Cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg(-1) in anaesthetized patients, paralysed with vecuronium

We have studied, in adult patients, ASA I-II, the cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg(-1). After induction, patients were paralysed with vecuronium and the trachea intubated. Heart rate (HR) and non-invasive mean arterial pressure (MAP) were measured every 1 min. After stabilization of HR and MAP, defined a

Language Policy, Politics and Ideology in Mewat: Comparative Case Studies of Mewati in Two School Types

Recent years have witnessed a growing interest in multilingualism, language maintenance and managing language diversity both inside and outside the educational context. However, much of this work, especially in the educational context, has focused on (minority) languages and relatively little attention has been paid to ‘dialects’. This study explores the status and role of Mewati, a dialect generally subsumed under Hindi (Government of India, 2001) in schools. While Mewati is spoken by most Meos as their first language (Srivastava, 2011, p. 250), there are currently no studies that examine the use and role of Mewati in education in Mewat. This thesis addresses an important gap in understanding what roles are assigned (or not) to local dialects in education. This project was guided by two research questions: What language-in-education policies (LiEPs) were in place in the two types of schools (rural and urban) chosen for this study; and what role did Mewati play in the overall language policy framework in these schools. The goal of this project was to develop an understanding about how teachers comprehended, negotiated and implemented LiEPs within classrooms. It also aimed at uncovering and critically analysing the underlying ideologies, policies and political processes that informed and influenced these LiEPs in the two schools studied and how these policies, affected the position of Mewati in these schools. The schools studied differed across multiple dimensions including medium of instruction, board of affiliation, textbooks and curricula, location, infrastructure and the socio-economic background of the students. However, they were similar in that most students in both schools spoke Mewati as their home language. The case study was based on data collected in interviews, informal conversations, artifacts, documents and field notes. The data was gathered from both Meo and non-Meo teachers, who differed across linguistic, ethnic and religious lines, in order to obtain a richer and holistic perspective on teachers’ views and practices. This project took an interdisciplinary approach and drew insights from sociolinguistics, applied linguistics, education and sociology. The study draws significantly on Spolsky’s (2004) model of language policy which was used both as an analytical framework as well as a tool for organizing data. The study revealed that the LiEP of the rural schools was largely Hindi monolingual and the urban school mostly Hindi-English bilingual. Both types of schools failed to make space for Mewati, the mother tongue of the majority of students. In both school types, Hindi was taught as the first language. The majority of teachers also held negative attitudes towards Mewati. The teachers perceived Mewati as a hindrance for the learning and overall development of students. There was a significant communication gap between teachers and students particularly in the early years of education. There was also a severe shortage of local Meo teachers. Most teachers in both schools were non-Meos who could not speak Mewati. A complex mix of inter-ethnic relations between these groups and the socio-historical and political structures greatly influenced language choice patterns and policy decisions. This study has important implications for the role of mother tongue in education for policymakers, government officials, educationists, and teachers as the findings indicate a need for change in language policy and procedures

The Emerging Role of Ofatumumab in the Treatment of Chronic Lymphocytic Leukemia

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. Our better understanding of disease biology and risk stratification has allowed delivering more effective therapies. In fact, front-line chemoimmunotherapy has demonstrated improvement in overall survival when compared to chemotherapy in randomized studies. Yet, treatment of relapsed CLL remains challenging and few agents are effective in that setting. Ofatumumab (Ofa) is a humanized monoclonal antibody targeted against CD20 with demonstrable activity in rituximab-resistant CLL cell lines. This agent was recently approved for the treatment of relapsed/refractory CLL patients who have failed fludarabine and alemtuzumab. In this review, we provide a historical perspective on approaches to CLL as front-line and in the relapsed setting. We further summarize novel anti-CD20 antibodies with specific emphasis on ofa. We review studies that led to ofatumumab’s approval including pre-clinical data, trials using ofa in combination therapies, and adverse events/toxicities reported with this agent

Musical Minds:Attentional Blink Reveals Modality-Specific Restrictions

Formal musical training is known to have positive effects on attentional and executive functioning, processing speed, and working memory. Consequently, one may expect to find differences in the dynamics of temporal attention between musicians and non-musicians. Here we address the question whether that is indeed the case, and whether any beneficial effects of musical training on temporal attention are modality specific or generalize across sensory modalities.When two targets are presented in close temporal succession, most people fail to report the second target, a phenomenon known as the attentional blink (AB). We measured and compared AB magnitude for musicians and non-musicians using auditory or visually presented letters and digits. Relative to non-musicians, the auditory AB was both attenuated and delayed in musicians, whereas the visual AB was larger. Non-musicians with a large auditory AB tended to show a large visual AB. However, neither a positive nor negative correlation was found in musicians, suggesting that at least in musicians, attentional restrictions within each modality are completely separate.AB magnitude within one modality can generalize to another modality, but this turns out not to be the case for every individual. Formal musical training seems to have a domain-general, but modality-specific beneficial effect on selective attention. The results fit with the idea that a major source of attentional restriction as reflected in the AB lies in modality-specific, independent sensory systems rather than a central amodal system. The findings demonstrate that individual differences in AB magnitude can provide important information about the modular structure of human cognition

Update in the management of chronic lymphocytic leukemia

Advances in the treatment of chronic lymphocytic leukemia (CLL) have improved initial overall response (OR) rates, complete response (CR) rates and progression free survival (PFS). Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22) and del(17p13). The 2008 American Society of Hematology (ASH) Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophosphamide (FCR) significantly improved OR, CR and PFS. The improvement in PFS directly resulted from an improved ability to eliminate minimal residual disease (MRD) in the peripheral blood, highlighting the importance of MRD eradication. However, a multi-center study suggested that the high CR rates to chemoimmunotherapy regimens such as FCR obtained in academic centers may not be reproducible when the same regimens are given in the community setting. The immunomodulatory drug lenalidomide is active in relapsed high-risk CLL, but two studies of lenalidomide in previously untreated CLL patients failed to achieve a CR and were associated with significant tumor lysis, tumor flare and hematologic toxicity. In the relapsed setting, a combination study of the bifunctional alkylator bendamustine and rituximab (BR) demonstrated a high OR rate in patients with del(11q22) and del(17p13), indicating that further studies to define's bendamustine activity are warranted in high-risk CLL. Similarly, the CDK inhibitor flavopiridol demonstrated significant clinical activity and durable remissions in heavily treated, refractory CLL patients with high-risk cytogenetic features and bulky lymphadenopathy. The monoclonal anti-CD20 antibody ofatumumab appeared to be superior to rituximab in relapsed CLL patients with bulky nodal disease or high-risk cytogenetic features. Ongoing studies of these agents and other novel therapeutic agents in clinical development hold forth the promise that treatment options for CLL patients will continue to expand and improve

RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences

The chronic lymphocytic leukemia (CLL) armamentarium has evolved significantly, with novel therapies that inhibit Bruton Tyrosine Kinase, PI3K delta and/or the BCL2 protein improving outcomes. Still, the clinical course of CLL patients is highly variable and most previously recognized prognostic features lack the capacity to predict response to modern treatments indicating the need for new prognostic markers. In this study, we identified four epigenetically distinct proteomic signatures of a large cohort of CLL and related diseases derived samples (n = 871) using reverse phase protein array technology. These signatures are associated with clinical features including age, cytogenetic abnormalities [trisomy 12, del(13q) and del(17p)], immunoglobulin heavy-chain locus (IGHV) mutational load, ZAP-70 status, Binet and Rai staging as well as with the outcome measures of time to treatment and overall survival. Protein signature membership was identified as predictive marker for overall survival regardless of other clinical features. Among the analyzed epigenetic proteins, EZH2, HDAC6, and loss of H3K27me3 levels were the most independently associated with poor survival. These findings demonstrate that proteomic based epigenetic biomarkers can be used to better classify CLL patients and provide therapeutic guidance

Photoswitchable diacylglycerols enable optical control of protein kinase C.

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling