Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Comparison of Pattern Detection Methods in Microarray Time Series of the Segmentation Clock

While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis. A method related to Fourier analysis, the Lomb-Scargle periodogram, was used to detect periodic profiles in the dataset, leading to the identification of a novel set of cyclic genes associated with the segmentation clock. Here, we applied to the same microarray time series dataset four distinct mathematical methods to identify significant patterns in gene expression profiles. These methods are called: Phase consistency, Address reduction, Cyclohedron test and Stable persistence, and are based on different conceptual frameworks that are either hypothesis- or data-driven. Some of the methods, unlike Fourier transforms, are not dependent on the assumption of periodicity of the pattern of interest. Remarkably, these methods identified blindly the expression profiles of known cyclic genes as the most significant patterns in the dataset. Many candidate genes predicted by more than one approach appeared to be true positive cyclic genes and will be of particular interest for future research. In addition, these methods predicted novel candidate cyclic genes that were consistent with previous biological knowledge and experimental validation in mouse embryos. Our results demonstrate the utility of these novel pattern detection strategies, notably for detection of periodic profiles, and suggest that combining several distinct mathematical approaches to analyze microarray datasets is a valuable strategy for identifying genes that exhibit novel, interesting transcriptional patterns

Comparison of the cellular cytotoxic activities of colostral lymphocytes and maternal peripheral blood lymphocytes

Colostral lymphocytes (CL) from mothers 2 to 4 days post-partum and autologous maternal peripheral blood lymphocytes (PBL) were investigated for (1) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (2) target binding ability, (3) interferon (IFN)- and interleukin 2 (IL2)-induced augmentation of NK activity, (4) lectin-dependent cellular cytotoxicity (LDCC), and (5) the ability of culture-derived soluble suppressor factor(s) to inhibit the NK activity of normal allogeneic lymphocytes. CL depleted of adherent cells and Percoll-separated NK-enriched subpopulations of CL demonstrated significantly lower NK and ADCC activities compared to autologous PBL. However, the target binding ability of CL was comparable to autologous PBL. Although the residual NK activity of CL was augmented by IFN and IL2, the activity was not enhanced to the same level shown by autologous PBL. CL also demonstrated a significant enhancement of LDCC activity, although the activity was not stimulated to the levels shown by PBL. Culture supernates of CL manifested greater suppression of the NK ability of allogeneic PBL than culture supernates produced by autologous PBL. These results are consistent with a model that suggests differential partitioning of lymphocyte subpopulations between colostrum and peripheral blood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25675/1/0000228.pd

Risk Adjustment and Outcome Measures for Out-of-hospital Respiratory Distress

: The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work, this group delineated the priority conditions, described conceptual models, suggested core and risk adjustment measures potentially useful to emergency medical services research, and summarized out-of-hospital pain measurement. In this fifth article in the EMSOP series, the authors recommend specific risk-adjustment measures and outcome measures for use in out-of-hospital research on patients presenting with respiratory distress. The methodology included systematic literature searches and a structured review by an expert panel. The EMSOP group recommends use of pulse oximetry, peak expiratory flow rate, and the visual analog dyspnea scale as potential risk-adjustment measures and outcome measures for out-of-hospital research in patients with respiratory distress. Furthermore, using mortality as an outcome measure is also recommended. Future research is needed to alleviate the paucity of validated tools for out-of-hospital outcomes research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73779/1/j.aem.2004.03.010.pd

Establishing the Scope and Methodological Approach to Out-of-hospital Outcomes and Effectiveness Research

: Outcomes research offers out-of-hospital medicine a valuable methodology for studying the effectiveness of services provided in the out-of hospital setting. A clear understanding of the history and constructs of outcomes research is necessary for its integration into emergency medical services research. This report describes the conceptual framework of outcomes research and key methodological considerations for the successful implementation of out-of-hospital outcomes research. Illustrations of the specific applications of outcomes research and implications to existing methodologies are given, as well as suggestions for improved interdisciplinary research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75033/1/j.aem.2004.04.014.pd

Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy

To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration’s role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist’s role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy

Relation Between Gender, Etiology and Survival in Patients With Symptomatic Heart Failure

OBJECTIVES: This study investigated the relation between gender, etiology and survival in patients with symptomatic heart failure. BACKGROUND: Previous work provides conflicting results concerning the relation between gender, clinical characteristics and survival in patients with heart failure. METHODS: We examined the relation of these factors in 557 patients (380 men, 177 women) who had symptomatic heart failure, predominantly nonischemic in origin (68%) and typically associated with severe left ventricular dysfunction. RESULTS: Follow-up data were available in 99% of patients (mean follow-up period 2.4 years, range 1 day to 10 years) after study entry, and 201 patients reached the primary study end point of all-cause mortality. By life-table analysis, women were significantly less likely to reach this primary end point than men (p < 0.001). A significant association was found between female gender and better survival (p < 0.001), which depended on the primary etiology of heart failure (p = 0.008 for the gender-etiology interaction) but not on baseline ventricular function. Women survived longer than men when heart failure was due to nonischemic causes (men vs. women: relative risk [RR] 2.36, 95% confidence interval [CI] 1.59 to 3.51, p < 0.001). In contrast, outcome appeared similar when heart failure was due to ischemic heart disease (men vs. women: RR 0.85, 95% CI 0.45 to 1.61, p = 0.651). CONCLUSIONS: Women with heart failure due to nonischemic causes had significantly better survival than men with or without coronary disease as their primary cause of heart failure

Heterostructures for High Performance Devices

Contains an introduction and reports on ten research projects.Charles S. Draper Laboratory, Contract DL-H-315251Joint Services Electronics Program, Contract DAAL03-89-C-0001National Science Foundation Grant, Grant EET 87-03404MIT FundsInternational Business Machines CorporationNational Science Foundation Grant ECS 84-1317

Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)

The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure