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"Simona D'Alessio"
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Cross-Cultural Approaches to the Study of “Inclusive” and “Special Needs” Education
Abstract
This chapter explores some of the complexities involved when undertaking research at an international level in the area of “inclusive” education and “special needs” education. The complexities encountered by researchers working in these fields, mirror many of the challenges that comparativists in education studies find themselves addressing. Drawing from earlier investigations and from reports by international organizations, this chapter highlights some of the dilemmas and challenges that researchers face when considering inclusion and special needs education in different countries. Differing interpretations of “inclusion” are discussed and then contrasted with thinking around “special needs” practices. The chapter moves forward to analyze how the adoption of differing theoretical frameworks can influence the way that “disability” is conceptualized and therefore how inclusive and special needs education are interpreted and then put into practice. The chapter argues that cross-cultural work opens up opportunities for further development and learning in this field. We further argue that such cross-cultural work can become a mechanism to instigate fundamental change in education.
Book Chapter
A critical analysis of the policy of integrazione scolastica from an inclusive education perspective: an ethnographic study of disability, discourse and policy making in two lower secondary schools in italy
This thesis provides a critical analysis of the policy of integrazione scolastica in Italy. This educational policy, implemented since 1977, triggered the process of ‘mainstreaming’ disabled students into regular schools. Although the integrazione scolastica is widely considered as being an ideal policy context for the development of inclusive education, my analysis unpacks the tensions and contradictions that emerge from the formulation and implementation of this policy, and particularly, of the ways the policy is materialised through discourses and practices in schools. Through a discussion and application of the social model of disability, and drawing, amongst others, on the works of Foucault, Gramsci, and of inclusive education theorists, this study investigates the extent to which the policy of integrazione scolastica is an inclusive policy. The ethnographic aspects of my research provide a detailed description of case studies of two lower secondary schools in a small city in the north east of Italy. Interviews, observations and documentary analysis provide vivid accounts of the discourses articulated and the ideological framework around which the notion of disability is constructed. I argue that what was once a progressive policy has been transformed into a powerful discourse of normalisation of disability. The cultural practices which arise from this discourse identify problems, determine explanations and look for solutions which limit the possibilities of pursuing potential actions which would be conducive to inclusion. Although the schools investigated proved to be effective exemplars of integrative schools, yet they could not be identified as inclusive schools. This argument is substantiated through the analysis of systemic barriers and institutionalised assumptions which share continuity with those found in special needs education. The thesis makes a case in support of the need to work according to human rights principles rather than through procedures of categorisation which involve the labelling of some students as ‘special’ in order to ‘include’ them.
Dissertation
Researching Disability in Inclusive Education
In this chapter I consider how the adoption of new theoretical perspectives in researching education can impact upon the development of inclusive education research and the dissemination and impact of research findings.
Book Chapter
Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death
The VCP ATPase has been linked to cancer, but the lack of well-defined, selective inhibitors has limited further investigation. A million-molecule screen now identifies a covalent inhibitor as well as an allosteric inhibitor that may freeze the enzyme in an ADP-bound conformation.
VCP (also known as p97 or Cdc48p in yeast) is an AAA
+
ATPase regulating endoplasmic reticulum–associated degradation. After high-throughput screening, we developed compounds that inhibit VCP via different mechanisms, including covalent modification of an active site cysteine and a new allosteric mechanism. Using photoaffinity labeling, structural analysis and mutagenesis, we mapped the binding site of allosteric inhibitors to a region spanning the D1 and D2 domains of adjacent protomers encompassing elements important for nucleotide-state sensing and ATP hydrolysis. These compounds induced an increased affinity for nucleotides. Interference with nucleotide turnover in individual subunits and distortion of interprotomer communication cooperated to impair VCP enzymatic activity. Chemical expansion of this allosteric class identified NMS-873, the most potent and specific VCP inhibitor described to date, which activated the unfolded protein response, interfered with autophagy and induced cancer cell death. The consistent pattern of cancer cell killing by covalent and allosteric inhibitors provided critical validation of VCP as a cancer target.
Journal Article
New variants and genotype–phenotype correlation in KIF5A mutation: the contribution of a large Italian cohort
BackgroundVariants in the Kinesin-family member 5A (KIF5A) gene are associated with a range of motor diseases, and a strong correlation between the protein domains (motor, stalk and tail) and the clinical phenotype has been proposed. However, several studies have reported exceptions contributing to a complex genotype–phenotype correlation in recent years. Further studies are needed to improve our knowledge about the prevalence of KIF5A variants and their genotype–phenotype correlation.Methods390 patients (220 hereditary spastic paraplegia, 80 Charcot-Marie-Tooth disease type 2 and 90 amyotrophic lateral sclerosis) have been selected for next-generation sequencing Clinical Exome.ResultsFive patients have been found to carry causative variants in the KIF5A gene. Of these, three are familiar cases, and two are sporadic. Segregation analysis was performed on the familiar probands. The five patients with pathogenic variants represent 4% of the studied population, and the clinical and genetic analysis of these five families allowed us to examine different scenarios.Some of these data support the hypothesis of a complex correlation between domains and disease.ConclusionThese data confirm the complex genotype–phenotype correlation, both in terms of clinical heterogeneity associated with a specific domain and variability within the members of the same family, but also suggest a strong genotype–phenotype correlation, both intrafamiliar and interfamiliar, produced by a few variants.
Journal Article
Targeting Cathepsins in Neurodegeneration: Biochemical Advances
: Cathepsins, lysosomal proteases crucial for neuronal proteostasis, mediate the clearance of misfolded and aggregated proteins. Their dysregulation is implicated in neurodegenerative and neuropsychiatric disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. These conditions are characterized by toxic protein accumulation and impaired clearance, which exacerbate cellular stress responses, including the unfolded protein response (UPR), oxidative damage, and mitochondrial dysfunction. This review aims to summarize current knowledge on cathepsin roles in these pathways and assess their therapeutic potential.
: A comprehensive literature review was conducted, focusing on recent in vitro and in vivo studies investigating cathepsin function, inhibition, and modulation. Mechanistic insights and pharmacological approaches targeting cathepsins were analyzed, with attention to challenges in translating preclinical findings to clinical settings.
: Cathepsins demonstrate a dual role: their proteolytic activity supports neuronal health by degrading toxic aggregates, but altered or insufficient activity may worsen proteotoxic stress. Studies reveal that cathepsins regulate autophagy, apoptosis, and neuroinflammation both intracellularly and extracellularly. Despite promising mechanistic data, clinical translation is hindered by issues such as poor inhibitor selectivity, limited brain penetration, and variability across preclinical models.
: Targeting cathepsins presents a promising strategy for treating neurodegenerative and neuropsychiatric disorders, but significant challenges remain. Future research should focus on improving drug specificity and delivery, and on developing standardized models to better predict clinical outcomes.
Journal Article
Neuro-Mechanics of Recumbent Leg Cycling in Post-Acute Stroke Patients
Cycling training is strongly applied in post-stroke rehabilitation, but how its modular control is altered soon after stroke has been not analyzed yet. EMG signals from 9 leg muscles and pedal forces were measured bilaterally during recumbent pedaling in 16 post-acute stroke patients and 12 age-matched healthy controls. Patients were asked to walk over a GaitRite mat and standard gait parameters were computed. Four muscle synergies were extracted through nonnegative matrix factorization in healthy subjects and patients unaffected legs. Two to four synergies were identified in the affected sides and the number of synergies significantly correlated with the Motricity Index (Spearman’s coefficient = 0.521). The reduced coordination complexity resulted in a reduced biomechanical performance, with the two-module sub-group showing the lowest work production and mechanical effectiveness in the affected side. These patients also exhibited locomotor impairments (reduced gait speed, asymmetrical stance time, prolonged double support time). Significant correlations were found between cycling-based metrics and gait parameters, suggesting that neuro-mechanical quantities of pedaling can inform on walking dysfunctions. Our findings support the use of pedaling as a rehabilitation method and an assessment tool after stroke, mainly in the early phase, when patients can be unable to perform a safe and active gait training.
Journal Article
Neutralizing IFNγ improves safety without compromising efficacy of CAR-T cell therapy in B-cell malignancies
Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity and macrophage activation syndrome, and the lack of pathophysiological experimental models limit the applicability and development of this form of therapy. Here we present a comprehensive humanized mouse model, by which we show that IFNγ neutralization by the clinically approved monoclonal antibody, emapalumab, mitigates severe toxicity related to CAR-T cell therapy. We demonstrate that emapalumab reduces the pro-inflammatory environment in the model, thus allowing control of severe CRS and preventing brain damage, characterized by multifocal hemorrhages. Importantly, our in vitro and in vivo experiments show that IFNγ inhibition does not affect the ability of CD19-targeting CAR-T (CAR.CD19-T) cells to eradicate CD19+ lymphoma cells. Thus, our study provides evidence that anti-IFNγ treatment might reduce immune related adverse effect without compromising therapeutic success and provides rationale for an emapalumab-CAR.CD19-T cell combination therapy in humans.
B cell malignancies resistant to conventional treatments are potentially sensitive to CAR-T cell immune therapy, but its clinical applicability is limited by immune related adverse effects. Here authors show in a humanized mouse model that blocking IFNγ with the monoclonal antibody emapalumab mitigates the adverse effects of CAR.CD19-T cells without compromising their anti-lymphoma efficacy.
Journal Article