| 1. |
- Aad, G., et al.
(författare)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Tidskriftsartikel (refereegranskat)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 2. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 9. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 10. |
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| 11. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 12. |
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| 13. |
- O'Connor, C. M., et al.
(författare)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 14. |
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| 15. |
- Flodin, P, et al.
(författare)
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Differential impact of the COVID-19 pandemic on primary care utilization related to common mental disorders in four European countries: A retrospective observational study
- 2023
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13, s. 1045325-
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic is commonly believed to have increased common mental disorders (CMD, i.e., depression and anxiety), either directly due to COVID-19 contractions (death of near ones or residual conditions), or indirectly by increasing stress, economic uncertainty, and disruptions in daily life resulting from containment measure. Whereas studies reporting on initial changes in self-reported data frequently have reported increases in CMD, pandemic related changes in CMD related to primary care utilization are less well known. Analyzing time series of routinely and continuously sampled primary healthcare data from Sweden, Norway, Netherlands, and Latvia, we aimed to characterize the impact of the pandemic on CMD recorded prevalence in primary care. Furthermore, by relating these changes to country specific time-trajectories of two classes of containment measures, we evaluated the differential impact of containment strategies on CMD rates. Specifically, we wanted to test whether school restrictions would preferentially affect age groups corresponding to those of school children or their parents.MethodsFor the four investigated countries, we collected time-series of monthly counts of unique CMD patients in primary healthcare from the year 2015 (or 2017) until 2021. Using pre-pandemic timepoints to train seasonal Auto Regressive Integrated Moving Average (ARIMA) models, we predicted healthcare utilization during the pandemic. Discrepancies between observed and expected time series were quantified to infer pandemic related changes. To evaluate the effects of COVID-19 measures on CMD related primary care utilization, the predicted time series were related to country specific time series of levels of social distancing and school restrictions.ResultsIn all countries except Latvia there was an initial (April 2020) decrease in CMD care prevalence, where largest drops were found in Sweden (Prevalence Ratio, PR = 0.85; 95% CI 0.81–0.90), followed by Netherlands (0.86; 95% CI 0.76–1.02) and Norway (0.90; 95% CI 0.83–0.98). Latvia on the other hand experienced increased rates (1.25; 95% CI 1.08–1.49). Whereas PRs in Norway and Netherlands normalized during the latter half of 2020, PRs stayed low in Sweden and elevated in Latvia. The overall changes in PR during the pandemic year 2020 was significantly changed only for Sweden (0.91; 95% CI 0.90–0.93) and Latvia (1.20; 95% CI 1.14–1.26). Overall, the relationship between containment measures and CMD care prevalence were weak and non-significant. In particular, we could not observe any relationship of school restriction to CMD care prevalence for the age groups best corresponding to school children or their parents.ConclusionCommon mental disorders prevalence in primary care decreased during the initial phase of the COVID-19 pandemic in all countries except from Latvia, but normalized in Norway and Netherlands by the latter half of 2020. The onset of the pandemic and the containment strategies were highly correlated within each country, limiting strong conclusions on whether restriction policy had any effects on mental health. Specifically, we found no evidence of associations between school restrictions and CMD care prevalence. Overall, current results lend no support to the common belief that the pandemic severely impacted the mental health of the general population as indicated by healthcare utilization, apart from in Latvia. However, since healthcare utilization is affected by multiple factors in addition to actual need, future studies should combine complementary types of data to better understand the mental health impacts of the pandemic.
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| 16. |
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| 17. |
- Paul, D.J., et al.
(författare)
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n-type Si/SiGe resonant tunnelling diodes
- 2002
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Ingår i: Materials Science & Engineering. - 0921-5107 .- 1873-4944. ; 89:1-3, s. 26-29
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Resonant tunnelling diodes (RTDs) have been fabricated using Si/SiGe heterolayers which demonstrate room temperature performance comparable to III-V technology. Peak current densities up to 282 kA cm-2 with peak-to-valley current ratios (PVCRs) of 2.4 have been demonstrated at room temperature in devices with dimensions of 5 × 5 µm2. Scaling the device size demonstrates that the peak current density is inversely proportional to the device area. It is suggested that this is related to thermal limitations in the device structure. Estimates are also produced for the maximum frequency of oscillations of the diodes which suggest that oscillators may operate with speeds comparable to III-V diodes. © 2002 Elsevier Science B.V. All rights reserved.
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| 18. |
- Paul, D.J., et al.
(författare)
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Si/SiGe electron resonant tunneling diodes with graded spacer wells
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 78:26, s. 4184-4186
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Tidskriftsartikel (refereegranskat)abstract
- Resonant tunneling diodes have been fabricated using graded Si1 - xGex (x = 0.3?0.0) spacer wells and strained Si0.4Ge0.6 barriers on a relaxed Si0.7Ge0.3 n-type substrate which demonstrates negative differential resistance at up to 100 K. This design is aimed at reducing the voltage at which the peak current density is achieved. Peak current densities of 0.08 A/cm2 with peak-to-valley current ratios of 1.67 have been achieved for a low peak voltage of 40 mV at 77 K. This represents an improvement of over an order of magnitude compared to previous work. © 2001 American Institute of Physics.
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| 19. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 20. |
- Aktaa, Suleman, et al.
(författare)
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European Society of Cardiology Quality Indicators for Cardiovascular Disease Prevention: developed by the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with the European Association for Preventive Cardiology of the European Society of Cardiology
- 2022
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Ingår i: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881. ; 23:7, s. 1060-1071
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Tidskriftsartikel (refereegranskat)abstract
- Aims To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention. Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes. Conclusion We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.
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| 21. |
- Apple, FS, et al.
(författare)
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IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 201-203
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Tidskriftsartikel (refereegranskat)abstract
- In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described.
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| 22. |
- Bourdeau, P. E., et al.
(författare)
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What can aquatic gastropods tell us about phenotypic plasticity? A review and meta-analysis
- 2015
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 115:4, s. 312-321
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Tidskriftsartikel (refereegranskat)abstract
- There have been few attempts to synthesise the growing body of literature on phenotypic plasticity to reveal patterns and generalities about the extent and magnitude of plastic responses. Here, we conduct a review and meta-analysis of published literature on phenotypic plasticity in aquatic (marine and freshwater) gastropods, a common system for studying plasticity. We identified 96 studies, using pre-determined search terms, published between 1985 and November 2013. The literature was dominated by studies of predator-induced shell form, snail growth rates and life history parameters of a few model taxa, accounting for 67% of all studies reviewed. Meta-analyses indicated average plastic responses in shell thickness, shell shape, and growth and fecundity of freshwater species was at least three times larger than in marine species. Within marine gastropods, species with planktonic development had similar average plastic responses to species with benthic development. We discuss these findings in the context of the role of costs and limits of phenotypic plasticity and environmental heterogeneity as important constraints on the evolution of plasticity. We also consider potential publication biases and discuss areas for future research, indicating well-studied areas and important knowledge gaps.
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| 23. |
- Chen, J. Y., et al.
(författare)
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High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGERB and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps.
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| 24. |
- Conde-Padin, P., et al.
(författare)
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Revealing the mechanisms of sexual isolation in a case of sympatric and parallel ecological divergence
- 2008
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Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 94:3, s. 513-526
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Tidskriftsartikel (refereegranskat)abstract
- Two ecotypes of a marine intertidal snail (Littorina saxatilis), living at different microhabitats and shore levels, have evolved in sympatry and in parallel across the Galician rocky shore. These ecotypes differ in many traits (including size) due to differential adaptation. They meet, mate assortatively, and partially hybridize at the mid shore where the two microhabitats overlap. The partial sexual isolation observed is claimed to be a side-effect of the size differences between ecotypes combined with a size assortative mating found in most populations of this species. We investigated this hypothesis using three complementary experimental approaches. First, we investigated which of the different shell variables contributed most to the variation in individual sexual isolation in the field by using two new statistics developed for that purpose: (1) pair sexual isolation and (2) r(i), which is based on the Pearson correlation coefficient. We found that size is the most important trait explaining the sexual isolation and, in particular, the males appear to be the key sex contributing to sexual isolation. Second, we compared the size assortative mating between regions: exposed rocky shore populations from north-westwern Spain (showing incomplete reproductive isolation due to size assortative mating) and protected Spanish and Swedish populations (showing size assortative mating but not reproductive isolation between ecomorphs). Most of the variation in size assortative mating between localities was significantly explained by the within-population level of variation on size. Third, we performed a laboratory male choice experiment, which further suggested that the choice is made predominantly on the basis of size. These results confirm the mechanism proposed to explain the sexual isolation in the Galician hybrid zone and thus support this case as a putative example of parallel incipient speciation. (C) 2008 The Linnean Society of London.
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| 25. |
- de Hollander, Ellen L., et al.
(författare)
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The association between waist circumference and risk of mortality considering body mass index in 65-to 74-year-olds : a meta-analysis of 29 cohorts involving more than 58 000 elderly persons
- 2012
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 41:3, s. 805-817
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Tidskriftsartikel (refereegranskat)abstract
- Background For the elderly, the association between waist circumference (WC) and mortality considering body mass index (BMI) remains unclear, and thereby also the evidence base for using these anthropometric measures in clinical practice. This meta-analysis examined the association between WC categories and (cause-specific) mortality within BMI categories. Furthermore, the association of continuous WC with lowest and increased mortality risks was examined. Methods Age-and smoking-adjusted relative risks (RRs) of mortality associated with WC-BMI categories and continuous WC (including WC and WC2) were calculated by the investigators and pooled by means of random-effects models. Results During a 5-year-follow-up of 32 678 men and 25 931 women, we ascertained 3318 and 1480 deaths, respectively. A large WC (men: >= 102 cm, women: >= 88 cm) was associated with increased all-cause mortality RRs for those in the 'healthy' weight {1.7 [95% confidence interval (CI): 1.2-2.2], 1.7 (95% CI: 1.3-2.3)}, overweight [1.1(95% CI: 1.0-1.3), 1.4 (95%: 1.1-1.7)] and obese [1.1 (95% CI: 1.0-1.3), 1.6 (95% CI: 1.3-1.9)] BMI category compared with the 'healthy' weight (20-24.9 kg/m(2)) and a small WC (<94 cm, men; <80 cm, women) category. Underweight was associated with highest all-cause mortality RRs in men [2.2 (95% CI: 1.8-2.8)] and women [2.3 (95% CI: 1.8-3.1]. We found a J-shaped association for continuous WC with all-cause, cardiovascular (CVD) and cancer, and a U-shaped association with respiratory disease mortality (P < 0.05). An all-cause (CVD) mortality RR of 2.0 was associated with a WC of 132 cm (123 cm) in men and 116 cm (105 cm) in women. Conclusions Our results showed increased mortality risks for elderly people with an increased WC-even across BMI categories- and for those who were classified as 'underweight' using BMI. The results provide a solid basis for re-evaluation of WC cut-points in ageing populations.
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| 26. |
- de Jong, Sarah, et al.
(författare)
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Effect of rare coding variants in the CFI gene on Factor I expression levels
- 2020
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:14, s. 2313-2324
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Tidskriftsartikel (refereegranskat)abstract
- Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level analysis of rare coding variants in CFI to date. More than half of CFI variants lead to reduced FI expression, which might impair complement regulation in vivo. Our study will aid the interpretation of rare coding CFI variants identified in clinical practice, which is in particular important in light of patient inclusion in ongoing clinical trials for CFI gene supplementation in AMD.
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| 27. |
- de Jong, Sarah, et al.
(författare)
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Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Complement factor I (FI) is a central inhibitor of the complement system, and impaired FI function increases complement activation, contributing to diseases such as age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS). Genetic variation in complement factor I (CFI) has been identified in both AMD and aHUS, with more than half of these variants leading to reduced FI secretion levels. For many of the variants with normal FI secretion, however, functional implications are not yet known. Here we studied 11 rare missense variants, with FI secretion levels comparable to wildtype, but a predicted damaging effects based on the Combined Annotation Dependent Depletion (CADD) score. Three variants (p.Pro50Ala, p.Arg339Gln, and p.Ser570Thr) were analyzed in plasma and serum samples of carriers affected by AMD. All 11 variants (nine for the first time in this study) were recombinantly expressed and the ability to degrade C3b was studied with the C3b degradation assay. The amount of degradation was determined by measuring the degradation product iC3b with ELISA. Eight of 11 (73%) mutant proteins (p.Pro50Ala, p.Arg339Gln, p.Ile340Thr, p.Gly342Glu, p.Gly349Arg, p.Arg474Gln, p.Gly487Cys, and p.Gly512Ser) showed significantly impaired C3b degradation, and were therefore classified as likely pathogenic. Our data indicate that genetic variants in CFI with a CADD score >20 are likely to affect FI function, and that monitoring iC3b in a degradation assay is a useful tool to establish the pathogenicity of CFI variants in functional studies.
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| 28. |
- de Waard, Anne-Karien M., et al.
(författare)
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Selective prevention of cardiometabolic diseases : activities and attitudes of general practitioners across Europe
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 29:1, s. 88-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiometabolic diseases (CMDs) are the number one cause of death. Selective prevention of CMDs by general practitioners (GPs) could help reduce the burden of CMDs. This measure would entail the identification of individuals at high risk of CMDsubut currently asymptomaticufollowed by interventions to reduce their risk. No data were available on the attitude and the extent to which European GPs have incorporated selective CMD prevention into daily practice.Methods: A survey among 575 GPs from the Czech Republic, Denmark, Greece, the Netherlands and Sweden was conducted between September 2016 and January 2017, within the framework of the SPIMEU-project.Results: On average, 71% of GPs invited their patients to attend for CMD risk assessment. Some used an active approach (47%) while others used an opportunistic approach (53%), but these values differed between countries. Most GPs considered selective CMD prevention as useful (82%) and saw it as part of their normal duties (84%). GPs who did find selective prevention useful were more likely to actively invite individuals compared with their counterparts who did not find prevention useful. Most GPs had a disease management programme for individuals with risk factor(s) for cardiovascular disease (71%) or diabetes (86%).Conclusions: Although most GPs considered selective CMD prevention as useful, it was not universally implemented. The biggest challenge was the process of inviting individuals for risk assessment. It is important to tailor the implementation of selective CMD prevention in primary care to the national context, involving stakeholders at different levels.
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| 29. |
- den Hollander, F., et al.
(författare)
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Bad configurations for random walk in random scenery and related subshifts
- 2005
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Ingår i: Stochastic Processes and their Applications. - : Elsevier BV. - 0304-4149. ; 115:7, s. 1209-1232
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we consider an arbitrary irreducible random walk on ℤd, d ≥ 1, with i.i.d. increments, together with an arbitrary i.i.d. random scenery. Walk and scenery are assumed to be independent. Random walk in random scenery (RWRS) is the random process where time is indexed by ℤ, and at each unit of time both the step taken by the walk and the scenery value at the site that is visited are registered. Bad configurations for RWRS are the discontinuity points of the conditional probability distribution for the configuration at the origin of time given the configuration at all other times. We show that the set of bad configurations is non-empty. We give a complete description of this set and compute its probability under the random scenery measure. Depending on the type of random walk, this probability may be zero or positive. For simple symmetric random walk we get three different types of behavior depending on whether d = 1, 2, d = 3, 4 or d ≥ 5. Our classification is actually valid for a class of subshifts having a certain determinative property, which we call specifiable, of which RWRS is an example. We also consider bad configurations w.r.t. a finite time interval (replacing the origin) and obtain an almost complete generalization of our results. Remarkably, this extension turns out to be somewhat delicate.
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| 30. |
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| 31. |
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| 32. |
- Gururaj, AE, et al.
(författare)
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MTA1, a transcriptional activator of breast cancer amplified sequence 3
- 2006
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:17, s. 6670-6675
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Tidskriftsartikel (refereegranskat)abstract
- Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Iveson, Timothy J., et al.
(författare)
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3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT) : an international, randomised, phase 3, non-inferiority trial
- 2018
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 19:4, s. 562-578
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Tidskriftsartikel (refereegranskat)abstract
- Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1: 1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1.13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76.7% (95% CI 75.1-78.2) for the 3 month group and 77.1% (75.6-78.6) for the 6 month group, giving a hazard ratio of 1.006 (0.909-1.114, test for non-inferiority p=0.012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
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| 38. |
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| 39. |
- Lionis, C, et al.
(författare)
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High Variability in Implementation of Selective-Prevention Services for Cardiometabolic Diseases in Five European Primary Care Settings
- 2020
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:23
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Cardiometabolic diseases are the most common cause of death worldwide. As part of a collaborative European study, this paper aims to explore the implementation of primary care selective-prevention services in five European countries. We assessed the implementation process of the selective-prevention services, participants’ cardiometabolic profile and risk and participants’ evaluation of the services, in terms of feasibility and impact in promoting a healthy lifestyle. (2) Methods: Eligible participants were primary care patients, 40–65 years of age, without any diagnosis of cardiometabolic disease. Two hundred patients were invited to participate per country. The extent to which participants adopted and completed the implementation of selective-prevention services was recorded. Patient demographics, lifestyle-related cardiometabolic risk factors and opinions on the implementation’s feasibility were also collected. (3) Results: Acceptance rates varied from 19.5% (n = 39/200) in Sweden to 100% (n = 200/200) in the Czech Republic. Risk assessment completion rates ranged from 65.4% (n = 70/107) in Greece to 100% (n = 39/39) in Sweden. On a ten-point scale, the median (25–75% quartile) of participant-reported implementation feasibility ranged from 7.4 (6.9–7.8) in Greece to 9.2 (8.2–9.9) in Sweden. Willingness to change lifestyle exceeded 80% in all countries. (4) Conclusions: A substantial variation in the implementation of selective-prevention receptiveness and patient risk profile was observed among countries. Our findings suggest that the design and implementation of behavior change cardiometabolic programmes in each country should be informed by the local context and provide some background evidence towards this direction, which can be even more relevant during the current pandemic period.
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| 40. |
- Littink, Karin W., et al.
(författare)
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Homozygosity Mapping in Patients with Cone-Rod Dystrophy : Novel Mutations and Clinical Characterizations
- 2010
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:11, s. 5943-5951
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone-rod dystrophy (CRD) patients. METHODS. One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination. RESULTS. Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging. CONCLUSIONS. Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2.
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| 41. |
- Mackay, Donna S, et al.
(författare)
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Screening of a Large Cohort of Leber Congenital Amaurosis and Retinitis Pigmentosa Patients Identifies Novel LCA5 Mutations and New Genotype-Phenotype Correlations
- 2013
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 34:11, s. 1537-1546
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Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to investigate the prevalence of sequence variants in LCA5 in patients with Leber congenital amaurosis (LCA), early-onset retinal dystrophy (EORD), and autosomal recessive retinitis pigmentosa (arRP); to delineate the ocular phenotypes; and to provide an overview of all published LCA5 variants in an online database. Patients underwent standard ophthalmic evaluations after providing informed consent. In selected patients, optical coherence tomography (OCT) and fundus autofluorescence imaging were possible. DNA samples from 797 unrelated patients with LCA and 211 with the various types of retinitis pigmentosa (RP) were screened by Sanger sequence analysis of all LCA5 exons and intron/exon junctions. Some LCA patients were prescreened by APEX technology or selected based on homozygosity mapping. In silico analyses were performed to assess the pathogenicity of the variants. Segregation analysis was performed where possible. Published and novel LCA5 variants were collected, amended for their correct nomenclature, and listed in a Leiden Open Variation Database (LOVD). Sequence analysis identified 18 new probands with 19 different LCA5 variants. Seventeen of the 19 LCA5 variants were novel. Except for two missense variants and one splice site variant, all variants were protein-truncating mutations. Most patients expressed a severe phenotype, typical of LCA. However, some LCA subjects had better vision and intact inner segment/outer segment (IS/OS) junctions on OCT imaging. In two families with LCA5 variants, the phenotype was more compatible with EORD with affected individuals displaying preserved islands of retinal pigment epithelium. One of the families with a milder phenotype harbored a homozygous splice site mutation; a second family was found to have a combination of a stop mutation and a missense mutation. This is the largest LCA5 study to date. We sequenced 1,008 patients (797 with LCA, 211 with arRP) and identified 18 probands with LCA5 mutations. Mutations in LCA5 are a rare cause of childhood retinal dystrophy accounting for ∼2% of disease in this cohort, and the majority of LCA5 mutations are likely null. The LCA5 protein truncating mutations are predominantly associated with LCA. However, in two families with the milder EORD, the LCA5 gene analysis revealed a homozygous splice site mutation in one and a stop mutation in combination with a missense mutation in a second family, suggesting that this milder phenotype is due to residual function of lebercilin and expanding the currently known phenotypic spectrum to include the milder early onset RP. Some patients have remaining foveal cone structures (intact IS/OS junctions on OCT imaging) and remaining visual acuities, which may bode well for upcoming treatment trials.
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| 42. |
- Mai, P., et al.
(författare)
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Towards functionally individualised designed footwear recommendation for overuse injury prevention : a scoping review
- 2023
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Ingår i: BMC Sports Science, Medicine and Rehabilitation. - : Springer Nature. - 2052-1847. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- Injury prevention is essential in running due to the risk of overuse injury development. Tailoring running shoes to individual needs may be a promising strategy to reduce this risk. Novel manufacturing processes allow the production of individualised running shoes that incorporate features that meet individual biomechanical and experiential needs. However, specific ways to individualise footwear to reduce injury risk are poorly understood. Therefore, this scoping review provides an overview of (1) footwear design features that have the potential for individualisation; and (2) the literature on the differential responses to footwear design features between selected groups of individuals. These purposes focus exclusively on reducing the risk of overuse injuries. We included studies in the English language on adults that analysed: (1) potential interaction effects between footwear design features and subgroups of runners or covariates (e.g., age, sex) for running-related biomechanical risk factors or injury incidences; (2) footwear comfort perception for a systematically modified footwear design feature. Most of the included articles (n = 107) analysed male runners. Female runners may be more susceptible to footwear-induced changes and overuse injury development; future research should target more heterogonous sampling. Several footwear design features (e.g., midsole characteristics, upper, outsole profile) show potential for individualisation. However, the literature addressing individualised footwear solutions and the potential to reduce biomechanical risk factors is limited. Future studies should leverage more extensive data collections considering relevant covariates and subgroups while systematically modifying isolated footwear design features to inform footwear individualisation.
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| 43. |
- Marques, João P., et al.
(författare)
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Transcriptomic resources for evolutionary studies in flat periwinkles and related species
- 2020
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- © 2020, The Author(s). The flat periwinkles, Littorina fabalis and L. obtusata, comprise two sister gastropod species that have an enormous potential to elucidate the mechanisms involved in ecological speciation in the marine realm. However, the molecular resources currently available for these species are still scarce. In order to circumvent this limitation, we used RNA-seq data to characterize the transcriptome of four individuals from each species sampled in different locations across the Iberian Peninsula. Four de novo transcriptome assemblies were generated, as well as a pseudo-reference using the L. saxatilis reference transcriptome as backbone. After transcripts’ annotation, variant calling resulted in the identification of 19,072 to 45,340 putatively species-diagnostic SNPs. The discriminatory power of a subset of these SNPs was validated by implementing an independent genotyping assay to characterize reference populations, resulting in an accurate classification of individuals into each species and in the identification of hybrids between the two. These data comprise valuable genomic resources for a wide range of evolutionary and conservation studies in flat periwinkles and related taxa.
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| 44. |
- Meghini, C., et al.
(författare)
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ARIADNE: A Research Infrastructure for Archaeology
- 2017
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Ingår i: ACM Journal on Computing and Cultural Heritage. - : Association for Computing Machinery (ACM). - 1556-4673 .- 1556-4711. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Research e-infrastructures, digital archives, and data services have become important pillars of scientific enterprise that in recent decades have become ever more collaborative, distributed, and data intensive. The archaeological research community has been an early adopter of digital tools for data acquisition, organization, analysis, and presentation of research results of individual projects. However, the provision of e-infrastructure and services for data sharing, discovery, access, and (re) use have lagged behind. This situation is being addressed by ARIADNE, the Advanced Research Infrastructure for Archaeological Dataset Networking in Europe. This EU-funded network has developed an e-infrastructure that enables data providers to register and provide access to their resources (datasets, collections) through the ARIADNE data portal, facilitating discovery, access, and other services across the integrated resources. This article describes the current landscape of data repositories and services for archaeologists in Europe, and the issues that make interoperability between them difficult to realize. The results of the ARIADNE surveys on users' expectations and requirements are also presented. The main section of the article describes the architecture of the e-infrastructure, core services (data registration, discovery, and access), and various other extant or experimental services. The ongoing evaluation of the data integration and services is also discussed. Finally, the article summarizes lessons learned and outlines the prospects for the wider engagement of the archaeological research community in the sharing of data through ARIADNE.
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| 45. |
- Osika, W, et al.
(författare)
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Early findings from periscope (Pan-European response to the impacts of COVID-19 and future pandemics and epidemics)
- 2021
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Ingår i: EUROPEAN PSYCHIATRY. - : Royal College of Psychiatrists. - 0924-9338 .- 1778-3585. ; 64, s. S34-S34
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The H2020/PERISCOPE project, including 32 partners from European universities & agencies, began 1st November 2020 and will last 36 months. The overarching objectives of PERISCOPE are to map and analyse the unintended impacts of the COVID-19 outbreak; develop solutions and guidance for policymakers and health authorities on how to mitigate the impact of the outbreak; enhance Europe’s preparedness for future similar events; and reflect on the future multi-level governance in the health as well as other domains affected by the outbreak. During this session we will report about early lessons learnt from the mapping and assessments of the impacts of the COVID-19 outbreak on mental health at national and subnational level in the EU with respect to individuals, communities and societies. Further, we will comment on their comparability. The aim is to explore differences between countries regarding the occurrence of mental ill health, and especially the impact on vulnerable groups, and how this is related to exposure to SARS-CoV-2, differences in policies over time, and effects on the economy. We will reflect on the short- and long-term consequences on mental health and health inequalities, report on the ongoing development of holistic policy guidelines for health authorities & other authorities, and from the analysis of multilevel governance, at local, regional and national level, memberstate – EU-level, and EU - global governance level. PERISCOPE will continue collecting data and updating a common data ”Atlas”, which would lead the consortium to engage in modelling and experiments to provide “continuous nowcasting” of the outbreak.DisclosureNo significant relationships.
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| 46. |
- Paul, DJ, et al.
(författare)
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Si/SiGe electron resonant tunneling diodes
- 2000
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Ingår i: Applied Physics Letters. - 0003-6951 .- 1077-3118. ; 77:11, s. 1653-1655
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Tidskriftsartikel (refereegranskat)abstract
- Resonant tunneling diodes have been fabricated using strained-Si wells and strained Si0.4Ge0.6 barriers on a relaxed Si0.8Ge0.2 n-type substrate, which demonstrate negative differential resistance at 298 K. Peak current densities of 5 kA/cm(2) with peak-to-valley current ratios of 1.1 have been achieved. Theoretical modeling of the structure demonstrates that the major current peak results from the tunneling of light-mass electrons from the relaxed substrate and not from the heavy-mass electrons in the emitter accumulation layer. (C) 2000 American Institute of Physics. [S0003- 6951(00)02337-8].
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| 47. |
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| 48. |
- Robles-Zurita, Jose, et al.
(författare)
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SCOT : a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer
- 2018
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:11, s. 1332-1338
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTS: The 3M arm is less costly (-4881; pound 95% CI: -6269; pound -3492) pound and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3M had lower QALYs than 6M (not statistically significant).CONCLUSIONS: Overall, 3M dominates 6M with no significant detrimental impact on QALYs. The results provide the economic case that a 3M treatment strategy should be considered a new standard of care.
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| 49. |
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| 50. |
- See, P., et al.
(författare)
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High performance Si/Si1-x Gex resonant tunneling diodes
- 2001
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Ingår i: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 22:4, s. 182-184
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Tidskriftsartikel (refereegranskat)abstract
- Resonant tunneling diodes (RTDs) with strained i-Si0.4 Ge06. potential barriers and a strained i-Si quantum well, all on a relaxed Si0.8 Ge0.2 virtual substrate were successfully grown by ultra high vacuum compatible chemical vapor deposition and fabricated using standard Si processing methods. A large peak to valley current ratio of 2.9 and a peak current density of 4.3 kA/cm2 at room temperature were recorded from pulsed and continuous dc current-voltage measurements, the highest reported values to date for Si/Si1-x Gex RTDs. These dc figures of merit and material system render such structures suitable and highly compatible with present high speed and low power Si/Si1-x Gex heterojunction field effect transistor based integrated circuits.
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