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Cumulative Data (cumulative + data)
Selected AbstractsPathogenesis of Brain and Spinal Cord Atrophy in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 2004Alireza Minagar MD ABSTRACT For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neuro logic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis. [source] Nonhomologous Robertsonian translocations (NHRTs) and uniparental disomy (UPD) risk: an Italian multicentric prenatal surveyPRENATAL DIAGNOSIS, Issue 8 2004A. Sensi Abstract Objectives The risk of uniparental disomy (UPD) occurrence associated with the prenatal finding of balanced nonhomologous Robertsonian translocations (NHRTs) has been estimated only on limited empirical data. The aim of the study was to verify the estimate of the general risk, to get narrower confidence intervals by cumulating the data and to obtain risk estimates for specific translocation types. Methods We tested for UPD 160 prenatal specimens referred to the participant centers after the cytogenetic finding of NHRT. Results One case of upd(14)mat was found, associated with a 45,XX,der(14;22)mat fetal karyotype. The general empirical risk of UPD occurrence in NHRT carrier fetuses, corrected for the actual number of chromosomes analyzed, was 0.76% (95% CI 0.02,4.25%). Cumulative data with previous studies gives a general risk of UPD associated with NHRT of 0.80% (95% CI 0.17,2.34%). The UPD risk for the specific NHRT der(13;14) did not significantly differ from that of the other NHRTs taken together. Conclusion The present survey confirms the previously estimated risk of occurrence of UPD in offspring of NHRT carriers as a low, but not negligible risk, worth being investigated in prenatal diagnosis. Copyright © 2004 John Wiley & Sons, Ltd. [source] From Adjuvant Therapy to Breast Cancer Prevention: BCPT and STARTHE BREAST JOURNAL, Issue 3 2001Barbara K. Dunn MD Abstract: The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events. [source] Dynamic macroecology on ecological time-scalesGLOBAL ECOLOGY, Issue 1 2010Jonathan A. D. Fisher ABSTRACT Aim, The discipline of macroecology is increasingly being regarded as an effective vehicle for the evaluation of recent population- to ecosystem-level responses to widespread human and environmental influences. However, due to the prevalent use of time-averaged and cumulative data in macroecological analyses, the majority of the patterns that emerge from research in this field can be regarded as static. Here we review the application of dynamic macroecological analyses to changes in relationships between macroecological variables on seasonal to decadal scales. We illustrate the strength of this perspective for documenting changing patterns and testing hypotheses related to these dynamics on ecological time-scales. Location, Studies were compiled and reviewed from terrestrial and aquatic ecosystems. Methods, We review examples of temporal changes in macroecological patterns driven by recent anthropogenic influences and environmental change. Results, The dynamic nature of macroecological patterns on ecological time-scales has been revealed in recent years across a wide range of ecosystems, largely through the development, maintenance and analysis of biotic and environmental monitoring time series. The resultant analyses complement examinations of dynamics over evolutionary time and have similarly revealed that static portrayals can conceal important temporal dynamics that underlie the patterns of interest. As a consequence, static depictions, resting as they do on comparative analyses in which the validity of space-for-time substitutions is assumed, may be of limited use for testing hypotheses related to the mechanisms underlying the patterns revealed and, by extension, the development of reliable predictions of future states. Main conclusions, Recent dynamic macroecological analyses have demonstrated the utility of combined spatial and temporal replication, and have contributed to hypothesis testing related to the mechanistic processes underlying changes in macroecological patterns on ecological time-scales. We suggest four specific avenues of future research to further the development and application of temporal approaches on similar time-scales within the field of macroecology. [source] Confidence in Religious Leaders in Korea: A Research NoteJOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION, Issue 2 2010Jibum Kim Korea may provide an important testing ground for assessing religious growth as a correlate of religious authority. In Korea from 1985 to 1995, all religious groups experienced growth, but from 1995 to 2005 only the Catholic population did so. Favorable images of Korean Catholicism compared to other Korean religions point to one factor that may account for this trend, namely, confidence in religious leaders. Up to now there has been no empirical test measuring confidence in religious leaders among different religious groups in Korea. Using the 2003,2007 Korean General Social Surveys cumulative data, we found a hierarchy of confidence in religious leaders ranging from highest to lowest as follows: Catholics, Protestants, Buddhists, no religion. Our finding may suggest the continued vitality of Catholicism in Korea. [source] Risks of allogeneic hand transplantationMICROSURGERY, Issue 2 2004Steffen Baumeister M.D. A patient undergoing allogeneic hand transplantation needs lifelong immunosuppression with the risk of serious side effects, including life-threatening disease. The question remains: does the eventual improvement in function justify the risk? To answer this question, we try to assess the risks based on a large body of cumulative data derived from more 200,000 kidney transplants using the Collaborative Transplantation Study (CTS). Only selective data which apply to a patient population aged between 15,40 years were used (n = 58,310). Data are compared to the literature references and show superiority with respect to patient numbers, statistics, actuality, and methodology. The CTS data show that the incidence of de novo malignancies is lower than previously reported. The risk of developing any form of cancer is approximately 3%, of developing a skin cancer 1.1%, and of developing a lymphoma 0.58% within 5 years after transplantation. The risk of suffering from a cataract is 11% after 5 years, which is also lower than previously reported. Although the incidence of side effects (particularly malignant disease) is likely to be lower than previously thought, the risk-benefit question must be answered by each hand surgeon for each individual patient. © 2004 Wiley-Liss, Inc. [source] Endothelin-1 gene polymorphism and hearing impairment in elderly JapaneseTHE LARYNGOSCOPE, Issue 5 2009Yasue Uchida MD Abstract Objectives/Hypothesis: To investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) in the endothelin-1 gene (EDN1) and hearing impairment in middle-aged and elderly Japanese. Study Design: Longitudinal study. Methods: Data were collected from community-dwelling Japanese adults who participated in the Longitudinal Study of Aging biennially between 1997 and 2006. The participants at baseline were 2,231 adults aged 40 years to 79 years. An average hearing threshold level of 25 dB or better in the better ear for frequencies 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was defined as no hearing impairment. Using generalized estimating equations to treat repeated observations within subjects, 7,097 cumulative data were analyzed to assess the association between hearing status and the EDN1 G/T polymorphism with adjustment for age, sex, histories of ear disease, occupational noise exposure, heart disease, hypertension, and body mass index under additive, dominant, and recessive genetic models. Results: Comparison with wild-type homozygotes (GG), heterozygotes, and mutant homozygotes (GT/TT) showed a positive association with hearing impairment after adjustment for age in model 1 (odds ratio [OR] = 1.24; 95% confidence interval [CI] = 1.02,1.50; P = .033), for age and sex in model 2 (OR = 1.29; CI = 1.06,1.57; P = .0122), and for age, sex, history of ear disease, and history of occupational noise exposure in model 3 (OR = 1.31; CI = 1.07,1.60; P = .0092). The association was also significant in model 3 under the additive model. Conclusions: This study demonstrated that mutant T-allele carriers were associated with a higher risk of hearing impairment than carriers of wild-type homozygotes in middle-aged and elderly people. This result implies that endothelin-1 plays a valuable role in the cochlea. Laryngoscope, 2009 [source] | |||||||||||||