044-6055. ; 10:11, s. e037335-
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Journal article (peer-reviewed)abstract
- Around 9% of India’s children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures.MethodsThis 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants’ GMs twice, that is, within 2 months after birth and at 3–5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12–24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12–24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA.Ethics and disseminationG.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.
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| 8. |
- Williamson, Alice, et al.
(author)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Journal article (peer-reviewed)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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