| 51. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
-
Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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| 52. |
- Bruce, Michael G, et al.
(författare)
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International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005
- 2008
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Ingår i: Emerging Infectious Diseases. - Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 14:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.
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| 53. |
- Bylund, Annika, et al.
(författare)
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Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.
- 2005
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Ingår i: Experimental biology and medicine. - 1535-3702 .- 1535-3699. ; 230:3, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.
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| 54. |
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| 55. |
- Celsius, Anders, 1701-1744
(författare)
-
Character chronologicus Newtonianus, quem, ex consensu ampliss. ord. philosoph. regiae academiae Upsaliensis, praeside ... Andrea Celsio ... ad diem XI Junii, MDCCXLIII. horis, ante meridiem, solitis, in auditorio Gustav. majori, dissertatione graduali, enucleatum, publice examinandum sistit Andreas Haquini Neander, Smolandus.
- 1743
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 56. |
- Celsius, Anders, 1701-1744
(författare)
-
Dissertatio academica, de universalitate diluvii Noachici, quam, consentiente ampliss. facult. philosoph. in regia acad. Upsaliensi, præside ... Andrea Celsio ... publicæ bonorum disquisitioni modeste submittit alumnus Kohreanus Andreas Hallenberg, Smolandus, in audit. Gust. maj. ad diem 10 Maji, MDCCXXXVIIII. Horis, ante meridiem, solitis.
- 1738
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 57. |
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| 58. |
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| 59. |
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| 60. |
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| 61. |
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| 62. |
- Chapman, Ben, et al.
(författare)
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A foraging cost of migration for a partially migratory cyprinid fish
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Migration has evolved as a strategy to maximise individual fitness in response to seasonally changing ecological and environmental conditions. However, migration can also incur costs, and quantifying these costs can provide important clues to the ultimate ecological forces that underpin migratory behaviour. A key emerging model to explain migration in many systems posits that migration is driven by seasonal changes to a predation/growth potential (p/g) trade-off that a wide range of animals face. In this study we assess a key assumption of this model for a common cyprinid partial migrant, the roach Rutilus rutilus, which migrates from shallow lakes to streams during winter. By sampling fish from stream and lake habitats in the autumn and spring and measuring their stomach fullness and diet composition, we tested if migrating roach pay a cost of reduced foraging when migrating. Resident fish had fuller stomachs containing more high quality prey items than migrant fish. Hence, we document a feeding cost to migration in roach, which adds additional support for the validity of the p/g model of migration in freshwater systems.
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| 63. |
- Chemtob, Raphaelle A., et al.
(författare)
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Stroke in acute type A aortic dissection : the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD)
- 2020
-
Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 58:5, s. 1027-1034
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients. METHODS: The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014. RESULTS: Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P < 0.001), syncope (30.6% vs 17.6%, P < 0.001), cardiogenic shock (33.1% vs 20.7%, P < 0.001) and pericardial tamponade (25.9% vs 14.7%, P < 0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P = 0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P < 0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P < 0.001). CONCLUSIONS: Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
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| 64. |
- Chemtob, Raphaelle A, et al.
(författare)
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Stroke in acute type A aortic dissection: the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD).
- 2020
-
Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - 1873-734X. ; 58:5, s. 1027-1034
-
Tidskriftsartikel (refereegranskat)abstract
- Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients.The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014.Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P<0.001), syncope (30.6% vs 17.6%, P<0.001), cardiogenic shock (33.1% vs 20.7%, P<0.001) and pericardial tamponade (25.9% vs 14.7%, P<0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P=0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P<0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P<0.001).Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
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| 65. |
- Chernogubova, Ekaterina, et al.
(författare)
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Common and Low-Frequency Genetic Variants in the PCSK9 Locus Influence Circulating PCSK9 Levels
- 2012
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 32:6, s. 1526-1534
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Tidskriftsartikel (refereegranskat)abstract
- Objective- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that influences plasma low-density lipoprotein concentration and susceptibility to coronary heart disease. Circulating PCSK9 levels show considerable interindividual differences, but the factors responsible for this variation are largely unknown. Methods and Results- We analyzed circulating PCSK9 levels in 4 cohorts of healthy, middle-aged Swedes (n=5722) and found that PCSK9 levels varied over approximate to 50-fold range, showed a positive relationship with plasma low-density lipoprotein-cholesterol concentration, and were associated with plasma triglyceride, fibrinogen, insulin, and glucose concentrations. A genome-wide association study conducted in 2 cohorts (n=1215) failed to uncover common genetic variants robustly associated with variation in circulating PCSK9 level. As expected, the minor allele of the PCSK9 R46L variant was in all cohorts associated with reduced PCSK9 levels and decreased plasma low-density lipoprotein-cholesterol concentrations, but no relationship was observed with the plasma triglyceride concentration. Further mapping of the PCSK9 locus revealed a common polymorphism (rs2479415, minor allele frequency 43.9%), located approximate to 6 kb upstream from PCSK9, which is independently associated with increased circulating PCSK9 levels. Conclusion- Common and low-frequency genetic variants in the PCSK9 locus influence the pronounced interindividual variation in circulating PCSK9 levels in healthy, middle-aged white (predominantly Swedish) subjects.
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| 66. |
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| 67. |
- Dijken, Jan W.V. van, 1947-, et al.
(författare)
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Samarbete breddar forskning : Oral Biomaterialgruppen, Umeå
- 2008
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Ingår i: Tandläkartidningen. - : Sveriges Tandläkarförbund. ; 100:5, s. 74-79
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Vid institutionen för odontologi vid Umeå Universitet finns en lång tradition av biomaterialforskning. För drygt två år sedan samlades större delen av den forskningen i ett vetenskapligt nätverk. Här beskrivs ett axplock av det breda forskningsarbetet.
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| 68. |
- Elowsson, Anders
(författare)
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Modeling Music : Studies of Music Transcription, Music Perception and Music Production
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation presents ten studies focusing on three important subfields of music information retrieval (MIR): music transcription (Part A), music perception (Part B), and music production (Part C).In Part A, systems capable of transcribing rhythm and polyphonic pitch are described. The first two publications present methods for tempo estimation and beat tracking. A method is developed for computing the most salient periodicity (the “cepstroid”), and the computed cepstroid is used to guide the machine learning processing. The polyphonic pitch tracking system uses novel pitch-invariant and tone-shift-invariant processing techniques. Furthermore, the neural flux is introduced – a latent feature for onset and offset detection. The transcription systems use a layered learning technique with separate intermediate networks of varying depth. Important music concepts are used as intermediate targets to create a processing chain with high generalization. State-of-the-art performance is reported for all tasks.Part B is devoted to perceptual features of music, which can be used as intermediate targets or as parameters for exploring fundamental music perception mechanisms. Systems are proposed that can predict the perceived speed and performed dynamics of an audio file with high accuracy, using the average ratings from around 20 listeners as ground truths. In Part C, aspects related to music production are explored. The first paper analyzes long-term average spectrum (LTAS) in popular music. A compact equation is derived to describe the mean LTAS of a large dataset, and the variation is visualized. Further analysis shows that the level of the percussion is an important factor for LTAS. The second paper examines songwriting and composition through the development of an algorithmic composer of popular music. Various factors relevant for writing good compositions are encoded, and a listening test employed that shows the validity of the proposed methods.The dissertation is concluded by Part D - Looking Back and Ahead, which acts as a discussion and provides a road-map for future work. The first paper discusses the deep layered learning (DLL) technique, outlining concepts and pointing out a direction for future MIR implementations. It is suggested that DLL can help generalization by enforcing the validity of intermediate representations, and by letting the inferred representations establish disentangled structures supporting high-level invariant processing. The second paper proposes an architecture for tempo-invariant processing of rhythm with convolutional neural networks. Log-frequency representations of rhythm-related activations are suggested at the main stage of processing. Methods relying on magnitude, relative phase, and raw phase information are described for a wide variety of rhythm processing tasks.
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| 69. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 70. |
- Fengsrud, Espen, 1970-, et al.
(författare)
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Total endoscopic ablation of patients with long-standing persistent atrial fibrillation : a randomized controlled study
- 2016
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - Oxford, United Kingdom : Oxford University Press. - 1569-9293 .- 1569-9285. ; 23:2, s. 292-298
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Total endoscopic ablation of atrial fibrillation is an alternative to catheter ablation, but its clinical role needs further evaluation. The aim of this study was to compare total endoscopic ablation with rate control in patients with long-standing persistent atrial fibrillation and to examine the effect of endoscopic ablation on heart rhythm, symptoms, physical working capacity and myocardial function during 1 year of follow-up.Methods: In a prospective controlled study, 36 patients aged >50 years with symptomatic long-standing persistent atrial fibrillation were randomized to either total endoscopic ablation (n = 17, after two drop-outs before ablation n = 15) or rate control therapy (n = 19). In the ablation group, a box lesion encircling the pulmonary veins was performed, using temperature-controlled radiofrequency energy. Loop recorders were implanted in all patients. Echocardiography and quality-of-life assessment were performed at 6 and 12 months, and physical working capacity assessment at 6 months.Results: There was no mortality or thromboembolic event. In the control group, all patients were in permanent atrial fibrillation during 12 months of follow-up. In the ablation group, the proportion of patients in sinus rhythm without antiarrhythmic drugs was 12/15 (80%) at 12 months. The median freedom of atrial fibrillation at 3-12 months was 95% in the ablation group and the proportion of patients with an atrial fibrillation burden of <5% at 3-12 months was 8/15 (53%). The left ventricular ejection fraction increased during follow-up in the ablation group compared with the control group (from 53.7 ± 8.6 to 58.8 ± 6.5%, P = 0.003), combined with a reduction in the left atrial area (from 29.2 ± 5.5 to 27.2 ± 6.3 cm(2), P = 0.002). The physical working capacity increased in the ablation group compared with the control group (from 94 ± 21.4 to 102.9 ± 14.4%, P = 0.011). The subjective physical and mental capacity scale also improved during follow-up in the ablation group, but not in the control group (P =0.003 and 0.018, respectively).Conclusions: Total endoscopic ablation in patients with long-standing persistent atrial fibrillation significantly reduced atrial fibrillation burden 12 months after intervention compared with controls. The left ventricular function, physical working capacity and subjective physical and mental health were improved. These results need to be confirmed in larger randomized trials.
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| 71. |
- Folkersen, Lasse, et al.
(författare)
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Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease
- 2010
-
Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 3:4, s. 365-373
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. METHODS AND RESULTS: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. CONCLUSIONS: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
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| 72. |
- Folkersen, Lasse, et al.
(författare)
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Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease
- 2017
-
Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.
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| 73. |
- Folkersen, Lasse, et al.
(författare)
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Unraveling Divergent Gene Expression Profiles in Bicuspid and Tricuspid Aortic Valve Patients with Thoracic Aortic Dilatation: The ASAP Study
- 2011
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Ingår i: Molecular Medicine. - : Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 17:11-12, s. 1365-1373
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Tidskriftsartikel (refereegranskat)abstract
- Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (less than4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.
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| 74. |
- Frank, Catharina, 1961-, et al.
(författare)
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Ethics rounds in the ambulance service: a qualitative evaluation
- 2024
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Ingår i: BMC Medical Ethics. - : Springer Nature. - 1472-6939. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is a common ethical challenge for ambulance clinicians to care for patients with impaired decision-making capacities while assessing and determining the degree of decision-making ability and considering ethical values. Ambulance clinicians’ ethical competence seems to be increasingly important in coping with such varied ethical dilemmas. Ethics rounds is a model designed to promote the development of ethical competence among clinicians. While standard in other contexts, to the best of our knowledge, it has not been applied within the ambulance service context. Thus, the aim of this study was to describe ambulance clinicians’ experiences of participating in ethics rounds.MethodsThis was a qualitative descriptive study, evaluating an intervention. Data were collected through sixteen interviews with ambulance clinicians who had participated in an intervention involving ethics rounds. The analysis was performed by use of content analysis.ResultsTwo themes describe the participants’ experiences: (1) Reflecting freely within a given framework, and (2) Being surprised by new insights. The following categories form the basis of the themes; 1a) Gentle guidance by the facilitator, 1b) A comprehensible structure, 2a) New awareness in the face of ethical problems, and 2b) Shared learning through dialogue.ConclusionIncorporating structured ethics rounds seems to create a continuous development in ethical competence that may improve the quality of care in the ambulance service. Structured guidance and facilitated group reflections offer ambulance clinicians opportunities for both personal and professional development. An important prerequisite for the development of ethical competence is a well-educated facilitator. Consequently, this type of ethics rounds may be considered a useful pedagogical model for the development of ethical competence in the ambulance service.
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| 75. |
- Geirsson, Arnar, et al.
(författare)
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Differential outcomes of open and clamp-on distal anastomosis techniques in acute type A aortic dissection
- 2019
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:5, s. 1750-1758
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique.Methods: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014.Results: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% +/- 4.4%) compared with the open-distal group (73.0% +/- 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival.Conclusions: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short-and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases.
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| 76. |
- Gertow, Karl, et al.
(författare)
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Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
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Tidskriftsartikel (refereegranskat)abstract
- Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
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| 77. |
- Glimskär, Anders, et al.
(författare)
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Utveckling av flygbildsmetodik och indikator för åkermarkens arrondering
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport beskriver underlag och möjligheter till presentation av resultat för en ny miljömålsindikator som kan följa utvecklingen för åkermarkens arrondering (form och storlek). Indikatorn baseras på mätningar av åkermarkens kantlängd och areal, och kan användas för att beskriva åkermarkens förekomst, förändringar i brukande, förutsättningarna för förekomst av småbiotoper och därmed den biologiska mångfalden.Inom projektet har vi testat en metodik för avgränsning av åkermark i flygbilder från olika tider som underlag för att uppskatta förändringar. Testområde var de län som ingår i regional miljöövervakning via NILS, ”LillNILS”. Det stickprov som LillNILS har verkar vara funktionellt för att påvisa förändringar över tiden, för grupper av län. En dialog bör föras med Jordbruksverket om hur Blockdatabasen kan göras mer användbar och lättanvänd för denna typ av sammanställningar. Innan det är gjort är det svårt att göra en realistisk uppskattning av hur genomförbart det skulle vara med en uppföljning enbart baserad på Blockdatabasen.Utredningen betonar vikten av att skilja på olika typer av kanter för möjligheten att tolka förändringar, exempelvis kanter mellan två åkermarksytor och kanter mot annan mark. Redan i en grundinventering bör man kartera ”tidigare åkermark” (med begynnande igenväxning), eftersom de kanterna är föränderliga och av annan karaktär än övriga.Metodiken för flygbildsinventering av åkerkanter bör ha tydliga definitioner och stor noggrannhet för att resultaten ska bli användbara för att belysa detaljförändringar, eftersom det kan ge stora skillnader i slutresultatet. För bakåtdatering i äldre flygbilder bör man redan från början ta in alla tidsskikt i arbetet, först det äldsta tidsskiktet och därefter jobba sig framåt i tiden.Rapporten innehåller också kostnadsuppskattningar för både bakåtdatering i äldre flygbilder och fortlöpande uppföljning av förändringar framåt i tiden. Eftersom det förstnämnda är en stor engångsinvestering, föreslår vi att den i huvudsak bör initieras och finansieras nationellt.
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| 78. |
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| 79. |
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| 80. |
- Granholm, Anders, et al.
(författare)
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Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48:1, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
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| 81. |
- Granholm, Anders, et al.
(författare)
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Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
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| 82. |
- Granholm, Anders, et al.
(författare)
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Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
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| 83. |
- Grubb, Anders, et al.
(författare)
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Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator
- 2014
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 60:7, s. 974-986
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays.METHODS:Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR.RESULTS:We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C.CONCLUSIONS:A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.
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| 84. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia
- 2018
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:10, s. 2117-2125
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.
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| 85. |
- Gustafsson, Torfinn, et al.
(författare)
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Authors' response
- 2023
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Ingår i: Journal of Forensic Sciences. - : John Wiley & Sons. - 0022-1198 .- 1556-4029. ; 68:3, s. 1086-1088
-
Tidskriftsartikel (refereegranskat)
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| 86. |
- Gustafsson, Torfinn, et al.
(författare)
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The utility of histology in assessing the cause of death in medico-legal autopsies in selected trauma deaths : suspension-, immersion-, fire-, and traffic-related
- 2023
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Ingår i: Journal of Forensic Sciences. - : John Wiley & Sons. - 0022-1198 .- 1556-4029. ; 68:2, s. 509-517
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Tidskriftsartikel (refereegranskat)abstract
- The goal of a medico-legal autopsy is primarily to determine the cause and manner of death. To this end, the pathologist often uses auxiliary analyses, including histology. However, the utility of routine histology in all medico-legal autopsies is unknown. Earlier studies on the utility of routine histology have shown inconsistent effects, with some studies recommending it and others rejecting it. To study the degree to which histology informs on the underlying cause of death, we sent autopsy reports from suspension-, immersion-, fire-, and traffic-related deaths to senior board-certified forensic pathologists and had them assess the cause of death, first without knowledge of the histological findings and then with knowledge thereof. Fifty cases were identified in each of four subgroups: fire-, immersion-, suspension-, and traffic-related deaths. The autopsy reports were anonymized, and the histological findings and conclusions were removed. Two board-certified forensic pathologists independently reviewed the reports in each subgroup and assessed the manner and underlying cause of death (including their certainty of this assessment on a five-level scale) with and without access to histological findings. The probability of changing the underlying cause of death posthistology was low in all study groups. There was a slight increase in the degree of certainty posthistology in cases where the underlying cause of death was not changed, but only when the antehistology certainty was low. Our results suggest that histology does not meaningfully inform on the underlying cause of death in suspension-, immersion-, fire-, and traffic-related deaths except when antehistology certainty is low.
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| 87. |
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| 88. |
- Hansson, Lars-Anders, et al.
(författare)
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A lake as a microcosm : Reflections on developments in aquatic ecology
- 2013
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Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 47, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we aim at relating Forbes' remarkable paper on "The lake as a microcosm", published 125 years ago, to the present status of knowledge in our own research group. Hence, we relate the observations Forbes made to our own microcosm, Lake Krankesjon in southern Sweden, that has been intensively studied by several research groups for more than three decades. Specifically, we focus on the question: Have we made any significant progress or did Forbes and colleagues blaze the trail through the unknown wilderness and we are mainly paving that intellectual road? We conclude that lakes are more isolated than many other biomes, but have, indeed, many extensions, for example, input from the catchment, fishing and fish migration. We also conclude that irrespective of whether lakes should be viewed as microcosms or not, the paper by Forbes has been exceptionally influential and still is, especially since it touches upon almost all aspects of the lake ecosystem, from individual behaviour to food web interactions and environmental issues. Therefore, there is no doubt that even if 125 years have passed, Forbes' paper still is a source of inspiration and deserves to be read. Hence, although aquatic ecology has made considerable progress over the latest century, Forbes might be viewed as one of the major pioneers and visionary scientists of limnology.
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| 89. |
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| 90. |
- Hansson, Lars-Anders, et al.
(författare)
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Consumption patterns, complexity and enrichment in aquatic food chains
- 1998
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 265:1399, s. 901-906
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Tidskriftsartikel (refereegranskat)abstract
- The interactions between consumers and prey, and their impact on biomass distribution among trophic levels, are central issues in both empirical and theoretical ecology. In a long-term experiment, where all organisms, including the top predator, were allowed to respond to environmental conditions by reproduction, we tested predictions from `prey-dependent' and `ratio-dependent' models. Prey-dependent models made correct predictions only in the presence of strong interactors in simple food chains, but failed to predict patterns in more complex situations. Processes such as omnivory, consumer excretion, and unsuitable prey-size windows (invulnerable prey) increased the complexity and created patterns resembling ratio-dependent consumption. However, whereas the prey-dependent patterns were created by the mechanisms predicted by the model, ratio-dependent patterns were not, suggesting that they may be right for the wrong reason'. We show here that despite the enormous complexity of ecosystems, it is possible to identify and disentangle mechanisms responsible for observed patterns in community structure, as well as in biomass development of organisms ranging in size from bacteria to fish.
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| 91. |
- Hansson, Lars-Anders, et al.
(författare)
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Food-chain length alters community responses to global change in aquatic systems
- 2013
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 3, s. 228-233
-
Tidskriftsartikel (refereegranskat)abstract
- Synergies between large-scale environmental changes, such as climate change1 and increased humic content (brownification)2, will have a considerable impact on future aquatic ecosystems. On the basis of modelling, monitoring and experimental data, we demonstrate that community responses to global change are determined by food-chain length and that the top trophic level, and every second level below, will benefit from climate change, whereas the levels in between will suffer. Hence, phytoplankton, and thereby algal blooms, will benefit from climate change in three-, but not in two-trophic-level systems. Moreover, we show that both phytoplankton (resource) and zooplankton (consumer) advance their spring peak abundances similarly in response to a 3 °C temperature increase; that is, there is no support for a consumer/resource mismatch in a future climate scenario. However, in contrast to other taxa, cyanobacteria—known as toxin-producing nuisance phytoplankton3—benefit from a higher temperature and humic content irrespective of the food-chain composition. Our results are mirrored in natural ecosystems. By mechanistically merging present food-chain theory with large-scale environmental and climate changes, we provide a powerful framework for predicting and understanding future aquatic ecosystems and their provision of ecosystem services and water resources.
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| 92. |
- Hansson, Lars-Anders, et al.
(författare)
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Food-chain length alters community responses to global change in aquatic systems
- 2013
-
Ingår i: Nature Climate Change. - 1758-6798. ; 3:3, s. 228-233
-
Tidskriftsartikel (refereegranskat)abstract
- Synergies between large-scale environmental changes, such as climate change(1) and increased humic content (brownification)(2), will have a considerable impact on future aquatic ecosystems. On the basis of modelling, monitoring and experimental data, we demonstrate that community responses to global change are determined by food-chain length and that the top trophic level, and every second level below, will benefit from climate change, whereas the levels in between will suffer. Hence, phytoplankton, and thereby algal blooms, will benefit from climate change in three-, but not in two-trophic-level systems. Moreover, we show that both phytoplankton (resource) and zooplankton (consumer) advance their spring peak abundances similarly in response to a 3 degrees C temperature increase; that is, there is no support for a consumer/resource mismatch in a future climate scenario. However, in contrast to other taxa, cyanobacteria-known as toxin-producing nuisance phytoplankton(3)-benefit from a higher temperature and humic content irrespective of the food-chain composition. Our results are mirrored in natural ecosystems. By mechanistically merging present food-chain theory with large-scale environmental and climate changes, we provide a powerful framework for predicting and understanding future aquatic ecosystems and their provision of ecosystem services and water resources.
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| 93. |
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| 94. |
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| 95. |
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| 96. |
- Hermansson, Ulric, et al.
(författare)
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Screening for high-risk and elevated alcohol consumption in day and shift workers by use of the AUDIT and CDT
- 2003
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Ingår i: Occupational Medicine. - : Oxford University Press (OUP). - 0962-7480 .- 1471-8405. ; 53:8, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- The present findings on employees who attended for regular health examinations suggest that shift workers did not show a higher level of risky alcohol consumption than day workers, according to the results with the AUDIT, CDT and GGT. On the contrary, the two-shift workers appeared to drink significantly less.
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| 97. |
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| 98. |
- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 99. |
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| 100. |
- Iglesias-Gato, Diego, et al.
(författare)
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The Proteome of Primary Prostate Cancer
- 2016
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 69:5, s. 942-952
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries.Objectives: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness.Design, setting, and participants: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker.Results and limitations: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen-and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p < 0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score <= 7 tumors.Conclusions: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors.Patient summary: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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