57 research outputs found
'Kids sold, desperate moms need cash': Media representations of Zimbabwean women migrants
The article draws on 575 randomly selected articles from the South African Media database
to explore the representation of Zimbabwean women migrants. Using critical discourse analysis
(CDA), the article shows that some of the dominant construction types depict a picture of caricatured,
stereotypical and stigmatised Zimbabwean migrant women without voice and individuality. In turn,
the diversity of their actualities is not captured in the process of constructing the twin images of
Zimbabwean women as victims and as purveyors of decadent and other negative social ills in
society. We conclude that Zimbabwean women migrants appear in the SA media primarily in three
negative images: suppliers of sexual services, as un-motherly, and as victims. We also conclude
that there is need for media to capture the voices of migrant women recounting their everyday lived
experiences in different political and socio-economic contexts in order to account for the migrant
women's voices of resilience, defiance and victimhood and of agency, against the normalising and
marginalising influences of political institutions and national border controls. This would also help
capture the transformative nature of migration to the women, the 'home' in Zimbabwe and the 'home'
in South Africa.IS
IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System
PURPOSE:
To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application.
EXPERIMENTAL DESIGN:
HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use.
RESULTS:
TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality.
CONCLUSIONS:
Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471
Identifying barriers to the provision of bystander cardiopulmonary resuscitation (CPR) in high-risk regions: a qualitative review of emergency calls
© 2018 Elsevier B.V. Introduction: Understanding regional variation in bystander cardiopulmonary resuscitation (CPR) is important to improving out-of-hospital cardiac arrest (OHCA) survival. In this study we aimed to identify barriers to providing bystander CPR in regions with low rates of bystander CPR and where OHCA was recognised in the emergency call. Methods: We retrospectively reviewed emergency calls for adults in regions of low bystander CPR in the Australian state of Victoria. Included calls were those where OHCA was identified during the call but no bystander CPR was given. A thematic content analysis was independently conducted by two investigators. Results: Saturation of themes was reached after listening to 139 calls. Calls progressed to the point of compression instructions before EMS arrival in only 26 (18.7%) of cases. Three types of barriers were identified: procedural barriers (time lost due to language barriers and communication issues; telephone problems), CPR knowledge (skill deficits; perceived benefit) and personal factors (physical frailty or disability; patient position; emotional factors). Conclusion: A range of factors are associated with barriers to delivering bystander CPR even in the presence of dispatcher instructions – some of which are modifiable. To overcome these barriers in high-risk regions, targeted public education needs to provide information about what occurs in an emergency call, how to recognise an OHCA and to improve CPR knowledge and skills
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Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma.
PurposeIt has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short 1-week manufacture protocol to determine the feasibility, safety, and antitumor efficacy of this double cell therapy.Experimental designA clinical trial (NCT00910650) adoptively transferring MART-1 T-cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide-pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and reinfused with (n = 10) or without (n = 3) prior cryopreservation.ResultsA total of 14 patients with metastatic melanoma were enrolled and 9 of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared with cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using noncryopreserved T cells.ConclusionDouble cell therapy with ACT of TCR-engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses
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Adoptive Transfer of MART-1 T-Cell Receptor Transgenic Lymphocytes and Dendritic Cell Vaccination in Patients with Metastatic Melanoma
PurposeIt has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short 1-week manufacture protocol to determine the feasibility, safety, and antitumor efficacy of this double cell therapy.Experimental designA clinical trial (NCT00910650) adoptively transferring MART-1 T-cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide-pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and reinfused with (n = 10) or without (n = 3) prior cryopreservation.ResultsA total of 14 patients with metastatic melanoma were enrolled and 9 of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared with cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using noncryopreserved T cells.ConclusionDouble cell therapy with ACT of TCR-engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses
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