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| 2. |
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 12. |
- Pfaller, M.A., et al.
(författare)
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Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
- 2004
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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| 14. |
- Adamczewski-Musch, J., et al.
(författare)
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Production and electromagnetic decay of hyperons : a feasibility study with HADES as a phase-0 experiment at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- A feasibility study has been performed in order to investigate the performance of the HADES detector to measure the electromagnetic decays of the hyperon resonances Sigma(1385)(0), Lambda(1405) and Lambda(1520) as well as the production of double strange baryon systems Xi(-) and Lambda Lambda in p + p reactions at a beam kinetic energy of 4.5GeV. The existing HADES detector will be upgraded by a new Forward Detector, which extends the detector acceptance into a range of polar angles that plays a crucial role for these investigations. The analysis of each channel is preceded by a consideration of the production cross-sections. Afterwards the expected signal count rates using a target consisting of either liquid hydrogen or polyethylene are summarized.
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| 15. |
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| 16. |
- Kalman, L. V., et al.
(författare)
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Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
- 2016
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
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Tidskriftsartikel (refereegranskat)abstract
- This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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| 17. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 18. |
- Ng, M Y M, et al.
(författare)
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Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
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Tidskriftsartikel (refereegranskat)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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| 19. |
- Uusitupa, M., et al.
(författare)
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Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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| 20. |
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| 21. |
- Aguilar, J., et al.
(författare)
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Search for Leptonic CP Violation with the ESSnuSBplus Project
- 2024
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Ingår i: Letters in High Energy Physics. - : Andromeda Publishing And Academic Services LTD. - 2632-2714.
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Tidskriftsartikel (refereegranskat)abstract
- ESSνSB is a design study for a next-generation long-baseline neutrino experiment that aims at the precise measurement of the CP-violating phase, δCP, in the leptonic sector at the second oscillation maximum. The conceptual design report published from the first phase of the project showed that after 10 years of data taking, more than 70% of the possible δCP range will be covered with 5σ C.L. to reject the no-CP-violation hypothesis. The expected value of δCP precision is smaller than 8◦ for all δCP values. The next phase of the project, the ESSνSB+, aims at using the intense muon flux produced together with neutrinos to measure the neutrino-nucleus cross-section, the dominant term of the systematic uncertainty, in the energy range of 0.2–0.6 GeV, using a Low Energy neutrinos from STORed Muons (LEnuSTORM) and a Low Energy Monitored Neutrino Beam (LEMNB) facilities.
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| 22. |
- Aguilar, J., et al.
(författare)
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Study of nonstandard interactions mediated by a scalar field at the ESSnuSB experiment
- 2024
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 109:11
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we study scalar mediator induced nonstandard interactions (SNSIs) in the context of the ESSnuSB experiment. In particular, we study the capability of ESSnuSB to put bounds on the SNSI parameters and also study the impact of SNSIs in the measurement of the leptonic CP phase δCP. Existence of SNSIs modifies the neutrino mass matrix and this modification can be expressed in terms of three diagonal real parameters (ηee, ημμ, and ηττ) and three off-diagonal complex parameters (ηeμ, ηeτ, and ημτ). Our study shows that the upper bounds on the parameters ημμ and ηττ depend upon how Δm312 is minimized in the theory. However, this is not the case when one tries to measure the impact of SNSIs on δCP. Further, we show that the CP sensitivity of ESSnuSB can be completely lost for certain values of ηee and ημτ for which the appearance channel probability becomes independent of δCP.
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| 23. |
- Dragsted, L., et al.
(författare)
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Metabolomic response to Nordic foods
- 2015
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Ingår i: Annals of Nutrition and Metabolism. - 0250-6807 .- 1421-9697. ; 67, s. 55-55
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Gau, Rémi, et al.
(författare)
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Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
- 2021
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Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
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Tidskriftsartikel (refereegranskat)abstract
- Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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| 27. |
- Harrison, C. J., et al.
(författare)
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An international study of intrachromosomal amplification of chromosome 21 (iAMP21) : cytogenetic characterization and outcome
- 2014
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 28:5, s. 1015-1021
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Tidskriftsartikel (refereegranskat)abstract
- Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.
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| 28. |
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| 29. |
- Ruuth, M., et al.
(författare)
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Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, ismodifiable, and associates with future cardiovascular deaths
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:27
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Tidskriftsartikel (refereegranskat)abstract
- Aims Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization. Methods and results We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture. Conclusion Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.
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| 30. |
- Schwab, M. B., et al.
(författare)
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Visualization of relativistic laser pulses in underdense plasma
- 2020
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Ingår i: Physical Review Accelerators and Beams. - 2469-9888. ; 23:2
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Tidskriftsartikel (refereegranskat)abstract
- We present experimental evidence of relativistic electron-cyclotron resonances (RECRs) in the vicinity of the relativistically intense pump laser of a laser wakefield accelerator (LWFA). The effects of the RECRs are visualized by imaging the driven plasma wave with a few-cycle, optical probe in transverse geometry. The probe experiences strong, spectrally dependent and relativistically modified birefringence in the vicinity of the pump that arises due to the plasma electrons' relativistic motion in the pump's electromagnetic fields. The spectral birefringence is strongly dependent on the local magnetic field distribution of the pump laser. Analysis and comparison to both 2D and 3D particle-in-cell simulations confirm the origin of the RECR effect and its appearance in experimental and simulated shadowgrams of the laser-plasma interaction. The RECR effect is relevant for any relativistic, magnetized plasma and in the case of LWFA could provide a nondestructive, in situ diagnostic for tracking the evolution of the pump's intensity distribution with propagation through tenuous plasma.
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| 31. |
- Anderson, Christopher D., et al.
(författare)
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Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:3, s. 612-619
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods-This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results-IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). Conclusions-This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. (Stroke. 2013;44:612-619.)
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| 32. |
- Biffi, Alessandro, et al.
(författare)
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APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:8, s. 702-709
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Tidskriftsartikel (refereegranskat)abstract
- Background Carriers of APOE epsilon 2 and epsilon 4 have an increased risk of intracerebral haemorrhage (ICH) in lobar regions, presumably because of the effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed to assess whether these variants also associate with severity of ICH, in terms of haematoma volume at presentation and subsequent outcome. Methods We investigated the association of APOE epsilon 2 and epsilon 4 with ICH volume and outcomes in patients with primary ICH in three phases: a discovery phase of 865 individuals of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation study, and replication phases of 946 Europeans (replication 1) and 214 African-Americans (replication 2) from an additional six studies. We also assessed the association of APOE variants with ICH volume and outcomes in meta-analyses of results from all three phases, and the association of APOE epsilon 4 with mortality in a further meta-analysis including data from previous reports. Admission ICH volume was quantified on CT scan. We assessed functional outcome (modified Rankin scale score 3-6) and mortality at 90 days. We used linear regression to establish the effect of genotype on haematoma volume and logistic regression to assess the effect on outcome from ICH. Findings For patients with lobar ICH, carriers of the APOE epsilon 2 allele had larger ICH volumes than did non-carriers in the discovery phase (p=2. 5x10(-5)), in both replication phases (p=0.008 in Europeans and p=0.016 in African-Americans), and in the meta-analysis (p=3.2x10(-8)). In the meta-analysis, each copy of APOE epsilon 2 increased haematoma size by a mean of 5.3 mL (95% CI 4.7-5.9; p=0.004). Carriers of APOE epsilon 2 had increased mortality (odds ratio [OR] 1.50, 95% CI 1.23-1.82; p=2.45x10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6; 1-52, 1.25-1.85; p=1.74x10(-5)) compared with non-carriers after lobar ICH. APOE epsilon 4 was not associated with lobar ICH volume, functional outcome, or mortality in the discovery phase, replication phases, or meta-analysis of these three phases; in our further meta-analysis of 2194 patients, this variant did not increase risk of mortality (1.08,0.86-1.36; p=0.52). APOE allele variants were not associated with deep ICH volume, functional outcome, or mortality. Interpretation Vasculopathic changes associated with the APOE epsilon 2 allele might have a role in the severity and clinical course of lobar ICH. Screening of patients who have ICH to identify the epsilon 2 variant might allow identification of those at increased risk of mortality and poor functional outcomes.
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| 33. |
- Devan, William J., et al.
(författare)
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Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:6, s. 1578-1583
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE. Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.
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| 34. |
- Falcone, Guido J., et al.
(författare)
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Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
- 2012
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:11, s. 2877-2883
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.)
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| 35. |
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| 36. |
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| 38. |
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| 39. |
- Lankinen, Maria A., et al.
(författare)
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Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome
- 2010
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 20:4, s. 249-57
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue.METHODS AND RESULTS: Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.CONCLUSION: Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.
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| 40. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 41. |
- López-Cano, M., et al.
(författare)
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EHS clinical guidelines on the management of the abdominal wall in the context of the open or burst abdomen
- 2018
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Ingår i: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 22:6, s. 921-939
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers of the abdominal wall, and regarding possible materials to be used. Methods: The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument. Results: For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE. Recommendations: When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.
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| 42. |
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| 43. |
- Picetti, Edoardo, et al.
(författare)
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Early management of adult traumatic spinal cord injury in patients with polytrauma : a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)
- 2024
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Ingår i: World Journal of Emergency Surgery. - : BioMed Central (BMC). - 1749-7922. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak).Conclusions: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.
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| 44. |
- Province, M. A., et al.
(författare)
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CYP2D6 Genotype and Adjuvant Tamoxifen : Meta-Analysis of Heterogeneous Study Populations
- 2014
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Ingår i: Clinical Pharmacology and Therapeutics. - New York, USA : Nature Publishing Group. - 0009-9236 .- 1532-6535. ; 95:2, s. 216-227
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Tidskriftsartikel (refereegranskat)abstract
- The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
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| 45. |
- Ringleb, P, et al.
(författare)
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Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection
- 2019
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. Methods Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). Conclusions Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
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| 46. |
- Roeder, SS, et al.
(författare)
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Evidence for postnatal neurogenesis in the human amygdala
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 366-
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Tidskriftsartikel (refereegranskat)abstract
- The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus.
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| 47. |
- Schwab, G., et al.
(författare)
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Lack of direct association between oral mucosal lesions and SARS-CoV-2 in a cohort of patients hospitalised with COVID-19
- 2022
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Ingår i: Journal of Oral Microbiology. - : Informa UK Limited. - 2000-2297. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background COVID-19 is a disease affecting various human organs and systems, in which the virus seeks to interact with angiotensin-converting enzyme 2 receptors. These receptors are present in the oral cavity, but the direct relationship between such an interaction and possible oral manifestations of COVID-19 is still unclear. Aim The present study evaluated oral manifestations in a cohort of COVID-19 patients during the period of hospitalisation. Methods In total, 154 patients presenting moderate-to-severe forms of COVID-19 had their oral mucosa examined twice a week until the final outcome, either discharge or death. The oral alterations observed in the patients were grouped into Group 1 (pre-existing conditions and opportunistic oral lesions) and Group 2 (oral mucosal changes related to hospitalization). Results Oral lesions found in the patients of Group 1 are not suggestive of SARS-CoV-2 infection as they are mainly caused by opportunistic infections. On the other hand, oral alterations found in the patients of Group 2 were statistically (P < 0.001) related to intubation and longer period of hospitalisation. Conclusion It is unlikely that ulcerative lesions in the oral cavity are a direct manifestation of SARS-CoV-2 or a marker of COVID-19 progression.
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