'A beginning and not the end’: Work after a diagnosis of dementia

YesWhile there is a growing literature on the experiences of disabled workers, this article presents an account of a work experience not frequently documented: being employed while living with dementia. It does this through the account of Elizabeth Draper, an NHS Hospital Trust manager, who received a diagnosis of dementia while employed. The article offers new ways of conceptualizing the struggles of disabled workers to continue with their project of self-becoming through work. It shows how work practices can enact violence through ‘non-recognition’ and how workers can subvert this violence to create opportunities for future development

RIPK1-mediated immunogenic cell death promotes anti-tumour immunity against soft-tissue sarcoma.

Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cancer cells play an active role in inducing anti-tumour immunity but not every form of death can elicit an immune response. Moreover, resistance to apoptosis is a major problem in cancer treatment and disease control. While the term "immunogenic cell death" is not fully defined, activation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) can induce a type of death that mobilises the immune system against cancer. However, no clinical treatment protocols have yet been established that would harness the immunogenic potential of RIPK1. Here, we report the first pre-clinical application of an in vivo treatment protocol for soft-tissue sarcoma that directly engages RIPK1-mediated immunogenic cell death. We find that RIPK1-mediated cell death significantly improves local disease control, increases activation of CD8+ T cells as well as NK cells, and enhances the survival benefit of immune checkpoint blockade. Our findings warrant a clinical trial to assess the survival benefit of RIPK1-induced cell death in patients with advanced disease at limb extremities

Postsocialist disability matrix

This paper explores injustices experienced by disabled people in the postsocialist countries of Central and Eastern Europe. Drawing on Nancy Fraser’s theory of social justice, the analysis proposes a ‘matrix’ that reveals the negative impact of two factors – state socialist legacy and postsocialist neoliberalization – on disabled people’s parity of participation in three dimensions of justice – economic redistribution, cultural recognition, and political representation. The legacy of state socialism has underpinned: segregated service provision; medical-productivist understanding of disability for assessment purposes; denial of disability on everyday level; and weak disability organizing. Neoliberal restructuring has resulted in: retrenchment of disability support through decentralization, austerity, and workfare; stigmatization of ‘dependency’ through the discourse of ‘welfare dependency’; responsibilization of disabled people; and depoliticization of disability organizations by restricting their activities to service provision and incorporating them in structures of tokenistic participation. The analysis is informed by reports and academic studies of disability in the postsocialist region

Early predictors of language and social communication impairments at ages 9-11 years: A follow-up study of early-referred children

Purpose: In this study, the authors aimed to evaluate hypotheses that early sociocognition will predict later social communication and early phonology will predict later morphosyntax in clinically referred preschoolers. Method: Participants were 108 children ages 9–11 years who had been referred to clinical services with concerns about language at age 2½–3½ years. Predictors at Time 1 (T1) were measures of sociocognition, word/nonword repetition, and receptive language. Outcome measures at Time 3 (T3) included a social communication questionnaire completed by parents and tests of nonword repetition, morphosyntax, and receptive language. Results: Group- and case-level analyses revealed early sociocognition to be the strongest predictor of social communication problems, which by T3 affected almost one third of the sample. At the group level, early phonology, which was a significant problem for the majority of children at T1, was a weak predictor of morphosyntax at T3. However, at the case level the majority of children with poor morphosyntax and nonword repetition at outcome had had very low repetition scores at T1. Conclusions: In early language referrals, it is important to identify and address sociocognitive problems, a considerable risk for later social communication and autism spectrum disorders. The majority of early-referred children had phonological problems, often severe, but these require further investigation to determine their longer term significance for language

Genetically modified lentiviruses that preserve microvascular function protect against late radiation damage in normal tissues.

Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy (RT) are characterized by vascular dysfunction and fibrosis causing volume loss and tissue contracture, for example, in the free flaps used for immediate breast reconstruction after mastectomy. We evaluated the efficacy of lentivirally delivered superoxide dismutase 2 (SOD2) overexpression and connective tissue growth factor (CTGF) knockdown by short hairpin RNA in reducing the severity of LAEs in an animal model of free flap LAEs. Vectors were delivered by intra-arterial injection, ex vivo, to target the vascular compartment. LVSOD2 and LVshCTGF monotherapy before irradiation resulted in preservation of flap volume or reduction in skin contracture, respectively. Flaps transduced with combination therapy experienced improvements in both volume loss and skin contracture. Both therapies reduced the fibrotic burden after irradiation. LAEs were associated with impaired vascular perfusion, loss of endothelial permeability, and stromal hypoxia, which were all reversed in the treatment model. Using a tumor recurrence model, we showed that SOD2 overexpression in normal tissues did not compromise the efficacy of RT against tumor cells but appeared to enhance it. LVSOD2 and LVshCTGF combination therapy by targeted, intravascular delivery reduced LAE severities in normal tissues without compromising the efficacy of RT and warrants translational evaluation as a free flap-targeted gene therapy