| 2021. |
- Tossavainen, Erik, 1977-
(författare)
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In the hands of ohm : hemodynamic aspects in pulmonary hypertension
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congestive heart failure (CHF) is one of the most challenging diseases in terms of health care demand and mortality, in the western world. Despite major breakthroughs in the fields of diagnosis and treatment over the three last decades, the management of CHF still remains challenging.CHF is defined as inability of the heart to supply sufficient blood flow to meet the needs of the body. This definition however, may be an oversimplification of a complex pathophysiological process since patients with overt CHF may have normal, or even supernormal cardiac output at the expense of increased filling pressures, which subsequently leads to the development of post capillary pulmonary hypertension (PH). In the presence of advanced CHF, clinical signs and symptoms are obvious at rest. However, the majority of affected individuals do not experience any discomfort at rest and may demonstrate normal findings when assessed. Small increases in systemic blood pressure and or venous return, caused by activity may result in severe elevation of filling pressures if left ventricular compliance is significantly decreased. This example highlights the need to perform cardiac investigations during stress to provoke symptoms. Increased pulmonary vascular resistance (PVR), commonly found in pre-capillary PH, is a condition that shares many symptoms with CHF, and is also associated with poor prognosis. Even though the disease is located within the lung vessels, it is highly important and challenging task differentiating pre- and post-capillary PH. Since treatment differs considerably and may be detrimental in case of misdiagnosis, additional sensitive and reliable screening methods are crucial to aid in differentiation.Methods: Out of the four studies included in this thesis, three were conducted solely at Norrland’s University Hospital, while patients in the third study were recruited and examined at Uppsala Akademiska Hospital. All included patients had idiopathic dyspnea and were admitted for right heart catheterization (RHC), which is gold standard with regards to hemodynamics. Echocardiographic examinations were performed simultaneously with RHC, except in the Uppsala study, wherein echocardiography were performed within 3 days to the RHC.Echo-Doppler derived pulmonary artery acceleration time (PAcT) is an easily assessed parameter, indicating elevated pulmonary artery systolic pressure (PASP) and pulmonary artery resistance (PVR). PAcT was tested as a screening method for identification and differentiation of pre and post- capillary PH in a cohort of 56 patients (study 1).The ability to calculate PVR non-invasively, using novel echocardiographic measurements, was made by replacing the invasive pressure and flow components that constitutes the foundation of the PVR = (mean pulmonary artery pressure – Pulmonary capillary wedge pressure (PCWP)) /cardiac output), with novel echocardiographic measurements. PVR = mPAP-Chemla – Left atrial strain rate during atrial systole (LASRa) / Cardiac Output-Echo (study 2).Invasively measured left ventricular filling pressure in response to passive leg lifting, and its ability to predict pathological increase in left ventricular filling pressures during supine bicycling, was tested in a population of 85 patients with normal left ventricular ejection fraction (LVEF) and suspicion of CHF based on NT-proBNP levels alone were investigated (Study 3).Finally, an evaluation of standard and novel Doppler echocardiographic parameters, potentially useful in identifying patients who may develop increased filling pressures during passive leg lifting (PLL), was carried out (study 4).Results:Study 1: PAcT correlated negatively with pulmonary artery systolic pressure (PASP) (r = -0.60, p < 0.001) and PVR (r = -0.57, p < 0.001). PAcT of <90 ms had a sensitivity of 84% and a specificity of 85% in identifying patients with PVR ≥ 3.0 WU. Regardless of normal or elevated left sided filling pressures, PAcT differed significantly in patients with normal, compared to those with elevated levels of, PVR (p < 0.01). A significant difference was also found on comparison of the PAcT/PASP ratio (p < 0.01), with a lower ratio among patients with PVR ≥ 3.0. WU.Study 2: We prospectively used Doppler and 2D echocardiography in 46 patients with sinus rhythm which revealed that left atrial strain rate during atrial systole (LASRa) had the highest significant positive correlation with PCWP (r2 = 0.65, P < 0.001). By adopting a linear line of best-fit, LASRa may therefore be substituted for PCWP. Subsequently, LASRa was substituted into the PVR equation. This novel echocardiographically derived PVR calculation, significantly correlated with RHC generated PVR values (r2 = 0.69, P < 0.001) and minor drift (+0.1WU) when assessed by Bland Altman analysis.Study 3: Only 22% (11/51) of patients with elevated NT-proBNP had PCWP above normal levels at rest. However, in response to PLL, 47% of patients developed elevated PCWP, and the majority of this 47% subsequently developed pathological pressure levels while performing supine cycling exercise. Thus, the likelihood of developing high LVFPs during exercise could be determined by PLL, with a sensitivity and specificity of 90%.Study 4: At rest, left atrial volume indexed to body mass index (BMI) (LAVI) and mitral deceleration time (DT) were independently related to PCWP during PLL. However, during PLL univariate regression analysis revealed LASRa (β = -0.77, P <0,001) and E/LVSRe (β = 0.47, P < 0,021) most related to PCWPPLL. Multiple regression analysis fortified LASRa and E/LVSRe as relevant independent parameters useful in the assessment of filling pressure during PLL.Conclusion: A PAcT < 90ms is strongly suggestive of increased PVR (>3.0 WU). Based on study 1, there is clear evidence suggesting that these findings apply irrespective of LVFPs. PAcT can potentially serve as a rapid screening tool for estimation of PVR, however, is not useful if the exact level of PVR is required. In this case, an established PVR calculation method is preferred, and could be performed with higher precision by inclusion of echocardiography derived LASRa as a surrogate measure of PCWP. Insufficient LV compliance results in the inability to cope with increased cardiac preload. Nt-proBNP is secreted when the myocardium is stretched, however only a small portion of patients within the CHF group (study 3) had a high PCWP at rest. Nearly half of the study population with elevated NT-proBNP showed increased PCWP during PLL, which is indicative of underlying ventricular stiffness. By performing this preload increasing maneuver, patients predisposed to developing high filling pressure during supine cycling could be identified with high sensitivity and specificity. Echocardiography, in comparison with RHC, is more accessible, safer and requires less resources and time, thus is an appealing option in the quest to identify additional, non-invasive methods reflective of invasive pressures, which could be useful in the assessment of filling pressure during different loading conditions. LAVI at rest, LASRa and E/LVSRe during PLL, proved independently related to PCWP during PLL.
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| 2022. |
- Tran, Anh Nhi, et al.
(författare)
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Impact on affected families and society of severe rotavirus infections in Swedish children assessed in a prospective cohort study.
- 2018
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Ingår i: Infectious Diseases. - : Taylor & Francis Group. - 2374-4235 .- 2374-4243. ; 50:5, s. 361-371
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few prospective cohort studies have estimated the overall impact of severe rotavirus gastroenteritis (RVGE) leading to hospitalization on families and society. We assessed human and economic resources needed to care for an affected average child aged <5 years in Sweden.METHODS: The study was conducted in Astrid Lindgren Children's Hospital which serves approximately 14% of all Swedish children <5 years of age. All children admitted with acute gastroenteritis in the study period were tested for rotavirus. Health care consumption was collected prospectively and publically available unit costs used to calculate direct costs. Non-medical and indirect costs were collected in interviews with families using a standardized questionnaire during the hospital stay and approximately 14 days post-discharge.RESULTS: 144/206 children (70%) with laboratory-confirmed RVGE were included. The median age was 14 months. The average total cost per hospitalized child was €3894, of which €2169 (56%) was due to direct healthcare-related costs (including Emergency Department visits and in-patient care), €104 (2%) to non-medical direct costs and €1621 (42%) to indirect costs due to productivity loss. Carers of children with severe RVGE were absent from work on average five days per study child: four days during hospitalization of affected child and one day due to gastroenteritis in the carer.CONCLUSIONS: Costs for RVGE are dominated by direct costs which are similar to some other countries in Europe, but indirect costs due to productivity loss are also important, and should be considered in decisions to introduce rotavirus vaccines into national vaccination programmes.
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| 2023. |
- Trenkwalder, Teresa, et al.
(författare)
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Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.
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| 2024. |
- Trinh, Thang, et al.
(författare)
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Background risk of breast cancer and the association between physical activity and mammographic density
- 2015
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Ingår i: Breast Cancer Research. - : BIOMED CENTRAL LTD. - 1465-5411 .- 1465-542X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction High physical activity has been shown to decrease the risk of breast cancer, potentially by a mechanism that also reduces mammographic density. We tested the hypothesis that the risk of developing breast cancer in the next 10 years according to the Tyrer-Cuzick prediction model influences the association between physical activity and mammographic density. Methods We conducted a population-based cross-sectional study of 38,913 Swedish women aged 4074 years. Physical activity was assessed using the validated web-questionnaire Active-Q and mammographic density was measured by the fully automated volumetric Volpara method. The 10-year risk of breast cancer was estimated using the Tyrer-Cuzick (TC) prediction model. Linear regression analyses were performed to assess the association between physical activity and volumetric mammographic density and the potential interaction with the TC breast cancer risk. Results Overall, high physical activity was associated with lower absolute dense volume. As compared to women with the lowest total activity level (<40 metabolic equivalent hours [MET-h] per day), women with the highest total activity level (>= 50 MET-h/day) had an estimated 3.4 cm(3) (95% confidence interval, 2.3-4.7) lower absolute dense volume. The inverse association was seen for any type of physical activity among women with <3.0% TC 10-year risk, but only for total and vigorous activities among women with 3.0-4.9% TC risk, and only for vigorous activity among women with >= 5.0% TC risk. The association between total activity and absolute dense volume was modified by the TC breast cancer risk (P-interaction = 0.05). As anticipated, high physical activity was also associated with lower non-dense volume. No consistent association was found between physical activity and percent dense volume. Conclusions Our results suggest that physical activity may decrease breast cancer risk through reducing mammographic density, and that the physical activity needed to reduce mammographic density may depend on background risk of breast cancer.
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| 2025. |
- Tsavalas, P., et al.
(författare)
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Be ITER-like wall at the JET tokamak under plasma
- 2017
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T170
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Tidskriftsartikel (refereegranskat)abstract
- The JET tokamak is operated with beryllium and tungsten plasma-facing components to prepare for the exploitation of ITER. To determine beryllium erosion and migration in JET a set of markers were installed. Specimens from different beryllium marker tiles of the main wall of the ITER-like wall (ILW) JET tokamak from the first and the second D-D campaign were analyzed with nuclear reaction analysis, x-ray fluorescence spectroscopy, scanning electron microscopy and x-ray diffraction (XRD). Emphasis was on the determination of carbon plasma impurities deposited on beryllium surfaces. The C-12(d, p(0))C-13 reaction was used to quantify carbon deposition and to determine depth profiles. Carbon quantities on the surface of the Be tiles are low, varying from (0.35 +/- 0.07) x 10(17) to (11.8 +/- 0.6) x 10(17) at cm(-2) in the deposition depth from 0.4 to 6.7 mu m, respectively. In the 0.4-0.5 mm wide grooves of castellation sides the carbon content is found up to (14.3 +/- 2.5) x 10(17) at cm(-2) while it is higher (up to (38 +/- 4) x 10(17) at cm(-2)) in wider gaps (0.8 mm) separating tile segments. Oxygen (O), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni) and tungsten (W) were detected in all samples exposed to plasma and the reference one but at lower quantities at the latter. In the central part of the Inner Wall Guard Limiter from the first ILW campaign and in the Outer Poloidal Limiter from the second ILW campaign the Ni interlayer has been completely eroded. XRD shows the formation of BeNi in most specimens.
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| 2026. |
- Tseggai, M, et al.
(författare)
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Nuclear structure and magnetic properties of perovskite compounds La1−xNdxFe0.5Cr0.5O3 (x = 0.1, 0.15 and 0.2)
- 2008
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 458:1-2, s. 372-377
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Tidskriftsartikel (refereegranskat)abstract
- Perovskite oxides with the composition La1−xNdxFe0.5Cr0.5O3 (x = 0.10, 0.15 and 0.20) have been studied. The samples have been prepared using the standard solid-state reaction method in air. The X-ray and neutron diffractograms indicates that the samples crystallize in the orthorhombic perovskite structure with space group Pnma (No. 62). The Nd-substitution causes minor changes in the cell parameters and bond lengths but the nuclear structure remains orthorhombic in the whole range of substitutions and in the temperature range of 10–700 K. The magnetic structure of the samples at room temperature and below is G-type antiferromagnetic with an average magnetic moment of the Fe/Cr ions of 3.29(3) μB/atom at 10 K independent of the Nd content. At room temperature the average magnetic moment of the Fe/Cr ions reduces to 1.23 μB/atom. At temperatures below 250 K a weak but increasing uncompensated spontaneous magnetic moment develops that reaches a magnitude of about 0.5 emu/g (or 0.02 μB per Fe/Cr site) at 10 K. This moment saturates rather rapidly in the magnetization versus magnetic field curve and is at higher field superposed on the response of the antiferromagnetic spin system.
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| 2027. |
- Tsoi, Lam C., et al.
(författare)
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Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size amp;gt;39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.
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| 2028. |
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Tuning the Emission Energy of Chemically Doped Graphene Quantum Dots
- 2016
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Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Tuning the emission energy of graphene quantum dots (GQDs) and understanding the reason of tunability is essential for the GOD function in optoelectronic devices. Besides material-based challenges, the way to realize chemical doping and band gap tuning also pose a serious challenge. In this study, we tuned the emission energy of GQDs by substitutional doping using chlorine, nitrogen, boron, sodium, and potassium dopants in solution form. Photoluminescence data obtained from (Cl- and N-doped) GQDs and (B-, Na-, and K-doped) GQDs, respectively exhibited red- and blue-shift with respect to the photoluminescence of the undoped GQDs. X-ray photoemission spectroscopy (XPS) revealed that oxygen functional groups were attached to GQDs. We qualitatively correlate red-shift of the photoluminescence with the oxygen functional groups using literature references which demonstrates that more oxygen containing groups leads to the formation of more defect states and is the reason of observed red-shift of luminescence in GQDs. Further on, time resolved photoluminescence measurements of Cl- and N-GQDs demonstrated that Cl substitution in GQDs has effective role in radiative transition whereas in N-GQDs leads to photoluminescence (PL) quenching with non-radiative transition to ground state. Presumably oxidation or reduction processes cause a change of effective size and the bandgap.
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| 2029. |
- Tuominen, Rainer, et al.
(författare)
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The Role of Germline Alterations in the DNA Damage Response Genes BRIP1 and BRCA2 in Melanoma Susceptibility
- 2016
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley-Blackwell. - 1045-2257 .- 1098-2264. ; 55:7, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology.
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| 2030. |
- Törnquist, Per, et al.
(författare)
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On the use of dated sediments to investigate historical nuclear discharges
- 2023
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Ingår i: Marine Pollution Bulletin. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0025-326X .- 1879-3363. ; 188
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Forskningsöversikt (refereegranskat)abstract
- Studsvik, a Swedish nuclear research facility, has been releasing aquatic radioactive discharges in the Baltic Sea, through the bay Tva center dot ren, since 1959. The permissible discharge levels are regulated by the Swedish Radiation Safety Authority (SSM) but only information about 60Co, 137Cs, 152Eu, total alpha and beta activities were re-ported up to 2002. Since then, the reports cover most a more comprehensive set of radionuclides. In this context, the seabed can be utilized as a chronological archive to investigate historical Studsvik releases. To this end, 23 sediment cores covering the whole area of the bay were studied and 5 of them were dated using 210Pb-dating methods. Since the discharges from Studsvik contain both plutonium and caesium, neither can be used to validate the 210Pb-dating method. Instead, stable lead with maximum deposition, known to be dated to 1970, was used. Cobalt-60, 137Cs, and 152Eu depth distributions were studied from the dated sediment cores and compared with reported levels of aquatic discharges. The expected sediment 137Cs-peak from the fallout from the Chornobyl accident was however smeared out, indicating an ongoing inflow of 137Cs with the Baltic seawater. Our findings show that reported releases of aquatic discharges of 60Co and 152Eu are consistent with measured sediment activity distribution. The sediments from the deepest parts of Tva center dot ren, with intact chronology and with a high time resolution, are ideal for investigating historical nuclear discharges and can be a tool to investigate unreported radionuclide releases. Dated sediment can in this way be a tool for nuclear safeguards to evaluate past and present activities in nuclear facilities.
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