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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Dondorp, W., et al.
(författare)
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Non-invasive prenatal testing for aneuploidy and beyond : challenges of responsible innovation in prenatal screening
- 2015
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Ingår i: Eur J Hum Genet. - : Springer Science and Business Media LLC. ; 23:11, s. 1438-1450
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Tidskriftsartikel (refereegranskat)abstract
- This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.
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| 6. |
- Radulovic, M., et al.
(författare)
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Another Trip to the Wall: How Much Will Stacked DRAM Benefit HPC?
- 2015
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Ingår i: ACM International Conference Proceeding Series - Proceedings of the 1st International Symposium on Memory Systems, MEMSYS 2015, Washington, United States, 14-15 August 2015. - New York, NY, USA : ACM. - 9781450336048 ; 05-08-October-2015, s. 31-36
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Konferensbidrag (refereegranskat)abstract
- First defined two decades ago, the memory wall remains a fundamental limitation to system performance. Recent innovations in 3D-stacking technology enable DRAM devices with much higher bandwidths than traditional DIMMs. The first such products will soon hit the market, and some of the publicity claims that they will break through the memory wall. Here we summarize our analysis and expectations of how such 3D-stacked DRAMs will affect the memory wall for a set of representative HPC applications. We conclude that although 3D-stacked DRAM is a major technological innovation, it cannot eliminate the memory wall.
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- Castellani, Carlo, et al.
(författare)
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Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
- 2008
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 7:3, s. 179-96
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Tidskriftsartikel (refereegranskat)abstract
- It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.
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| 9. |
- De Wert, G., et al.
(författare)
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Responsible innovation in human germline gene editing : Background document to the recommendations of ESHG and ESHRE
- 2018
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 26:4, s. 450-470
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Tidskriftsartikel (refereegranskat)abstract
- Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, preclinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g., gene editing goes against nature) do not seem convincing while consequentialist objections (e.g., safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.
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| 11. |
- Howard, Heidi Carmen, et al.
(författare)
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One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans
- 2018
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 26:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Gene editing, which allows for specific location(s) in the genome to be targeted and altered by deleting, adding or substituting nucleotides, is currently the subject of important academic and policy discussions. With the advent of efficient tools, such as CRISPR-Cas9, the plausibility of using gene editing safely in humans for either somatic or germ line gene editing is being considered seriously. Beyond safety issues, somatic gene editing in humans does raise ethical, legal and social issues (ELSI), however, it is suggested to be less challenging to existing ethical and legal frameworks; indeed somatic gene editing is already applied in (pre-) clinical trials. In contrast, the notion of altering the germ line or embryo such that alterations could be heritable in humans raises a large number of ELSI; it is currently debated whether it should even be allowed in the context of basic research. Even greater ELSI debates address the potential use of germ line or embryo gene editing for clinical purposes, which, at the moment is not being conducted and is prohibited in several jurisdictions. In the context of these ongoing debates surrounding gene editing, we present herein guidance to further discussion and investigation by highlighting three crucial areas that merit the most attention, time and resources at this stage in the responsible development and use of gene editing technologies: (1) conducting careful scientific research and disseminating results to build a solid evidence base; (2) conducting ethical, legal and social issues research; and (3) conducting meaningful stakeholder engagement, education and dialogue.
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- Pruner, I, et al.
(författare)
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The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor
- 2020
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 66:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C>T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases.MethodsTo determine the frequency of the FII c.1824C>T variant we have sequenced patients’ DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C>T variant. Scanning electron microscopy was used to examine the structure of fibrin clots.ResultsFrequency of the FII c.1824C>T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C>T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis.ConclusionOur data indicate that FII c.1824C>T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C>T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
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| 13. |
- Zivanovic, D., et al.
(författare)
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Main Memory in HPC: Do We Need More or Could We Live with Less?
- 2017
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Ingår i: Transactions on Architecture and Code Optimization. - : Association for Computing Machinery (ACM). - 1544-3973 .- 1544-3566. ; 14:1, s. Article nr 3-
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of High-Performance Computing (HPC) system design is the choice of main memory capacity. This choice becomes increasingly important now that 3D-stacked memories are entering the market. Compared with conventional Dual In-line Memory Modules (DIMMs), 3D memory chiplets provide better performance and energy efficiency but lower memory capacities. Therefore, the adoption of 3D-stacked memories in the HPC domain depends on whether we can find use cases that require much less memory than is available now. This study analyzes the memory capacity requirements of important HPC benchmarks and applications. We find that the High-Performance Conjugate Gradients (HPCG) benchmark could be an important success story for 3D-stacked memories in HPC, but High-Performance Linpack (HPL) is likely to be constrained by 3D memory capacity. The study also emphasizes that the analysis of memory footprints of production HPC applications is complex and that it requires an understanding of application scalability and target category, i. e., whether the users target capability or capacity computing. The results show that most of the HPC applications under study have per-core memory footprints in the range of hundreds of megabytes, but we also detect applications and use cases that require gigabytes per core. Overall, the study identifies the HPC applications and use cases with memory footprints that could be provided by 3D-stacked memory chiplets, making a first step toward adoption of this novel technology in the HPC domain.
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