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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 4. |
- Hagell, Peter, et al.
(författare)
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Effects of method of translation of patient-reported health outcome questionnaires : a randomized study of the translation of the Rheumatoid Arthritis Quality of Life (RAQoL) Instrument for Sweden
- 2010
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Ingår i: Value in Health. - : Wiley-Blackwell. - 1098-3015 .- 1524-4733. ; 13:4, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare two versions of a questionnaire translated using forward-backward (FB) translation and dual-panel (DP) methodologies regarding preference of wording and psychometric properties.METHODS: The Rheumatoid Arthritis Quality of Life instrument was adapted into Swedish by two independent groups using FB and DP methodologies, respectively. Seven out of thirty resulting items were identical. Nonidentical items were evaluated regarding preference of wording by 23 bilingual Swedes, 50 people with rheumatoid arthritis (RA), and 2 lay panels (n = 11). Psychometric performance was assessed from a postal survey of 200 people with RA randomly assigned to complete one version first and the other 2 weeks later.RESULTS: Preference did not differ among the 23 bilinguals (P = 0.196), whereas patients and lay people preferred DP over FB item versions (P < 0.0001). Postal survey response rates were 74% (FB) and 75% (DP). There were more missing item responses in the FB than the DP version (6.9% vs. 5.6%; P < 0.0001). Floor/ceiling effects were small (FB, 6.1/0%; DP, 4.4/0.7%) and reliability was 0.92 for both versions. Construct validity was similar for both versions. Differential item functioning by version was detected for five items but cancelled out and did not affect estimated person measures.CONCLUSIONS: The DP approach showed advantages over FB translation in terms of preference by the target population and by lay people, whereas there were no obvious psychometric differences. This suggests advantages of DP over FB translation from the patients' perspective, and does not support the commonly held view that FB translation is the "gold standard."
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| 5. |
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| 6. |
- Doward, Lynda C., et al.
(författare)
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International Development of the Unidimensional Fatigue Impact Scale (U-FIS)
- 2010
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015. ; 13:4, s. 463-468
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The 22-item Unidimensional Fatigue Impact Scale (U-FIS) provides an index of the impact of fatigue on patients with multiple sclerosis (MS). The objective is to produce eight new language versions of the U-FIS: Canadian-English, Canadian-French, French, German, Italian, Spanish, Swedish, and US-English. Methods: The U-FIS was translated via two translation panels. Cognitive debriefing interviews conducted with patients in each country assessed face and content validity. Scaling and psychometric properties were assessed via survey data with patients in each country completing the U-FIS, Nottingham Health Profile (NHP), and demographic questions. Results: Cognitive debriefing interviews demonstrated U-FIS acceptability. Analysis of postal survey data showed all new language versions to be unidimensional. Reliability was high, with test-retest correlations and internal-consistency coefficients exceeding 0.85. Initial evidence of validity was provided by moderate to high correlations with NHP scales. The U-FIS was able to discriminate between groups based on employment status, perceived MS severity, and general health. Conclusion: The U-FIS is a practical new measure of the impact of fatigue. It was successfully adapted into eight new languages to broaden availability for researchers. Psychometric analyses indicated that the new language versions were unidimensional and reproducible with promising construct validity.
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| 7. |
- Hagell, Peter, et al.
(författare)
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Effects of Method of Translation of Patient-Reported Health Outcome Questionnaires: A Randomized Study of the Translation of the Rheumatoid Arthritis Quality of Life (RAQoL) Instrument for Sweden.
- 2010
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015. ; 13, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Aims: To compare two versions of a questionnaire translated using forward-backward (FB) translation and dual-panel (DP) methodologies regarding preference of wording and psychometric properties. Methods: The Rheumatoid Arthritis Quality of Life instrument was adapted into Swedish by two independent groups using FB and DP methodologies, respectively. Seven out of thirty resulting items were identical. Nonidentical items were evaluated regarding preference of wording by 23 bilingual Swedes, 50 people with rheumatoid arthritis (RA), and 2 lay panels (n = 11). Psychometric performance was assessed from a postal survey of 200 people with RA randomly assigned to complete one version first and the other 2 weeks later. Results: Preference did not differ among the 23 bilinguals (P = 0.196), whereas patients and lay people preferred DP over FB item versions (P < 0.0001). Postal survey response rates were 74% (FB) and 75% (DP). There were more missing item responses in the FB than the DP version (6.9% vs. 5.6%; P < 0.0001). Floor/ceiling effects were small (FB, 6.1/0%; DP, 4.4/0.7%) and reliability was 0.92 for both versions. Construct validity was similar for both versions. Differential item functioning by version was detected for five items but cancelled out and did not affect estimated person measures. Conclusions: The DP approach showed advantages over FB translation in terms of preference by the target population and by lay people, whereas there were no obvious psychometric differences. This suggests advantages of DP over FB translation from the patients' perspective, and does not support the commonly held view that FB translation is the "gold standard."
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| 8. |
- Hagell, Peter, et al.
(författare)
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Health status measurement in Parkinson's disease : validity of the PDQ-39 and Nottingham Health Profile
- 2003
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Ingår i: Movement Disorders. - : John Wiley & Sons Inc.. - 0885-3185 .- 1531-8257. ; 18:7, s. 773-783
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.
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| 9. |
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| 10. |
- Hagell, Peter, et al.
(författare)
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International use of health status questionnaires in Parkinson's disease: translation is not enough.
- 2003
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 10:2, s. 89-92
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Tidskriftsartikel (refereegranskat)abstract
- The present study assessed the linguistic and content validity of the Swedish version of the 39-item Parkinson's disease questionnaire (PDQ-39). The frame question, response alternatives and two of the 39 items yielded substantial linguistic and stylistic problems. Such shortcomings would be expected to influence responses to, and the quality of, the whole questionnaire. Data support content validity of the PDQ-39 as a functional health status questionnaire, although some shortcomings were identified. This preliminary study illustrates the need for documented linguistic validity before new language adaptations of patient-reported outcome measures can be considered suitable for use in clinical trials, research, and practice.
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