The Clinical Outcome Study for dysferlinopathy: An international multicenter study

Objective: To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy. Methods: The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments. Results: There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies. Conclusions: These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design

Assessment of disease progression in dysferlinopathy: A 1-year cohort study

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077

Assessment of disease progression in dysferlinopathy: A 1-year cohort study

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077

Hong Kong puzzle films:the persistence of tradition

This chapter examines the fate of traditional modes of practice, as well as of local storytelling norms, in contemporary Hong Kong cinema. It contests some widely-held yet arguably specious assumptions: first, that the "Mainlandization" and "Hollywoodization" of Hong Kong cinema eradicate local filmmaking practices and aesthetic norms; and second, that the local routine of piecemeal script construction yields slapdash plotting, and thus is inferior to the screenplay practices advocated in Mainland China and Hollywood. This chapter argues that not only have local work routines endured in spite of institutional change, but that those practices yield films of considerable complexity and ambition. The chapter's major case studies - Wu Xia (2011), Mad Detective (2007), and Blind Detective (2013) - can be assimilated to a nascent puzzle film trend in Hong Kong cinema. Disputing claims of a "post-Hong Kong cinema," this chapter draws on primary interviews with Hong Kong filmmakers in detailing both the PRC coproduction system and the characteristic script practices employed by Peter Chan, Johnnie To, and the Milkyway Image film studio

Data from: Assessment of disease progression in dysferlinopathy – a one year cohort study

Objective: To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. Methods: 193 patients with dysferlinopathy were recruited to the Jain Foundation’s International Clinical Outcome Study for Dysferlinopathy. Baseline, 6 months and 1 year assessments included: adapted North Star Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6 minute walk test (6MWT), Brooke Scale, Jebsen Test, manual muscle testing (MMT) and hand-held dynamometry (HHD). Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant (mild, moderate or severe based on a-NSAA score) or non-ambulant (unable to complete a 10m walk)) and clinical diagnosis. Results: The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate group while 6MWT was most sensitive in the severe group. The 10m walk test was the only test showing significant change across all ambulant severity groups. In non-ambulant patients, the MFM domain 3, wrist flexion strength and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1 year clinical trial based on the a-NSAA as a clinical endpoint. Conclusion: Certain functional outcome measures can detect changes over 6 months and one year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials

Evaluating Criminalisation as a Strategy in Relation to Non-Physical Family Violence

This chapter reflects broadly on the use of criminalisation as a strategy for addressing the harms and risks related to non-physical family violence. It aims to contribute to constructive dialogue over whether we should adopt new forms of criminalisation to combat non-physical family violence and, if so, how we should criminalise. This chapter is organised around three lines of inquiry. First, a consideration of whether a different \u27logic\u27 of criminalisation operates in relation to domestic violence when compared to other subject matter or \u27sites\u27 of criminal lawmaking. Secondly, a discussion about the care that needs to be taken when \u27borrowing\u27 criminalisation innovations to address coercive non-physical forms of domestic violence from other policy settings and jurisdictions. Finally, an examination of how we should approach the detection of a \u27gap\u27 in existing legal arrangements and the considerations that should inform what statutory architecture is appropriate for filling any gap so identified

Assessment of disease progression in dysferlinopathy. A 1-year cohort study

Jain COS Consortium.[Objective] To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.[Methods] One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.[Results] The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.[Conclusion] Certain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.[ClinicalTrials.gov identifier] NCT01676077.The estimated US $4 million needed to fund this study is being provided by the Jain Foundation. The John Walton Centre Muscular Dystrophy Research Centre is part of the MRC Centre for Neuromuscular Diseases (grant MR/K000608/1)