456 research outputs found
Identifying the most appropriate classifier for underpinning assistive technology adoption for people with dementia: an integration of Fuzzy AHP and VIKOR methods
Recently, the number of People with Dementia (PwD) has been rising exponentially across the world. The main symptoms that PwD experience include AQ1 impairments of reasoning, memory, and thought. Owing to the burden faced by this chronic condition, Assistive Technology-based solutions (ATS) have been prescribed as a form of treatment. Nevertheless, it is widely acknowledged that low adoption rates of ATS have hampered their benefits within a health and social care context. It is then necessary to effectively discriminate between adopters and non-adopters of such solutions to avoid cost implications, improve the life quality of adopters, and find intervention alternatives for non-adopters. Several classifiers have been proposed as advancement towards the personalisation of self-management interventions for dementia in a scalable way. As multiple algorithms have been developed, an important step in technology adoption is to select the most appropriate classification alternative based on different criteria. This paper presents the integration of Fuzzy AHP (FAHP) and VIKOR to address this challenge. First, FAHP was used to calculate the criteria and sub-criteria weights under uncertainty and then VIKOR was implemented to rank the classifiers. A case study considering a mobile-based self-management and reminding solution for PwD is described to validate the proposed approach. The results revealed that Easiness of interpretation (GW = 0.192) and Handling of missing data (GW = 0.145) were the two most important criteria. Furthermore, SVM (Qj = 1.0) and AB (Qj = 0.891) were concluded to be the most suitable classifiers for supporting ATS adoption in PwD
Application of the ANP to the prioritization of project stakeholders in the context of responsible research and innovation
[EN] This paper presents a methodology to assess the stakeholdersÂż influence in a research project within the context of responsible research and innovation. The methodology is based on a combination of the multicriteria decision making technique analytic network process and the key areas of responsible research. The method allows ranking and ordering the projectÂżs stakeholders based on their influence upon its responsibility. The purpose of such an assessment is to help research teams to more efficiently devote their limited resources to stakeholder management. The procedure is applied to a case study of the Information and Communication Technology business sector. It is an ongoing project at an early phase of development. Influential stakeholders have been identified first, and have been further classified into groups based on their relative importance. The assessment of their influence has been based on up to 16 different criteria, mainly belonging to the framework of responsible research and innovation. In the case study, the most influential criterion was the Capability to promote public engagement, while Developers were found to be the stakeholders most contributing to the research project responsibility. However, as explained, this is a temporary situation, valid for the current project development situation. It may vary over time as criteria vary in weight and stakeholders vary in influence.The authors would like to thank to our anonymous referees for their constructive comments and suggestions that helped us to improve the quality of the paper. Also, to the “BolĂvar Gana con Ciencia” program from the GobernaciĂłn de BolĂvar (Colombia) for the financial support. For the same reason, the authors are grateful to the Spanish Agencia Estatal de InvestigaciĂłn for its support of the project Propuesta de Indicadores para Impulsar el Diseño de Una PolĂtica Orientada al Desarrollo de InvestigaciĂłn e InnovaciĂłn Responsable en España (CSO2016-76828-R)Ligardo-Herrera, I.; GĂłmez-Navarro, T.; Gonzalez-Urango, H. (2018). Application of the ANP to the prioritization of project stakeholders in the context of responsible research and innovation. Central European Journal of Operations Research. 1-23. https://doi.org/10.1007/s10100-018-0573-4S123Akbari N, Irawan CA, Jones DF, Menachof D (2017) A multi-criteria port suitability assessment for developments in the offshore wind industry. Renew Energy 102:118–133. https://doi.org/10.1016/j.renene.2016.10.035AragonĂ©s-Beltrán P, GarcĂa-MelĂłn M, Montesinos-Valera J (2017) How to assess stakeholders’ influence in project management? A proposal based on the analytic network process. 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Weak and Variable Effects of Exogenous Testosterone on Cognitive Reflection Test Performance in Three Experiments: Commentary on Nave, Nadler, Zava, and Camerer (2017)
Molecular Evolution of the Primate Antiviral Restriction Factor Tetherin
Background: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu). It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the redqueen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. Methodology/Principal Findings: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implyin
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An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Tumor-derived extracellular vesicles (TEV) “educate” healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of downregulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy
Coupling and uncoupling mechanisms in the methoxythreonine mutant of cytochrome P450cam: a quantum mechanical/molecular mechanical study
The Thr252 residue plays a vital role in the catalytic cycle of cytochrome P450cam during the formation of the active species (Compound I) from its precursor (Compound 0). We investigate the effect of replacing Thr252 by methoxythreonine (MeO-Thr) on this protonation reaction (coupling) and on the competing formation of the ferric resting state and H2O2 (uncoupling) by combined quantum mechanical/molecular mechanical (QM/MM) methods. For each reaction, two possible mechanisms are studied, and for each of these the residues Asp251 and Glu366 are considered as proton sources. The computed QM/MM barriers indicate that uncoupling is unfavorable in the case of the Thr252MeO-Thr mutant, whereas there are two energetically feasible proton transfer pathways for coupling. The corresponding rate-limiting barriers for the formation of Compound I are higher in the mutant than in the wild-type enzyme. These findings are consistent with the experimental observations that the Thr252MeO-Thr mutant forms the alcohol product exclusively (via Compound I), but at lower reaction rates compared with the wild-type enzyme
Developing community-driven quality improvement initiatives to enhance chronic disease care in Indigenous communities in Canada : the FORGE AHEAD program protocol
BACKGROUND: Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed. METHODS: The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013-2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations. DISCUSSION: The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to significantly affect future policy decisions pertaining to chronic disease care in First Nations communities in Canada. TRIAL REGISTRATION: Current ClinicalTrial.gov protocol ID NCT02234973 . Date of Registration: July 30, 2014
A contrast between DEMATEL-ANP and ANP methods for six sigma project selection: a case study in healthcare industry
The “Far-West” of Anopheles gambiae Molecular Forms
The main Afrotropical malaria vector, Anopheles gambiae sensu stricto, is undergoing a process of sympatric ecological diversification leading to at least two incipient species (the M and S molecular forms) showing heterogeneous levels of divergence across the genome. The physically unlinked centromeric regions on all three chromosomes of these closely related taxa contain fixed nucleotide differences which have been found in nearly complete linkage disequilibrium in geographic areas of no or low M-S hybridization. Assays diagnostic for SNP and structural differences between M and S forms in the three centromeric regions were applied in samples from the western extreme of their range of sympatry, the only area where high frequencies of putative M/S hybrids have been reported. The results reveal a level of admixture not observed in the rest of the range. In particular, we found: i) heterozygous genotypes at each marker, although at frequencies lower than expected under panmixia; ii) virtually all possible genotypic combinations between markers on different chromosomes, although genetic association was nevertheless detected; iii) discordant M and S genotypes at two X-linked markers near the centromere, suggestive of introgression and inter-locus recombination. These results could be indicative either of a secondary contact zone between M and S, or of the maintenance of ancestral polymorphisms. This issue and the perspectives opened by these results in the study of the M and S incipient speciation process are discussed
Global Retinoblastoma Treatment Outcomes Association with National Income Level
Purpose: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. Design: International, multicenter, registry-based retrospective case series. Participants: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. Methods: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. Main Outcome Measures: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). Results: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). Conclusions: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage. (C) 2020 by the American Academy of Ophthalmology.Peer reviewe
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