Individual Vulnerability and Cultural Transformation

Perhaps the most pressing problem in multicultural theory and practice today is the problem of individual vulnerability. Most interested theorists and multicultural states now accept the basic premise that some degree of state accommodation of minority cultural practice is required as a matter of justice. Debate then shifts to the best justifications for, and the appropriate extent of, such groupdifferentiated policy. Too often lost amid these discussions is the plight of vulnerable members of accommodated cultural groups: individuals subject to repression within their cultural groups, but who lose a critical aspect of their identities upon exit; individuals who would retain their cultural membership, but also their rights as individuals. It is not that the problem of individual cultural vulnerability goes unsolved because it goes unnoticed. Rather, the problem itself receives little prescriptive attention because most theorists who consider the problem consider it to be insoluble. In her valuable new book on multiculturalism, however, Ayelet Shachar takes the plight of vulnerable cultural group members, particularly women, as her primary focus. Further, she offers innovative legal-institutional prescriptions designed to permit the retention and simultaneous transformation of cultural identities. Yet, in Multicultural Jurisdictions, Shachar also underestimates the extent to which her legal model is derivative of extant theory and overestimates the efficacy of her own prescriptive design

A Better Characterization of Spinal Cord Damage in Multiple Sclerosis: A Diffusional Kurtosis Imaging Study

BACKGROUND AND PURPOSE: The spinal cord is a site of predilection for MS lesions. While diffusion tensor imaging is useful for the study of anisotropic systems such as WM tracts, it is of more limited utility in tissues with more isotropic microstructures (on the length scales studied with diffusion MR imaging) such as gray matter. In contrast, diffusional kurtosis imaging, which measures both Gaussian and non-Gaussian properties of water diffusion, provides more biomarkers of both anisotropic and isotropic structural changes. The aim of this study was to investigate the cervical spinal cord of patients with MS and to characterize lesional and normal-appearing gray matter and WM damage by using diffusional kurtosis imaging. MATERIALS AND METHODS: Nineteen patients (13 women, mean age = 41.1 ± 10.7 years) and 16 controls (7 women, mean age = 35.6 ± 11.2-years) underwent MR imaging of the cervical spinal cord on a 3T scanner (T2 TSE, T1 magnetization-prepared rapid acquisition of gradient echo, diffusional kurtosis imaging, T2 fast low-angle shot). Fractional anisotropy, mean diffusivity, and mean kurtosis were measured on the whole cord and in normal-appearing gray matter and WM. RESULTS: Spinal cord T2-hyperintense lesions were identified in 18 patients. Whole spinal cord fractional anisotropy and mean kurtosis ( P = .0009, P = .003), WM fractional anisotropy ( P = .01), and gray matter mean kurtosis ( P = .006) were significantly decreased, and whole spinal cord mean diffusivity ( P = .009) was increased in patients compared with controls. Mean spinal cord area was significantly lower in patients ( P = .04). CONCLUSIONS: Diffusional kurtosis imaging of the spinal cord can provide a more comprehensive characterization of lesions and normal-appearing WM and gray matter damage in patients with MS. Diffusional kurtosis imaging can provide additional and complementary information to DTI on spinal cord pathology

INCIDENCE OF HIGH GRADE QTCF PROLONGATION AND ITS MANAGEMENT AMONG PATIENTS UNDERGOING TREATMENT FOR DRUG RESISTANT TUBERCULOSIS (DR-TB): CASE SERIES.

Background: The World Health Organization (WHO) has approved the use of two new drugs, namely Bedaquiline (Bdq) and Delamanid (Dlm), for treatment of Drug Resistant Tuberculosis (DR-TB). One of the concerns raised with the use of these drugs was QT-interval prolongation. This condition could be serious and life threatening. Hence, knowing the magnitude and its management is very important. This case series identifies the incidence and discusses the management of clinically significant QT-interval prolongation amongst a cohort of patients who have been on these medicines. Materials and Methods: Patients with reports of high grade QT-Interval prolongation (i.e. Grade-3 and Grade-4) were identified from the cohort of 265 patients enrolled on bedaquiline and/delamanid and discussion is made on the pattern, severity and management of each cases identified. Results: Only 4 (1.5%) out of all 265 patients enrolled on Bedaquiline and/or Delamanid have developed high grade QT-Interval prolongation. And all are managed without permanent discontinuation of both drugs. Conclusion: The Incidence of clinically significant QTcF-interval prolongation among DR-TB patients taking bedaquiline and delamanid in Lesotho is low. And almost all cases can be managed with more frequent Electrocardiogram (ECG) monitoring and management of other possible causes of QT-interval prolongation without the need to stop one or both drugs permanentl

Scaling Up Programmatic Management of Drug-Resistant Tuberculosis: A Prioritized Research Agenda

Frank Cobelens and colleagues outline key research questions that need to be addressed to maximize the impact of programmatic management of drug-resistant tuberculosis

Issues in design and interpretation of MDR-TB clinical trials: report of the first Global MDR-TB Clinical Trials Landscape Meeting

Recognizing that the current MDR-TB regimen is suboptimal and based on low-quality evidence, the Global MDR-TB Clinical Trials Landscape Meeting was held in December, 2014 to strategize about coordination of research and development of new treatment regimens for this disease that affects millions of people worldwide every year. Sixty international experts on multidrug-resistant tuberculosis (MDR-TB) met in Washington D.C. and Cape Town, South Africa to consider key MDR-TB trial-related issues, including: standardization of definitions; clinical trial capacity building and; regimens optimized to foster compliance, avoid the emergence of resistance and have clinical relevance for special populations, including children and those co-infected with HIV. Underpinning all of this is the generation of a sufficient evidence base to facilitate regulatory approval and improved normative guidance. Participants discussed treatment combinations currently being studied in Phase 2B and Phase 3 trials as well as other promising new regimens and combinations that may be evaluated in the near future. These include regimens designed specifically to enable shorter duration and all-oral treatment as a means of maximizing treatment completion. It is hoped that clear definition of these challenges will facilitate the process of identifying solutions that accelerate progress towards effective, non-toxic treatments that can be programmatically implemented

Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008

Running head: Targeted Drug-Resistance Testing Strategy for MDR T

Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs

What is regulation? An interdisciplinary concept analysis

The concept of regulation is believed to suffer from a lack of shared understanding. Yet, the maturation of the field raises the question whether this conclusion is still valid. By taking a new methodological approach towards this question of conceptual consolidation, this study assesses how regulation is conceived in the most-cited articles in six social science disciplines. Four main conclusions are drawn. First, there is a remarkable absence of explicit definitions. Second, the scope of the concept is vast, which requires us to talk about regulation in rather abstract terms. Third, scholars largely agree that ‘prototype regulation’ is characterised by interventions which are intentional and direct – involving binding standard-setting, monitoring and sanctioning – and exercised by public-sector actors on the economic activities of private-sector actors. Fourth, while there is considerable variation in research concerns, this variation cannot be attributed to disciplinary differences. Instead, our findings support the portrayal of the field as interdisciplinary, including a shared conception of regulation