Facing homelessness

In facing homelessness we face the other, and in facing the other, we face ourselves. This book contributes to an emerging body of knowledge on street homelessness in the South African context. It is meant for researchers and scholars who are committed to finding solutions for street homelessness. It offers conceptual frameworks and practical guidelines for a liberative and transformative response to homelessness. It brings together authors from a wide range of disciplines, fusing the rigour of researchers, the vision of activists and the lived experience of practitioners. In this volume, the causes of street homelessness in South Africa today, and its different faces, are traced. It critiques singular solutions, and interrogates the political, institutional and moral failures that contribute to the systemic exclusion of homeless persons and other vulnerable populations from society. It proposes rights-based interventions as part of a radical re-imagination of how street homelessness can be ended, one person and one neighbourhood at a time. The analysis by the authors steer in the direction of new ways of doing and being that could demonstrate concrete, viable and sustainable alternatives to the exclusionary realities faced by homeless persons. It argues for solution-based approaches, aimed at radical forms of social inclusion and achieved through broad-based and creative collaborations by all spheres of society. In the face and presence of street homelessness – as one expression of urban vulnerability and deep socio-economic inequality – society is confronted with a clear political, institutional, moral and personal obligation. This volume calls for a reclamation of community in its most inclusionary, life-affirming and interdependent sense, asserting that we truly are well because of others, and we are unwell if others are. It is a call to reclaim our common humanity in the context of inclusive communities where all are equally welcome and bestowed with dignity and honour

Facing homelessness

In facing homelessness we face the other, and in facing the other, we face ourselves. This book contributes to an emerging body of knowledge on street homelessness in the South African context. It is meant for researchers and scholars who are committed to finding solutions for street homelessness. It offers conceptual frameworks and practical guidelines for a liberative and transformative response to homelessness. It brings together authors from a wide range of disciplines, fusing the rigour of researchers, the vision of activists and the lived experience of practitioners. In this volume, the causes of street homelessness in South Africa today, and its different faces, are traced. It critiques singular solutions, and interrogates the political, institutional and moral failures that contribute to the systemic exclusion of homeless persons and other vulnerable populations from society. It proposes rights-based interventions as part of a radical re-imagination of how street homelessness can be ended, one person and one neighbourhood at a time. The analysis by the authors steer in the direction of new ways of doing and being that could demonstrate concrete, viable and sustainable alternatives to the exclusionary realities faced by homeless persons. It argues for solution-based approaches, aimed at radical forms of social inclusion and achieved through broad-based and creative collaborations by all spheres of society. In the face and presence of street homelessness – as one expression of urban vulnerability and deep socio-economic inequality – society is confronted with a clear political, institutional, moral and personal obligation. This volume calls for a reclamation of community in its most inclusionary, life-affirming and interdependent sense, asserting that we truly are well because of others, and we are unwell if others are. It is a call to reclaim our common humanity in the context of inclusive communities where all are equally welcome and bestowed with dignity and honour

DNAJC6 Mutations Disrupt Dopamine Homeostasis in Juvenile Parkinsonism‐Dystonia

BACKGROUND: Juvenile forms of parkinsonism are rare conditions with onset of bradykinesia, tremor and rigidity before the age of 21 years. These atypical presentations commonly have a genetic aetiology, highlighting important insights into underlying pathophysiology. Genetic defects may affect key proteins of the endocytic pathway and clathrin-mediated endocytosis (CME), as in DNAJC6-related juvenile parkinsonism. OBJECTIVE: To report on a new patient cohort with juvenile-onset DNAJC6 parkinsonism-dystonia and determine the functional consequences on auxilin and dopamine homeostasis. METHODS: Twenty-five children with juvenile parkinsonism were identified from a research cohort of patients with undiagnosed pediatric movement disorders. Molecular genetic investigations included autozygosity mapping studies and whole-exome sequencing. Patient fibroblasts and CSF were analyzed for auxilin, cyclin G-associated kinase and synaptic proteins. RESULTS: We identified 6 patients harboring previously unreported, homozygous nonsense DNAJC6 mutations. All presented with neurodevelopmental delay in infancy, progressive parkinsonism, and neurological regression in childhood. 123 I-FP-CIT SPECT (DaTScan) was performed in 3 patients and demonstrated reduced or absent tracer uptake in the basal ganglia. CSF neurotransmitter analysis revealed an isolated reduction of homovanillic acid. Auxilin levels were significantly reduced in both patient fibroblasts and CSF. Cyclin G-associated kinase levels in CSF were significantly increased, whereas a number of presynaptic dopaminergic proteins were reduced. CONCLUSIONS: DNAJC6 is an emerging cause of recessive juvenile parkinsonism-dystonia. DNAJC6 encodes the cochaperone protein auxilin, involved in CME of synaptic vesicles. The observed dopamine dyshomeostasis in patients is likely to be multifactorial, secondary to auxilin deficiency and/or neurodegeneration. Increased patient CSF cyclin G-associated kinase, in tandem with reduced auxilin levels, suggests a possible compensatory role of cyclin G-associated kinase, as observed in the auxilin knockout mouse. DNAJC6 parkinsonism-dystonia should be considered as a differential diagnosis for pediatric neurotransmitter disorders associated with low homovanillic acid levels. Future research in elucidating disease pathogenesis will aid the development of better treatments for this pharmacoresistant disorder. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

What does cell therapy manufacturing cost?: A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings

BACKGROUND AIMS: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing framework and methodology for academic and other small-scale facilities that manufacture cell-based therapies. METHODS: We conducted an international multi-center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and technicians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill-finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running (fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros (€). RESULTS: The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between €23 033 and €190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices. CONCLUSIONS: This framework and methodology provide step-by-step guidance to estimate manufacturing costs specifically for cell-based therapies manufactured in academic and other small-scale enterprises. The framework and methodology can be used to inform and plan cost-conscious strategies for CBTs

What does cell therapy manufacturing cost?: A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings

BACKGROUND AIMS: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing framework and methodology for academic and other small-scale facilities that manufacture cell-based therapies. METHODS: We conducted an international multi-center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and technicians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill-finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running (fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros (€). RESULTS: The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between €23 033 and €190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices. CONCLUSIONS: This framework and methodology provide step-by-step guidance to estimate manufacturing costs specifically for cell-based therapies manufactured in academic and other small-scale enterprises. The framework and methodology can be used to inform and plan cost-conscious strategies for CBTs