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

Inspirerende kolomstrategieën : lessen van buiten en binnen de agrarische sector

Vanwege de gewenste transitie naar duurzame landbouw zijn 6 inspirerende voorbeelden binnen en buiten de agrarische sector geanalyseerd op basis van eenzelfde theoretisch raamwerk. De resultaten van de analyse zijn vervolgens gebruikt in een workshop met primaire ondernemers die een trekkende rol vervullen in een aantal (over het algemeen nieuwe) agroketens. Dit heeft geleid tot een analyse van nog eens 7 casussen. Op basis van deze analyses worden aanbevelingen gedaan voor ondernemers en beleidsmaker

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Comparative Study of Different Methodologies for Fault Diagnosis in Multivariate Quality Control

Different methodologies for fault diagnosis in multivariate quality control have been proposed in recent years. These methods work in the space of the original measured variables and have performed reasonably well when there is a reduced number of mildly correlated quality and/or process variables with a well-conditioned covariance matrix. These approaches have been introduced by emphasizing their positive or negative virtues, generally on an individual basis, so it is not clear for the practitioner the best method to be used. This paper provides a comprehensive study of the performance of diverse methodological approaches when tested on a large number of distinct simulated scenarios. Our primary aim is to highlight key weaknesses and strengths in these methods as well as clarifying their relationships and the requirements for their implementation in practice.Vidal Puig, S.; Ferrer, A. (2014). A Comparative Study of Different Methodologies for Fault Diagnosis in Multivariate Quality Control. Communications in Statistics - Simulation and Computation. 43(5):986-1005. doi:10.1080/03610918.2012.720745S9861005435Arteaga, F., & Ferrer, A. (2010). How to simulate normal data sets with the desired correlation structure. Chemometrics and Intelligent Laboratory Systems, 101(1), 38-42. doi:10.1016/j.chemolab.2009.12.003Doganaksoy, N., Faltin, F. W., & Tucker, W. T. (1991). Identification of out of control quality characteristics in a multivariate manufacturing environment. Communications in Statistics - Theory and Methods, 20(9), 2775-2790. doi:10.1080/03610929108830667Fuchs, C., & Benjamini, Y. (1994). Multivariate Profile Charts for Statistical Process Control. Technometrics, 36(2), 182-195. doi:10.1080/00401706.1994.10485765Hawkins, D. M. (1991). Multivariate Quality Control Based on Regression-Adiusted Variables. Technometrics, 33(1), 61-75. doi:10.1080/00401706.1991.10484770Editorial Board. (2007). Computational Statistics & Data Analysis, 51(8), iii-v. doi:10.1016/s0167-9473(07)00125-9Hayter, A. J., & Tsui, K.-L. (1994). Identification and Quantification in Multivariate Quality Control Problems. Journal of Quality Technology, 26(3), 197-208. doi:10.1080/00224065.1994.11979526HOCHBERG, Y. (1988). A sharper Bonferroni procedure for multiple tests of significance. Biometrika, 75(4), 800-802. doi:10.1093/biomet/75.4.800HOMMEL, G. (1988). A stagewise rejective multiple test procedure based on a modified Bonferroni test. Biometrika, 75(2), 383-386. doi:10.1093/biomet/75.2.383Kourti, T., & MacGregor, J. F. (1996). Multivariate SPC Methods for Process and Product Monitoring. Journal of Quality Technology, 28(4), 409-428. doi:10.1080/00224065.1996.11979699Li, J., Jin, J., & Shi, J. (2008). Causation-BasedT2Decomposition for Multivariate Process Monitoring and Diagnosis. Journal of Quality Technology, 40(1), 46-58. doi:10.1080/00224065.2008.11917712Mason, R. L., Tracy, N. D., & Young, J. C. (1995). Decomposition ofT2 for Multivariate Control Chart Interpretation. Journal of Quality Technology, 27(2), 99-108. doi:10.1080/00224065.1995.11979573Mason, R. L., Tracy, N. D., & Young, J. C. (1997). A Practical Approach for Interpreting Multivariate T2 Control Chart Signals. Journal of Quality Technology, 29(4), 396-406. doi:10.1080/00224065.1997.11979791Murphy, B. J. (1987). Selecting Out of Control Variables With the T 2 Multivariate Quality Control Procedure. The Statistician, 36(5), 571. doi:10.2307/2348668Rencher, A. C. (1993). The Contribution of Individual Variables to Hotelling’s T 2 , Wilks’ Λ, and R 2. Biometrics, 49(2), 479. doi:10.2307/2532560Roy, J. (1958). Step-Down Procedure in Multivariate Analysis. The Annals of Mathematical Statistics, 29(4), 1177-1187. doi:10.1214/aoms/1177706449Runger, G. C., Alt, F. B., & Montgomery, D. C. (1996). Contributors to a multivariate statistical process control chart signal. Communications in Statistics - Theory and Methods, 25(10), 2203-2213. doi:10.1080/03610929608831832Sankoh, A. J., Huque, M. F., & Dubey, S. D. (1997). Some comments on frequently used multiple endpoint adjustment methods in clinical trials. Statistics in Medicine, 16(22), 2529-2542. doi:10.1002/(sici)1097-0258(19971130)16:223.0.co;2-jTukey, J. W., Ciminera, J. L., & Heyse, J. F. (1985). Testing the Statistical Certainty of a Response to Increasing Doses of a Drug. Biometrics, 41(1), 295. doi:10.2307/253066

A Two-Gene Signature, SKI and SLAMF1, Predicts Time-to-Treatment in Previously Untreated Patients with Chronic Lymphocytic Leukemia

We developed and validated a two-gene signature that predicts prognosis in previously-untreated chronic lymphocytic leukemia (CLL) patients. Using a 65 sample training set, from a cohort of 131 patients, we identified the best clinical models to predict time-to-treatment (TTT) and overall survival (OS). To identify individual genes or combinations in the training set with expression related to prognosis, we cross-validated univariate and multivariate models to predict TTT. We identified four gene sets (5, 6, 12, or 13 genes) to construct multivariate prognostic models. By optimizing each gene set on the training set, we constructed 11 models to predict the time from diagnosis to treatment. Each model also predicted OS and added value to the best clinical models. To determine which contributed the most value when added to clinical variables, we applied the Akaike Information Criterion. Two genes were consistently retained in the models with clinical variables: SKI (v-SKI avian sarcoma viral oncogene homolog) and SLAMF1 (signaling lymphocytic activation molecule family member 1; CD150). We optimized a two-gene model and validated it on an independent test set of 66 samples. This two-gene model predicted prognosis better on the test set than any of the known predictors, including ZAP70 and serum β2-microglobulin

Synaptogyrin-3 mediates presynaptic dysfunction induced by Tau

Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau

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

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