448 research outputs found

    Spectacular Suffering: the imprisoned body as an artefact of resistance

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    The spectacle of the body in pain has long functioned heuristically in crime and justice. Within this phenomenon sits a counter-cultural tradition of re-enacting outrages in public view to rally against injustices. This article starts from the established claim that bodily suffering comprises a core matter of humanitarian campaigning. However, if ‘spectacular suffering’ has predominantly been discussed as a visual experience, this article examines its performative aspects. Transgressive performance is evident in demonstrations of forced-feeding, hunger strikes, self-immolation and lip-sewing carried out by prisoners or by their intermediaries with a view to publicizing their cause. During such exhibitions, the body in pain becomes a heuristic device for converting suffering into a medium for public consumption. However, tropes of corporal suffering are susceptible to cultural contestation and resistance from spectators. These possibilities call the publicity of suffering into question as an inherently progressive strategy

    The effectiveness of a multi-pronged psycho-social intervention among people with mental health and epilepsy problems-a pre-post prospective cohort study set in North India

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    Background: In low-and middle-income settings, many people with mental health problems cannot or do not access psychiatric services. Few studies of people with epilepsy and mental problems have evaluated the effectiveness of a predominantly psycho-social intervention, delivered by lay community workers. The aim of this study was to assess the effectiveness of a community-based complex mental health intervention within informal urban communities while simultaneously addressing social determinants of mental health among disadvantaged people with severe and common mental disorders (CMDs), and epilepsy. Methods: In this observational, prospective cohort study set in Uttarakhand, India, the lay-worker led intervention included psychoeducation, behavioural activation, facilitation of access to care, and facilitated psycho-social support groups. Participants were categorised as having a severe or CMD or epilepsy and assessed 5 times over 24 months using primary outcome measures, including the Patient Health Questionnaire (PHQ9) (severity of depression), the World Health Organization Disability Assessment Schedule (WHODAS 2.0), the Recovery Star, and scoring of a bespoke Engagement Index. Analysis included descriptive statistics as well as hierarchical linear regression models to report fixed effects as regression coefficients. Results: Among the 297 (baseline) participants only 96 people (31%) regularly used psychotropic medication (at least 4 weeks) and over 60% could not or did not consult a psychiatrist at all in the study period. Nonetheless, people with CMDs showed a significant reduction in their depression severity (PHQ9: B =-6.94, 95% CI-7.37 to-6.51), while people with severe mental disorders (SMDs) showed a significant reduction in their disability score (WHODAS 2.0: B =-4.86, 95% CI-7.14 to-2.57). People with epilepsy also reduced their disability score (WHODAS 2.0: B =-5.22, 95% CI-7.29 to-3.15). Conclusion: This study shows significant improvements in mental health, depression, recovery, disability and social engagement for people with common and SMDs, and epilepsy, through a community-based intervention that was non-pharmaceutical. It provides preliminary evidence of the value of predominantly psycho-social interventions implemented by lay health workers among people with limited or no access to psychiatric services

    BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

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    B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception of some BCR-ABL1(+) patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for adult B-ALL patients and chemotherapy remains first-line therapy despite adverse side effects and poor efficacy. We show that, although the MEK/ERK pathway is activated in B-ALL cells driven by different oncogenes, MEK inhibition does not suppress B-ALL cell growth. However, MEK inhibition synergized with BCL-2/BCL-XL family inhibitors to suppress proliferation and induce apoptosis in B-ALL cells. We show that this synergism is mediated by the pro-apoptotic factor BIM, which is dephosphorylated as a result of MEK inhibition, allowing it to bind to and neutralize MCL-1, thereby enhancing BCL-2/BCL-XL inhibitor-induced cell death. This cooperative effect is observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential

    Double Dissociation of Amygdala and Hippocampal Contributions to Trace and Delay Fear Conditioning

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    A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures by trace conditioning alters the role of the amygdala compared to delay fear conditioning, where the CS and US overlap. To investigate this, we inactivated the amygdala of male C57BL/6 mice with GABA A agonist muscimol prior to 2-pairing trace or delay fear conditioning. Amygdala inactivation produced deficits in contextual and delay conditioning, but had no effect on trace conditioning. As controls, we demonstrate that dorsal hippocampal inactivation produced deficits in trace and contextual, but not delay fear conditioning. Further, pre- and post-training amygdala inactivation disrupted the contextual but the not cued component of trace conditioning, as did muscimol infusion prior to 1- or 4-pairing trace conditioning. These findings demonstrate that insertion of a temporal gap between the CS and US can generate amygdala-independent fear conditioning. We discuss the implications of this surprising finding for current models of the neural circuitry involved in fear conditioning
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