Reply to Nina Hood\u27s \u27Manifestations of autonomy and control in a devolved schooling system. The case of New Zealand\u27

Hood\u27s contribution in this issue offers a useful problematization of the concept of professional autonomy, its conditions and the challenges it faces when teachers navigate contradictory aspects of the school system. However, this could have been further utilized, in light of the specific characteristics of the New Zealand system, to produce a more fine-grained analysis of how it connects to the issue of accountability and to the explanation of changes in teachers\u27 experiences and practices following the reforms discussed. (DIPF/Orig.

Inequality, poverty and the grounds of our normative concerns

Policy debates surrounding poverty and inequality try to find practical solutions to what we should do to tackle these phenomena. But what are the grounds for being concerned about poverty or about inequality? To what extent do these overlap? These questions invite us to explore the conceptual links between the two notions from the standpoint of their normative justifications. This paper clarifies the normative debate surrounding poverty and inequality, highlighting both moral and non-moral reasons that ground our concerns. The result is a clear map of the key philosophical positions, connected to current empirical debates in social policy. What emerges from this analysis is the possibility of endorsing a broader social justice justification for which poverty and inequality do not generate competing concerns, but see, instead, our normative reasons to care about both overlap

Why we should care about poverty and inequality: exploring the grounds for a pluralist approach

Policy debates surrounding poverty and inequality often focus on practical solutions and seldom explore the normative underpinning that would justify our concerns with these phenomena. Why should we care about poverty, or about inequality? From a philosophical standpoint, can we separate the two, such that it is possible to be deeply concerned about poverty but unconcerned about inequalities? Do our reasons for caring about one contrast with our reasons for caring about the other? While there is a growing empirical literature exploring the mechanisms connecting the two, the philosophical literature has seldom focused on their relationship. Firstly, this paper provides a clear map of the philosophical debate, clarifying the normative assumptions that underlie positions conceptually prioritizing inequality and poverty respectively. Secondly, the paper suggests ‘a pluralist approach’, that stresses the overlap of our normative concerns with poverty and inequality and highlights parallel problems that restrictive interpretations of these concepts face, pointing to the importance of considering broader phenomena and processes (such as deprivation and exclusion) that illuminate the relationship between the two

Design of a randomized, placebo-controlled, Phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers: The ATLAS study

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS

Myopathy with anti-HMGCR antibodies: Perimysium and myofiber pathology

OBJECTIVE: To analyze clinical features and myopathology changes in muscle fibers, connective tissue, and vessels in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody–associated myopathies. METHODS: Retrospective review of records and myopathologic features of 49 consecutive patients with myopathies and serum HMGCR antibodies. RESULTS: Clinical features included onset age from 12 to 83 years, female predominance (67%), proximal, symmetric weakness (84%), muscle discomfort (78%), dysphagia (35%), systemic features, including skin rash and interstitial lung disease (37%), statin use (38%), and a high serum creatine kinase (83%). Myopathology included muscle fiber necrosis or regeneration (66%), myonuclear pathology (43%), perimysial connective tissue damage (61%), and lymphocytic foci (27%). CONCLUSIONS: Patients with HMGCR antibody–associated myopathies present with weakness and muscle discomfort and often have damage to both perimysial connective tissue and muscle fibers, with necrosis and myonuclear pathology. Only a minority of patients with HMGCR antibody–associated myopathies have a history of statin exposure