| 1. |
- Berglund, Ann-Charlotte, et al.
(författare)
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Combining local and grid resources in scientific workflows (for Bioinformatics)
- 2009
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Konferensbidrag (refereegranskat)abstract
- We examine some issues that arise when using both local and Gridresources in scientific workflows. Our previous work addresses and illustratesthe benefits of a light-weight and generic workflow engine that manages andoptimizes Grid resource usage. Extending on this effort, we hereillustrate how a client tool for bioinformatics applications employs the engine tointerface with Grid resources. We also explore how to define data flowsthat transparently integrates local and Grid subworkflows. In addition, the benefits of parameter sweep workflows are examined and a means for describing this type of workflows in an abstract and concise manner is introduced. Finally, the above mechanisms are employed to perform an orthology detection analysis.
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| 2. |
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| 3. |
- Karsten, Stella, et al.
(författare)
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MTH1 as a target to alleviate T cell driven diseases by selective suppression of activated T cells
- 2021
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Ingår i: Cell Death & Differentiation. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1350-9047 .- 1476-5403.
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Tidskriftsartikel (refereegranskat)abstract
- T cell-driven diseases account for considerable morbidity and disability globally and there is an urgent need for new targeted therapies. Both cancer cells and activated T cells have an altered redox balance, and up-regulate the DNA repair protein MTH1 that sanitizes the oxidized nucleotide pool to avoid DNA damage and cell death. Herein we suggest that the up-regulation of MTH1 in activated T cells correlates with their redox status, but occurs before the ROS levels increase, challenging the established conception of MTH1 increasing as a direct response to an increased ROS status. We also propose a heterogeneity in MTH1 levels among activated T cells, where a smaller subset of activated T cells does not upregulate MTH1 despite activation and proliferation. The study suggests that the vast majority of activated T cells have high MTH1 levels and are sensitive to the MTH1 inhibitor TH1579 (Karonudib) via induction of DNA damage and cell cycle arrest. TH1579 further drives the surviving cells to the MTH1[superscript low] phenotype with altered redox status. TH1579 does not affect resting T cells, as opposed to the established immunosuppressor Azathioprine, and no sensitivity among other major immune cell types regarding their function can be observed. Finally, we demonstrate a therapeutic effect in a murine model of experimental autoimmune encephalomyelitis. In conclusion, we show proof of concept of the existence of MTH1[superscript high] and MTH1[superscript low] activated T cells, and that MTH1 inhibition by TH1579 selectively suppresses pro-inflammatory activated T cells. Thus, MTH1 inhibition by TH1579 may serve as a novel treatment option against autoreactive T cells in autoimmune diseases, such as multiple sclerosis.
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| 4. |
- Sandman, Lars, et al.
(författare)
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Etik inom ambulanssjukvården
- 2009
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Ingår i: Prehospital akutsjukvård. - : Stockholm: Liber. - 9789147084487 ; , s. 167-179
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Sandman, Lars, et al.
(författare)
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Exploring ethical rationales
- 2017
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Ingår i: Patient invovlement in Health Technology Assessment. - Singapore : Springer Nature. - 9789811040672 - 9789811040689 ; , s. 17-29
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter presents and analyses six ethical rationales for patient involvement in HTA. We have identified three instrumental and three substantive rationales, namely, (1) relevance to healthcare goals and healthcare needs, (2) legitimacy leading to adherence to decisions, (3) capacity building via patient empowerment, (4) fairness and legitimacy through democratic participation, (5) fairness through respect for autonomy and (6) equity. Our ethical analysis finds that these rationales support patient involvement in HTA under specific premises. For example, relevance to healthcare goals and needs mainly support the use of patient-based evidence, while the other rationales require patient participation in some form. That is, for HTA to be legitimate enough to increase adherence, patients probably need to participate in the process and the same goes for equity. Likewise, when the rationales are democratic participation, empowerment and autonomy. Importantly, in order to achieve strong ethical support for patient involvement in HTA, it is crucial to ensure that these premises and their preconditions are fulfilled. On the other hand, all rationales raise issues of representation, i.e. which patient group should be represented through evidence or participation.
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| 6. |
- Scott, Anna Mae, et al.
(författare)
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Q-SEA – a tool for quality assessment of ethics analyses conducted as part of health technology assessments
- 2017
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Ingår i: GMS Health Technology Assessment. - 1861-8863. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Assessment of ethics issues is an important part of health technology assessments (HTA). However, in terms of existence of quality assessment tools, ethics for HTA is methodologically under-developed in comparison to other areas of HTA, such as clinical or cost effectiveness.Objective: To methodologically advance ethics for HTA by: (1) proposing and elaborating Q-SEA, the first instrument for quality assessment of ethics analyses, and (2) applying Q-SEA to a sample systematic review of ethics for HTA, in order to illustrate and facilitate its use. Methods: To develop a list of items for the Q-SEA instrument, we sys-tematically reviewed the literature on methodology in ethics for HTA, reviewed HTA organizations’ websites, and solicited views from 32 ex-perts in the field of ethics for HTA at two 2-day workshops. We sub-sequently refined Q-SEA through its application to an ethics analysis conducted for HTA.Results: Q-SEA instrument consists of two domains – the process do-main and the output domain. The process domain consists of 5 ele-ments: research question, literature search, inclusion/exclusion criteria, perspective, and ethics framework. The output domain consists of 5 elements: completeness, bias, implications, conceptual clarification, and conflicting values.Conclusion: Q-SEA is the first instrument for quality assessment of ethics analyses in HTA. Further refinements to the instrument to enhance its usability continue.
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| 7. |
- Scott, Anna Mae, et al.
(författare)
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QUALITY ASSESSMENT OF ETHICS ANALYSES FOR HEALTH TECHNOLOGY ASSSESSMENT
- 2016
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Ingår i: International Journal of Technology Assessment in Health Care. - New York : Cambridge University Press. - 0266-4623 .- 1471-6348. ; 32:5, s. 362-369
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Although consideration of ethical issues is recognized as a crucial part of health technology assessment, ethics analysis for HTA is generally perceived as methodologically underdeveloped in comparison to other HTA domains. The aim of our study is (i) to verify existing tools for quality assessment of ethics analyses for HTA, (ii) to consider some arguments for and against the need for quality assessment tools for ethics analyses for HTA, and (iii) to propose a preliminary set of criteria that could be used for assessing the quality of ethics analyses for HTA.Methods: We systematically reviewed the literature, reviewed HTA organizations’ Web sites, and solicited views from thirty-two experts in the field of ethics for HTA.Results: The database and HTA agency Web site searches yielded 420 references (413 from databases, seven from HTA Web sites). No formal instruments for assessing the quality of ethics analyses for HTA purposes were identified. Thirty-two experts in the field of ethics for HTA from ten countries, who were brought together at two workshops held in Edmonton (Canada) and Cologne (Germany) confirmed the findings from the literature.Conclusions: Generating a quality assessment tool for ethics analyses in HTA would confer considerable benefits, including methodological alignment with other areas of HTA, increase in transparency and transferability of ethics analyses, and provision of common language between the various participants in the HTA process. We propose key characteristics of quality assessment tools for this purpose, which can be applied to ethics analyses for HTA purposes.
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