25 research outputs found

    At the Intersection of Ableism Entelechy, and Policy Debate

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    This article investigates the causes of ableism and inaccessibility in policy debate, and also envisions alternatives to the current conception of debate that could open doors to more participants at all levels of ability. We argue that the rhetorical theories of Kenneth Burke help to illuminate symbolic practices in debate which function to exclude disabled voices. We also forward the argument that the competitive nature of policy debate, along with its dominant discursive practices and speech codes, constitutes an example of what Kenneth Burke calls ‘entelechy’. We further argue that the entelechial nature of policy debate is at the root of ableism in the activity. Finally, we further employ Burke’s theory of the comic frame to elucidate how the institutions and individuals in the policy debate community might engage in self-reflection as a way to generate fresh approaches to the problem of ableism and exclusion in policy debate

    Impaired platelet-dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro.

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    BACKGROUND: Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-dependent TG over and above that of simple replacement therapy. OBJECTIVE: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia. METHODS: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels). RESULTS: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG. CONCLUSIONS: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation

    Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

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    The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

    Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

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    OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

    Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

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    The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

    Malaya, 1948: Britain’s Asian Cold War?

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    Between 8:30 and 9:00 a.m. on 16 June 1948, three Europeans were shot dead in the Sungei Siput area of Perak in northern Malaya. The three were estate managers of rubber plantations, and the perpetrators were guerrillas in the “mobile corps” of the Malayan Communist Party (MCP). The shootings were the culmination of a long series of attacks and “outrages” against estate managers in Penang, Selangor, and the southern state of Johore. Late that afternoon, the colonial government declared a state of emergency in Perak and Johore that was extended, two days later, to the whole ofMalaya. An immediate casualty was respect for civil liberties. Under emergency regulations the authorities enacted a range of draconian measures, including a ban on “seditious” publications; the introduction of coercive powers of detention, arrest, trial, deportation, and “banishment”; the establishment of the death penalty for anyone carrying unauthorized ÂȘrearms; and the registration of the entire adult population

    Impaired platelet dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro

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    Impaired thrombin generation (TG) is seen in patients with acquired coagulopathy, due to a combination of low coagulation factors and decreased platelet count (thrombocytopenia). Low coagulation factors seen in acquired coagulopathy are typically treated with plasma and occasionally with prothrombin complex concentrates (PCCs), and the decreased platelet count can be treated with platelet transfusions. Our study investigated the influence of PCCs on impaired generation of thrombin in the above context. Generation of adequate thrombin is crucial for the formation of a stable blood clot. We conclude that further clinical studies would be of interest to investigate the role of PCCs in the management of complex coagulopathy characterized by abnormal coagulation and mild-to-moderate thrombocytopenia
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