| 21. |
- Fellström, Bengt, 1947-, et al.
(författare)
-
Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
- 2019
-
Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 40:2, s. 71-74
-
Tidskriftsartikel (refereegranskat)abstract
- There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.
|
|
| 22. |
- Franken, Matthias K., et al.
(författare)
-
Does passive sound attenuation affect responses to pitch-shifted auditory feedback?
- 2019
-
Ingår i: The Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966. ; 146:6, s. 4108-4121
-
Tidskriftsartikel (refereegranskat)abstract
- The role of auditory feedback in vocal production has mainly been investigated by altered auditory feedback (AAF) in real time. In response, speakers compensate by shifting their speech output in the opposite direction. Current theory suggests this is caused by a mismatch between expected and observed feedback. A methodological issue is the difficulty to fully isolate the speaker’s hearing so that only AAF is presented to their ears. As a result, participants may be presented with two simultaneous signals. If this is true, an alternative explanation is that responses to AAF depend on the contrast between the manipulated and the non-manipulated feedback. This hypothesis was tested by varying the passive sound attenuation (PSA). Participants vocalized while auditory feed- back was unexpectedly pitch shifted. The feedback was played through three pairs of headphones with varying amounts of PSA. The participants’ responses were not affected by the different levels of PSA. This suggests that across all three headphones, PSA is either good enough to make the manipulated feedback dominant, or differences in PSA are too small to affect the contribution of non-manipulated feedback. Overall, the results suggest that it is important to realize that non-manipulated auditory feedback could affect responses to AAF.
|
|
| 23. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
|
|
| 24. |
- Geschwind, Lars, 1970-, et al.
(författare)
-
The Changing Roles of Academic Leaders : Decision-Making, Power, and Performance
- 2019. - 1
-
Ingår i: Reforms, Organizational Change and Performance in Higher Education. - Cham : Palgrave Macmillan. - 9783030117382 - 9783030117375 ; , s. 181-210
-
Bokkapitel (refereegranskat)abstract
- Major reforms in the Nordic countries have increased the formal autonomy of higher education institutions (HEIs) to make decisions over their own activities, both academic core tasks and managerial/administrative activities. The issue addressed in this chapter is how these changes have affected the role of the academic leader. Across the four countries, we see clear signs of change regarding academic leadership comprising a mix of institutional logics in the interviews: the professional, collegial traditional academic leadership, which is based on rotating systems, election among peers, and collegial decision-making, has been complemented with, and in some places replaced by, a managerial logic with top-down order-giving, performance measurement and appointed managers as a new academic profession. Another related general trend is the greater focus on individual managers. The analysis also shows that Denmark and Finland are the countries that lead the way when it comes to increasing the formal authority of managers. The introduction of appointed managers rather than elected ones has altered the way HEIs operate in these two countries. However, as this chapter has shed light on, management reform has not been implemented in the same depth and with the same pace across and within universities.
|
|
| 25. |
- Hagstrom, Emil, et al.
(författare)
-
IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
-
Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
|
|
| 26. |
|
|
| 27. |
- Hellenbrand, Markus, et al.
(författare)
-
Comparison of Low-Frequency Noise in Nanowire and Planar III-V MOSFETs
- 2019
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We compare III-V nanowire (NW) metal-oxidesemiconductor field-effect transistors (MOSFETs) in a vertical gate-all-around (GAA) as well as a lateral trigate architecture with planar reference MOSFETs and reveal that the NW geometry does not deteriorate the low-frequency noise (LFN) performance. In fact, with gate oxides deposited at the same conditions, the NW structures show potential to achieve better metrics due to slightly lower border trap densities Nbt. The normalized LFN in transistors with a higher number of NW can degrade due to averaging effects between individual nanowires within the same device.
|
|
| 28. |
- Hellenbrand, Markus, et al.
(författare)
-
Low-Frequency Noise in Nanowire and Planar III-V MOSFETs
- 2019
-
Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317.
-
Tidskriftsartikel (refereegranskat)abstract
- Nanowire geometries are leading contenders for future low-power transistor design. In this study, low-frequency noise is measured and evaluated in highly scaled III-V nanowire metal-oxide-semiconductor field-effect transistors (MOSFETs) and in planar III-V MOSFETs to investigate to what extent the device geometry affects the noise performance. Number fluctuations are identified as the dominant noise mechanism in both architectures. In order to perform a thorough comparison of the two architectures, a discussion of the underlying noise model is included. We find that the noise performance of the MOSFETs in a nanowire architecture is at least comparable to the planar devices. The input-referred voltage noise in the nanowire devices is superior by at least a factor of four.
|
|
| 29. |
- Henriksson, Peter, et al.
(författare)
-
Microvascular capillary assessment in relation to forearm blood flow
- 2019
-
Ingår i: Clinical Physiology and Functional Imaging. - : WILEY. - 1475-0961 .- 1475-097X. ; 39:5, s. 322-326
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. Methods Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. Results This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0 center dot 57; P<0 center dot 05). Conclusions Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.
|
|
| 30. |
- Hober, Andreas, et al.
(författare)
-
Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay
- 2019
-
Ingår i: Molecular & Cellular Proteomics. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 1535-9476 .- 1535-9484. ; 18:12, s. 2433-2446
-
Tidskriftsartikel (refereegranskat)abstract
- Stable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released on trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently used to investigate the effects of omega-3 carboxylic acids (OM3-CA) and fenofibrate on these 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECT I (NCT02354976). No significant changes were observed in the OM3-CA arm, whereas treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies. Applications of LC-SRM in clinical research are still limited. SIS PrEST are a novel class of standards added prior to trypsinization. We have developed a semi-automated sample preparation workflow and a SIS PrEST LC-SRM/MS Tier 2 assay for absolute quantification of 13 apolipoproteins in human plasma and applied it on clinical samples from the EFFECT I study. We demonstrate, for the first time, that SIS PrEST can be applied for exploratory biomarker research in clinical settings and capture drug effects.
|
|
