| 61. |
- Lind, Susanne, et al.
(författare)
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Implementation of national palliative care guidelines in Swedish acute care hospitals: A qualitative content analysis of stakeholders’ perceptions
- 2017
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Ingår i: Health Policy. - : Elsevier BV. - 0168-8510 .- 1872-6054. ; 121:11, s. 1194-1201
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Tidskriftsartikel (refereegranskat)abstract
- In high-income countries a large proportion of all deaths occur in hospitals. A common way to translate knowledge into clinical practice is developing guidelines for different levels of health care organisations. During 2012, national clinical guidelines for palliative care were published in Sweden. Later, guidance for palliative care was issued by the National Board of Health and Welfare. The aim of this study was two-fold: to investigate perceptions regarding these guidelines and identify obstacles and opportunities for implementation of them in acute care hospitals. Interviews were conducted with local politicians, chief medical officers and health professionals at acute care hospitals. The Consolidated Framework for Implementation Research was used in a directed content analysis approach. The results showed little knowledge of the two documents at all levels of the health care organisation. Palliative care was primarily described as end of life care and only few of the participants talked about the opportunity to integrate palliative care early in a disease trajectory. The environment and culture at hospitals, characterised by quick decisions and actions, were perceived as obstacles to implementation. Health professionals' expressed need for palliative care training is an opportunity for implementation of clinical guidelines. There is a need for further implementation of palliative care in hospitals. One option for further research is to evaluate implementation strategies tailored to acute care. © 2017 Elsevier B.V.
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| 62. |
- Maddock, Jane, et al.
(författare)
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Vitamin D and cognitive function : A Mendelian randomisation study.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.
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| 63. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 64. |
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| 65. |
- Marklund, Matti, et al.
(författare)
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Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations
- 2017
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 147:11, s. 2118-2125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acid (FA) proportions in cholesterol esters (CEs) and plasma phospholipids are widely used as dietary biomarkers. Information on how proportions in these fractions correlate could have implications for interpretation and use of FA biomarkers in observational and interventional studies. Objective: We investigated correlations between FA proportions in CEs and phospholipids in free-living individuals and assessed how diet-induced alterations of FA proportions correlate between fractions. Methods: Spearman's rank correlation coefficients (rs) between FA proportions (percentage of total FAs) in circulating CEs and phospholipids were calculated separately in 8 individual study populations including Swedish females and males (N = 2052; age range: 11-84 y), and pooled by inverse-variance weighted meta-analysis. In addition, study populations were stratified by age, sex, body mass index (BMI; in kg/m(2)), and diabetes status, and strata-specific rs were pooled by meta-analysis. In 2 randomized trials (N = 79) in which dietary saturated FAs were isocalorically replaced with unsaturated FAs, treatment-wise calculations of rs were conducted between FA changes in CEs and phospholipids. Results: Overall, FA proportions in CEs and phospholipids correlated well and especially strongly for polyunsaturated FAs (PUFAs), with pooled rs (95% CIs) ranging from 0.74 (0.72, 0.76) for a-linolenic acid to 0.92 (0.91, 0.93) for eicosapentaenoic acid. Weak correlations (pooled rs <0.4) were observed only for palmitic acid and stearic acid, with pooled rs (95% CIs): 0.29 (0.24, 0.33) and 0.30 (0.25, 0.34), respectively. Overall, correlations were not affected by age, sex, BMI, or diabetes status. Strong correlations (r(s) >= 0.6) between diet-induced FA changes in CEs and phospholipids were observed for most PUFAs. Conclusions: Proportions of most FAs in CEs and phospholipids ranked individuals similarly, suggesting that FA proportions in these fractions can be used interchangeably in populations of diverse age, sex, body composition, and diabetes status. Caution is advised, however, when comparing results from studies assessing palmitic acid or stearic acid in different lipid fractions.
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| 66. |
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| 67. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 68. |
- Memisevic, Elvedin, et al.
(författare)
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Impact of Band-Tails on the Subthreshold Swing of III-V Tunnel Field-Effect Transistor
- 2017
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Ingår i: IEEE Electron Device Letters. - 0741-3106. ; , s. 1661-1664
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Tidskriftsartikel (refereegranskat)abstract
- We present a simple model to evaluate the sharpness of the band edges for tunnel field-effect transistors by comparing the subthreshold swing and the conductance in the negative differential resistance region. This model is evaluated using experimental data from InAs/InGaAsSb/GaSb nanowire tunnel-field effect transistors with the ability to reach a subthreshold swing well below the thermal limit. A device with the lowest subthreshold swing, 43 mV/decade at 0.1 V, exhibits also the sharpest band-edge decay parameter E0 of 43.5 mV although in most cases the S<
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| 69. |
- Memisevic, Elvedin, et al.
(författare)
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InAs/InGaAsSb/GaSb Nanowire Tunnel Field-Effect Transistors
- 2017
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383. ; 64:11, s. 4746-4751
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Tidskriftsartikel (refereegranskat)abstract
- Tunnel field-effect transistors with ability to operate well below the thermal limit (with a demonstrated 43 mV/decade at VDS = 0.1 V) are characterized in this paper. Based on 88 devices, the impact of the low subthreshold swing on the overall performance is studied. Furthermore, correlation between parameters that are important for device characterization is determined.
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| 70. |
- Memisevic, Elvedin, et al.
(författare)
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Individual Defects in InAs/InGaAsSb/GaSb Nanowire Tunnel Field-Effect Transistors Operating below 60 mV/decade
- 2017
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984.
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Tidskriftsartikel (refereegranskat)abstract
- Tunneling field-effect transistors (TunnelFET), a leading steep-slope transistor candidate, is still plagued by defect response, and there is a large discrepancy between measured and simulated device performance. In this work, highly scaled InAs/InxGa1−xAsySb1‑y/GaSb vertical nanowire TunnelFET with ability to operate well below 60 mV/decade at technically relevant currents are fabricated and characterized. The structure, composition, and strain is characterized usingtransmission electron microscopy with emphasis on the heterojunction. Using Technology Computer Aided Design (TCAD) simulations and Random Telegraph Signal (RTS) noise measurements, effects of different type of defects are studied. The study reveals that the bulk defects have the largest impact on the performance of these devices, although for these highly scaled devices interaction with even few oxide defects can have large impact on the performance. Understanding the contribution by individual defects, as outlined in this letter, is essential to verify the fundamental physics of device operation, and thus imperative for taking the III−V TunnelFETs to the next level.
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