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Multiple Time Points (multiple + time_point)
Selected AbstractsA prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Margaret A. Gates Abstract Flavonoids are antioxidant compounds found in plants, including fruits, vegetables and tea. No prior prospective studies have examined the association between intake of flavonoids in the flavonol and flavone subclasses and ovarian cancer risk. We analyzed the association between intake of 5 common dietary flavonoids and incidence of epithelial ovarian cancer among 66,940 women in the Nurses' Health Study. We calculated each participant's intake of myricetin, kaempferol, quercetin, luteolin and apigenin from dietary data collected at multiple time points, and used Cox proportional hazards regression to model the incidence rate ratio (RR) of ovarian cancer for each quintile of intake. Our analysis included 347 cases diagnosed between 1984 and 2002, and 950,347 person-years of follow-up. There was no clear association between total intake of the 5 flavonoids examined and incidence of ovarian cancer (RR = 0.75 for the highest versus lowest quintile, 95% confidence interval [CI] = 0.51,1.09). However, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake (RR = 0.60, 95% CI = 0.42,0.87; p -trend = 0.002), and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake (RR = 0.66, 95% CI = 0.49,0.91; p -trend = 0.01). There was evidence of an inverse association with consumption of tea (nonherbal) and broccoli, the primary contributors to kaempferol intake in our population. These data suggest that dietary intake of certain flavonoids may reduce ovarian cancer risk, although additional prospective studies are needed to further evaluate this association. If confirmed, these results would provide an important target for ovarian cancer prevention. © 2007 Wiley-Liss, Inc. [source] The Alzheimer's disease neuroimaging initiative (ADNI): MRI methodsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2008Clifford R. Jack Jr. MD Abstract The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorodeoxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquiredat multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications thatguided protocol development. A major effort was devoted toevaluating 3D T1 -weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B1 -calibration scans when applicable; and an axial proton density-T2 dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc. [source] The effects of informative and non-informative price patterns on consumer price judgmentsPSYCHOLOGY & MARKETING, Issue 6 2006Shai Danziger Converging evidence from laboratory experiments and empirical models of scanner data suggests that product price evaluations are often based on a comparison to an internal reference price. Research indicates that the reference price may reflect various characteristics of previously encountered prices including the mean, the range, and the last price encountered. In this research, the authors test whether, for prices purportedly sampled over time, the reference price reflects temporal patterns of the price sequence (ascending and descending prices). In four studies, participants viewed prices purportedly sampled at one time point or at multiple time points and then evaluated a target price. Price distributions differed only in their temporal pattern, whereas the mean, the range, and in some conditions, the last price, were held constant. The results reveal that the price pattern does not affect price judgments when prices are purportedly sampled at one time point. However, for ascending and descending price sequences purportedly sampled over time, the price pattern affects price judgments. Based on these findings the authors propose that consumers flexibly select the internal reference price used for price evaluations. © 2006 Wiley Periodicals, Inc. [source] Comparing Methods of Measurement for Detecting Drug-Induced Changes in the QT Interval: Implications for Thoroughly Conducted ECG StudiesANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2004Nkechi E. Azie M.D. Background:,The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide. Methods:,Four methods were compared: (1) 12-lead simultaneous ECG (12-SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3-LEAD ECG using a manual tangential method, and (4) a computer-based, proprietary algorithm, 12SLÔ ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.25 and 0.5 mg. Changes in QT interval from baseline were calculated and compared across ECG methods, using Bland,Altman plots. Variability was studied using a mixed linear model. Results:,Baseline QT values differed between methods (range 376,395 ms), mainly based on the number of leads incorporated into the measurement, with LEAD II and 3-LEAD providing the shortest intervals. The 3-LEAD generated the largest QT change from baseline, whereas LEAD II and 12-SIM generated essentially identical result within narrow limits of agreement (0.4 ms mean difference, 95% confidence interval ± 20.5 ms). Variability with AUT (standard deviation 15.8 ms for within-subject values) was clearly larger than with 3-LEAD, LEAD II, and 12-SIM (9.6, 10.0, and 11.3 ms). Conclusion:,This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance. [source] LY2439821, a humanized anti,interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, double-blind, placebo-controlled, proof-of-concept studyARTHRITIS & RHEUMATISM, Issue 4 2010M. C. Genovese Objective We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti,interleukin-17 (anti,IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs). Methods This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10. Results Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821,combined groups (,2.3, ,2.4, and ,2.3, respectively) than in the placebo group (,1.7) at week 10 (P , 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events. Conclusion LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA. [source] Is there a relationship between skin erythema and fatigue in women undergoing irradiation after breast conserving surgery for early breast cancer?ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 4 2009A prospective study Abstract Aim: A prospective study was conducted to determine whether any relationship exits between skin erythema, fatigue and biological factors during and after adjuvant radiotherapy for early breast cancer. Methods: Breast erythema was assessed objectively using reflectance spectrophotometry. Fatigue was recorded utilising the functional assessment of cancer therapy fatigue subscale. A number of potential systemic indicators (biological factors) of the effects of radiotherapy was measured, including circulating cytokines, coagulation factors, peripheral blood indices and biochemistry. Measurements for erythema, fatigue and biological factors were taken at baseline and intervals during and following completion of radiotherapy. Results: A total of 52 eligible patients was included in the analysis. Breast erythema was shown to progressively increase during treatment, peaking on day 36 and returning to baseline by 4 months post-irradiation. Fatigue also progressively increased during treatment, reaching a plateau between day 22 and 2 weeks post-radiotherapy. A statistically significant association was demonstrated between total breast erythema and fatigue at days 4, 8, 22 and 29 of irradiation and 2 and 6 weeks post-radiotherapy. When only the increase in erythema attributable to radiotherapy was considered, statistically significant associations remained for day 4 of irradiation and 2 and 6 weeks post-radiotherapy. When multiple time points were considered together, an association between increased erythema and fatigue was present only post-radiotherapy. No relationship was demonstrated between the biological factors and erythema or fatigue during radiotherapy. Conclusion: This study demonstrates a significant and consistent relationship between radiotherapy-induced breast erythema and fatigue, particularly in the period immediately following breast irradiation. [source] Tumour Necrosis Factor Receptor 1 and Hepatocyte Regeneration in Acetaminophen Toxicity: A Kinetic Study of Proliferating Cell Nuclear Antigen and Cytokine ExpressionBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2005Laura P. James To examine the effects of tumour necrosis factor receptor 1 on hepatocyte regeneration, immunohistochemical staining with proliferating cell nuclear antigen was performed. Immunohistochemical staining for proliferating cell nuclear antigen was significantly reduced at multiple time points in the knock-out mice and did not normalize until 96 hr. To evaluate the effect of tumour necrosis factor receptor 1 depletion on cytokines known to be involved in regeneration, levels of macrophage inhibitory protein 2, interferon-,-inducible protein-10 and monocyte chemoattractant protein 1 were compared in the two groups of mice. Significant elevation of all cytokines was observed in both groups of mice; however, higher levels were present in the knock-out mice. Depletion of tumour necrosis factor receptor 1 has long-lasting effects on hepatocyte regeneration in acetaminophen toxicity but multiple other factors appear to orchestrate eventual recovery in these mice. [source] Latent Pattern Mixture Models for Informative Intermittent Missing Data in Longitudinal StudiesBIOMETRICS, Issue 2 2004Haiqun Lin Summary. A frequently encountered problem in longitudinal studies is data that are missing due to missed visits or dropouts. In the statistical literature, interest has primarily focused on monotone missing data (dropout) with much less work on intermittent missing data in which a subject may return after one or more missed visits. Intermittent missing data have broader applicability that can include the frequent situation in which subjects do not have common sets of visit times or they visit at nonprescheduled times. In this article, we propose a latent pattern mixture model (LPMM), where the mixture patterns are formed from latent classes that link the longitudinal response and the missingness process. This allows us to handle arbitrary patterns of missing data embodied by subjects' visit process, and avoids the need to specify the mixture patterns a priori. One assumption of our model is that the missingness process is assumed to be conditionally independent of the longitudinal outcomes given the latent classes. We propose a noniterative approach to assess this key assumption. The LPMM is illustrated with a data set from a health service research study in which homeless people with mental illness were randomized to three different service packages and measures of homelessness were recorded at multiple time points. Our model suggests the presence of four latent classes linking subject visit patterns to homeless outcomes. [source] High-Level Transient Production of a Heterologous Protein in Plants by Optimizing Induction of a Chemically Inducible Viral Amplicon Expression SystemBIOTECHNOLOGY PROGRESS, Issue 6 2007Michael A. Plesha We have demonstrated that the method of chemical induction using a chemically inducible viral amplicon expression system can be optimized to increase expression of a heterologous protein in plants. A cucumber mosaic virus inducible viral amplicon (CMViva) expression system was used to transiently produce a recombinant human blood protein, ,-1-antitrypsin (AAT), by co-infiltrating intact and detached Nicotiana benthamiana leaves with two Agrobacterium tumefaciens strains, one containing the CMViva expression cassette carrying the AAT gene and the other containing a binary vector carrying the gene silencing suppressor p19. Infiltrated plants were induced by either topical applications or pressure injections and inducer was applied at either a single or multiple time points. Applying induction solution every 2 days via topical application resulted in increasing maximum levels of biologically functional rAAT from 0.71% to 1.3% of the total soluble protein (TSP) in detached plant leaves, a 1.8-fold improvement. Multiple applications of induction solution via pressure injection into intact leaves resulted in maximum levels of biologically functional rAAT being elevated 3-fold up to 2.4% of TSP compared to 0.8% of TSP when using the conventional method of a single topical application, and expression levels remained high 6 days post-induction. Overall production of rAAT in intact leaves was found to have a maximum level of 5.8% of TSP or 390 mg rAAT per kg leaf tissue when applying multiple injections of chemical induction solution. [source] Neuropsychological symptom dimensions in bipolar disorder and schizophreniaBIPOLAR DISORDERS, Issue 1-2 2007Pál Czobor Background:, While neurocognitive (NC) impairments have been well documented in schizophrenia (SZ), there is limited data as to whether similar impairments are present in other persistent mental illnesses. Recent data indicate that NC impairments may be manifested in bipolar disorder (BPD) and that they persist across disease states, including euthymia. An important question is whether a comparable structure of NC impairments is present in the 2 diagnostic groups. Objective:, In a previous factor analytic study, we identified 6 factors to describe the basic underlying structure of neuropsychological (NP) functioning in SZ: Attention, Working Memory, Learning, Verbal Knowledge, Non-Verbal Functions, Ideational Fluency. The goal of this study was to investigate whether this factor structure is generalizable for BPD. Methods:, The BPD sample included patients (n = 155) from an ongoing longitudinal study evaluating BPD at the time of hospitalization for relapse and at multiple time points over the following 2 years. The SZ sample included patients (n = 250) from a 3-year study. For the current examination the baseline NP evaluations were selected for both samples. Results:, Exploratory and confirmatory factor analyses in the BPD sample yielded factors similar to those identified in the SZ sample. The coefficients of congruence ranged between 0.66,0.90 for the individual factors, indicating a good overall correspondence between the factor structures in the 2 diagnostic groups. Analysis of covariance (ANCOVA) analysis with education level, full scale-IQ, gender and ethnicity as covariates indicated that SZ patients had markedly worse performance on the Attention and Non-Verbal Functioning factors compared to the BPD patients. Conclusions:, Together, these data suggest that while the same underlying factor structure describes NP functioning in both groups, the profile of impairments appears to vary with the diagnosis. [source] Risk of tumour progression in early-stage hepatocellular carcinoma after radiofrequency ablationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2009M. L. Fernandes Background: This study aimed objectively to quantify the risk of tumour progression beyond the Milan criteria following radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) and to identify factors associated with tumour progression. Methods: Some 111 patients (136 tumours) with liver cirrhosis undergoing RF ablation for HCC within Milan criteria between February 2004 and June 2007 were enrolled in the study. Data were analysed retrospectively from a prospectively collected database. Results: The cumulative probability of tumour progression beyond the Milan criteria at 6, 12, 18, 24 and 36 months of RF ablation was 6·4, 11·0, 16·1, 21·2 and 44·8 per cent respectively. On multivariable analysis, factors independently associated with tumour progression were failure to achieve primary technique effectiveness (P = 0·005), ,-fetoprotein level above 200 ng/ml (P = 0·013) and Child,Pugh grade B cirrhosis (P = 0·034). Failure to achieve primary RF ablation technique effectiveness was associated with tumour location in segment VIII (P = 0·033), a cool-down temperature of 70 °C or less (P = 0·043) and multiple overlapping ablations (P = 0·029). Conclusion: This study provides clinicians with an objective risk of tumour progression beyond the Milan criteria after RF ablation at multiple time points. Primary technique failure is identified as a risk factor for tumour progression. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | ||||||||||