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PubMed1996

PhenoDB: an integrated client/server database for linkage and population genetics.

In this paper we describe PhenoDB, an Internet-accessible client/server database application for population and linkage genetics. PhenoDB stores genetic marker data on pedigrees and populations. A database for population and linkage genetics requires two core functions: data management tasks, such as interactive validation during data entry and editing, and data analysis tasks, such as generating summary population statistics and performing linkage analyses. In PhenoDB we attempt to make these tasks as easy as possible. The client/server architecture allows efficient management and manipulation of large datasets via an easy-to-use graphical interface. PhenoDB data (73 populations, 34 pedigrees, approximately 4200 individuals, and close to 80,000 typings) are stored in a generic format that can be readily exported to (or imported from) the file formats required by various existing analysis programs such as LIPED and Lathrop and Lalouel's Multipoint Linkage. PhenoDB allows performance of complex ad-hoc queries and can generate reports for use in project management. Finally, PhenoDB can produce statistical summaries such as allele frequencies, phenotype frequencies, and Chi-square tests of Hardy-Weinberg ratios of population/pedigree data.

Alleles↗
PubMed2002

Model-based cluster analysis of microarray gene-expression data.

BACKGROUND: Microarray technologies are emerging as a promising tool for genomic studies. The challenge now is how to analyze the resulting large amounts of data. Clustering techniques have been widely applied in analyzing microarray gene-expression data. However, normal mixture model-based cluster analysis has not been widely used for such data, although it has a solid probabilistic foundation. Here, we introduce and illustrate its use in detecting differentially expressed genes. In particular, we do not cluster gene-expression patterns but a summary statistic, the t-statistic. RESULTS: The method is applied to a data set containing expression levels of 1,176 genes of rats with and without pneumococcal middle-ear infection. Three clusters were found, two of which contain more than 95% genes with almost no altered gene-expression levels, whereas the third one has 30 genes with more or less differential gene-expression levels. CONCLUSIONS: Our results indicate that model-based clustering of t-statistics (and possibly other summary statistics) can be a useful statistical tool to exploit differential gene expression for microarray data.

Animals↗
PubMedDate not supplied

Chemotherapy response rates in recurrent/progressive pediatric glioma; results of a systematic review.

The optimum treatment strategy for recurrent childhood glioma is unknown. This report presents a systematic analysis of the currently available clinical data on chemotherapeutic management of this disease. A study protocol was prospectively developed outlining the objectives and methods of analysis including literature search strategy, eligibility criteria for published trials to be included, key data elements to be extracted and a plan for statistical analysis. Summary statistics were analyzed for the primary outcome variables. Data on recognized prognostic factors were recorded in order to adjust the outcome measures for these factors. A total of 27 non-randomized clinical trails were included in the analysis. Studies were stratified into 6 chemotherapy classes based on the frequency of drug used across studies. Average median response (complete + partial) across all drug categories was approximately 14% (range 10.4-23.5%). Adding patients with stable disease to complete and partial responders at least doubled average median response rates. Time to tumor progression ranged from 29.4 weeks to 49.7 weeks. The most frequently used drugs were the platinum analogs which demonstrated a mean TTP of 42.0 = /-23.4 weeks. Small sample sizes and the overall poor quality of the available data precluded definitive conclusions regarding the clinical impact of the various drug classes on the natural history of this disease.

Adolescent↗
PubMed2000

Analysis of a cluster randomized trial with binary outcome data using a multi-level model.

The use of multi-level logistic regression models was explored for the analysis of data from a cluster randomized trial investigating whether a training programme for general practitioners' reception staff could improve women's attendance at breast screening. Twenty-six general practices were randomized with women nested within them, requiring a two-level model which allowed for between-practice variability. Comparisons were made with fixed effect (FE) and random effects (RE) cluster summary statistic methods, ordinary logistic regression and a marginal model based on generalized estimating equations with robust variance estimates. An FE summary statistic method and ordinary logistic regression considerably understated the variance of the intervention effect, thus overstating its statistical significance. The marginal model produced a higher statistical significance for the intervention effect compared to that obtained from the RE summary statistic method and the multi-level model. Because there was only a moderate number of practices and these had unbalanced cluster sizes, reliable asymptotic properties for the robust standard errors used in the marginal model may not have been achieved. While the RE summary statistic method cannot handle multiple covariates easily, marginal and multi-level models can do so. In contrast to multi-level models however, marginal models do not provide direct estimates of variance components, but treat these as nuisance parameters. Estimates of the variance components were of particular interest in this example. Additionally, parametric bootstrap methods within the multi-level model framework provide confidence intervals for these variance components, as well as a confidence interval for the effect of intervention which allows for the imprecision in the estimated variance components. The assumption of normality of the random effects can be checked, and the models extended to investigate multiple sources of variability.

Breast Neoplasms↗
PubMed1995

Application of the Poincaré plot to heart rate variability: a new measure of functional status in heart failure.

BACKGROUND: Conventional methods of quantifying heart rate variability using summary statistics have shown that decreased variability is associated with increased mortality in heart failure. However, many patients with heart failure have arrhythmias which make the 'raw' heart rate variability data less suitable for the use of summary statistical measures. AIMS: To examine the clinical potential of a new measure of heart rate variability data, presented by the Poincaré plot pattern, as an adjunct to the summary statistical measures of R-R interval variability. METHODS: We used the Poincaré plot pattern to display beat-to-beat heart rate variability data from a group of 23 patients with heart failure and compared them with data collected from 20 healthy age-matched control subjects. The data, which consists of 2000 consecutive R-R intervals, were gathered over 20-40 minutes while the subjects rested supine in a quiet darkened room. RESULTS: The morphological classification scheme proposed reflected the functional status of patients in heart failure. There was a significant difference (chi-square = 27.5, p < 0.0001) in the different pattern types between patients with NYHA Class I and II compared to patients with NYHA Class II and IV. All healthy subjects displayed a 'cluster' type of pattern characterised by normally distributed data. Sixteen of the 23 patients in heart failure also produced data which were normally distributed but the remaining seven produced data which required careful filtering to make them suitable for analysis using summary statistics, but which could be analysed by the Poincaré plot. CONCLUSIONS: The Poincaré plot pattern is a semi-quantitative tool which can be applied to the analysis of R-R interval data. It has potential advantages in that it allows assessment of data which are grossly non-Gaussian in distribution, and is a simple and easily implemented method which can be used in a clinical setting to augment the standard electrocardiogram to provide 'real time' visualisation of data.

Aged↗
PubMed2007

Ascertainment bias and the pattern of nucleotide diversity at the human ALDH2 locus in a Japanese population.

Many East Asian human populations harbor a high-frequency deficiency allele for the aldehyde dehydrogenase 2 (ALDH2) enzyme, a critical protein involved in the metabolism of ethanol. Here we use resequencing and long-range SNP haplotype data from a Japanese sample to test whether patterns of nucleotide diversity and linkage disequilibrium at this locus are compatible with a standard neutral model of evolution. Examination of the pattern of polymorphism at a locus such as this, where the frequency of a common allele is known a priori, introduces an ascertainment bias that must be corrected for in analyses of the frequency spectrum of polymorphisms. We apply a flexible and generally applicable simulation approach to correct for this bias in our ALDH2 data and, also, to explore the effect of bias on the commonly used summary statistics Tajima's D, Fu and Li's D, and Fay and Wu's H. Our study finds no evidence that the pattern of genetic variation at ALDH2 differs from that expected under a standard neutral model. However, our general examination of ascertainment bias indicates that a priori knowledge of segregating alleles greatly affects the expected distributions of summary statistics. Under many parameter combinations we find that ascertainment bias introduces an elevated rate of false positives when summary statistics are used to test for deviations from a standard neutral model. However, we also show that over a wide range of conditions the power of all summary statistics can be greatly increased by incorporating prior knowledge of segregating alleles.

Aldehyde Dehydrogenase↗
PubMed2026

Causal effect of chloride intracellular channel protein 5 on chronic periodontitis: A Mendelian randomization study.

This study aimed to evaluate the potential causal effect of chloride intracellular channel protein 5 (CLIC5) on the risk of chronic periodontitis (CP) using a Mendelian randomization (MR) approach. MR analysis was conducted utilizing publicly available summary statistics from genome-wide association studies summary statistics for CLIC5 and CP. Multiple MR methods, including inverse variance weighted, MR Egger, weighted median and weighted mode, were employed to estimate the causal effects. Sensitivity analyses, comprising leave-one-out and heterogeneity assessments were performed to evaluate the robustness of our findings. This MR analysis consistently revealed a negative association between CLIC5 and CP, with statistical significance achieved using the inverse variance weighted and weighted median methods. The concordant effect estimates obtained from all methodological approaches collectively indicated a potential protective effect of CLIC5 against CP. The sensitivity analyses further confirmed the robustness of these findings. This study provides genetic evidence suggesting a potential causal association between increased CLIC5 levels and decreased risk of CP. These findings augment the existing literature implicating chloride channel proteins in modulating the inflammatory processes pertinent to periodontal health. Further investigation is warranted to decipher the underlying biological mechanisms and to explore the potential of CLIC5 as a therapeutic target for CP.

Chloride Channels↗
PubMed2003

The effects of visual input on postural control of the lumbar spine in unstable sitting.

Postural control of the lumbar spine in unstable sitting was quantified through the analysis of the center of pressure (CoP) movement recorded by a force plate situated underneath a seat that incorporated a hemisphere. Thirteen healthy subjects were tested under conditions of increasing seat instability and elimination of visual input. The purpose of this study was to determine the relative effects of visual input and support surface instability on open and closed loop postural control mechanisms in sitting and to determine the association between traditional summary statistics and random walk analysis of CoP movement. The effects of the seat instability level and visual input on the CoP movement parameters were tested with a two-factor, repeated measures ANOVA (p<0.01). In all summary statistics CoP movement parameters increased significantly due to the seat instability level and lack of visual input. The random walk analysis identified two regions, short- and long-term, which has been postulated to represent open and closed loop control mechanism, respectively. While short-term scaling exponents were independent from visual input, CoP displacement in the short-term region was significantly increased in the eyes closed condition. Summary statistic of CoP total path length per second correlated highly with critical point coordinates and short-term diffusion coefficients. The CoP movement in the long-term region was consistent with a closed loop control mechanisms. The findings of visual influence on what is assumed as an open-loop control mechanism does not, at face value, support the hypothesis that two separate mechanisms are working to achieve postural control.

Adult↗
PubMed1987

A comparison of statistical outcome variables in extremely low birth weight infants.

Three different summary statistics of developmental outcome are described. These include the "handicap ratio" (handicapped individuals divided by survivors), the "handicap rate" (handicapped individuals divided by live births for that birth weight group), and the "handicaps per 10,000 live births" (handicapped individuals divided by 10,000 live births for a geographic region). An analysis of these statistics was undertaken using a sample of extremely low birth weight (ELBW) (less than 1,001 g) infants born in Hawaii during the period of 1975-1981. The results of this study showed a poor correlation between these summary statistics. The results suggest that these statistics represent different aspects of outcome in the ELBW infant. Suitable uses for each of these variables is discussed.

Birth Rate↗
PubMed2000

Postural control of trunk during unstable sitting.

A method for quantifying postural control of the lumbar spine during unstable sitting was developed. The unstable seat apparatus was equipped with leg and foot supports to isolate the control of the lumbar spine and trunk from the adjustments in the lower body joints. Polyester resin hemispheres with decreasing diameters were attached to the bottom of the seat to achieve increasing levels of task difficulty. The seat was placed on a force plate at the edge of a table and the participating subjects were instructed to maintain their balance while sitting on the seat. Coordinates of center of pressure (CoP) were recorded and quantified with summary statistics and random walk analysis. The CoP movement increased significantly with increased seat instability (task difficulty) (p<0.01). Stabilogram plots of the CoP movement revealed short and long-term regions consistent with the hypothesis that the two regions reflect open and closed-loop postural control mechanisms. Repeatability of the CoP parameters was excellent for the summary statistics and the short-term random walk coefficients (0.77<R<0.96). It was fair for the long-term diffusion coefficients (0.56<R<0.57) and poor for the long-term scaling exponents (0.14<R<0.40). Summary statistics of the CoP movement were positively correlated with body weight (0.69<R<0. 73) and the T9 to L4/L5 distance (0.43<R<0.54) of the subjects. This method can be applied to study the deficits in postural control of the lumbar spine in low-back pain population.

Adult↗
PubMed1998

"Summary measure" statistic for assessing the outcome of treatment trials in relapsing-remitting multiple sclerosis.

OBJECTIVES: To review the outcome measures commonly used in phase III treatment trials of relapsing-remitting multiple sclerosis and to introduce a method of data analysis which is clinically appropriate for the often reversible disability in this type of multiple sclerosis. METHODS: The conventional end point measures for disability change are inadequate and potentially misleading. Those using the disability difference between study entry and completion do not take into account serial data or disease fluctuations. Rigid definitions of "disease progression" based on two measurements of change in disability several months apart, do not assess worsening after the defined "end point", nor the significant proportion of erroneous "treatment failures" which result from subsequent recovery from relapses that outlast the end point. Assessing attacks merely by counting their frequency ignores the variation in magnitude and duration. These problems can be largely circumvented by integrating the area under a disability-time curve (AUC), a technique which utilises all serial measurements at scheduled visits and during relapses to summarise the total neurological dysfunction experienced by an individual patient on any particular clinical scale during a study period. CONCLUSIONS: The "summary measure" statistic AUC incorporates both transient and progressive disability into an overall estimate of the dysfunction that was experienced by a patient during a period of time. It is statistically more powerful and clinically more meaningful than conventional methods of assessing disability changes, particularly for trials which are too short to expect to disclose major treatment effects on irreversible disability in patients with a fluctuating disease.

Analysis of Variance↗
PubMed1997

Multiresolution statistical analysis of high-resolution digital mammograms.

A multiresolution statistical method for identifying clinically normal tissue in digitized mammograms is used to construct an algorithm for separating normal regions from potentially abnormal regions; that is, small regions that may contain isolated calcifications. This is the initial phase of the development of a general method for the automatic recognition of normal mammograms. The first step is to decompose the image with a wavelet expansion that yields a sum of independent images, each containing different levels of image detail. When calcifications are present, there is strong empirical evidence that only some of the image components are necessary for the purpose of detecting a deviation from normal. The underlying statistic for each of the selected expansion components can be modeled with a simple parametric probability distribution function. This function serves as an instrument for the development of a statistical test that allows for the recognition of normal tissue regions. The distribution function depends on only one parameter, and this parameter itself has an underlying statistical distribution. The values of this parameter define a summary statistic that can be used to set detection error rates. Once the summary statistic is determined, spatial filters that are matched to resolution are applied independently to each selected expansion image. Regions of the image that correlate with the normal statistical model are discarded and regions in disagreement (suspicious areas) are flagged. These results are combined to produce a detection output image consisting only of suspicious areas. This type of detection output is amenable to further processing that may ultimately lead to a fully automated algorithm for the identification of normal mammograms.

Algorithms↗
PubMed2025

BTS: a scalable Bayesian Tissue Score for prioritizing GWAS variants and their functional contexts across >1000s of omics datasets.

MOTIVATION: statistics from genome-wide association studies (GWAS) are widely used in fine-mapping and colocalization analyses to identify causal variants and their enrichment in functional contexts, such as affected cell types and genomic features. With the expansion of functional genomic (FG) datasets, which now include hundreds of thousands of tracks across various cell and tissue types, it is critical to establish scalable algorithms integrating thousands of diverse FG annotations with GWAS results. RESULTS: We propose BTS (Bayesian Tissue Score), a novel, highly efficient algorithm uniquely designed for (i) identifying affected cell types and functional elements (context-mapping) and (ii) fine-mapping potentially causal variants in a context-specific manner using large collections of cell type-specific FG annotation tracks. BTS leverages GWAS summary statistics and annotation-specific Bayesian models to analyze genome-wide annotation tracks, including enhancers, open chromatin, and histone marks. We evaluated BTS on GWAS summary statistics for immune and cardiovascular traits, such as Inflammatory Bowel Disease (IBD), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Coronary Artery Disease (CAD). Our results demonstrate that BTS is over 100&#xd7; more efficient in estimating functional annotation effects and context-specific variant fine-mapping compared to existing methods. Importantly, this large-scale Bayesian approach prioritizes both known and novel annotations, cell types, genomic regions, and variants and provides valuable biological insights into the functional contexts of these diseases. AVAILABILITY AND IMPLEMENTATION: Docker image is available at https://hub.docker.com/r/wanglab/bts with preinstalled BTS R package (https://bitbucket.org/wanglab-upenn/BTS-R) and BTS GWAS summary statistics analysis pipeline (https://bitbucket.org/wanglab-upenn/bts-pipeline).

Genome-Wide Association Study↗
PubMed2004

Pharmacotherapy for social phobia.

BACKGROUND: Social phobia (SP), or social anxiety disorder, is a prevalent and disabling disorder. There is growing evidence that SP is mediated by specific neurobiological factors, and increased interest in the use of medication in its treatment. OBJECTIVES: To assess the effects of pharmacotherapy for Social Phobia, and to determine whether particular classes of medication are more effective and/or acceptable than others in its treatment. SEARCH STRATEGY: Studies of the pharmacotherapy of SP were identified using literature searches of the Cochrane Depression, Anxiety & Neurosis Group (CCDAN) specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2004), MEDLINE (1966 to 2003) and PsycLit (1966 to 2003). In addition, published and unpublished RCTs were requested from SP researchers and pharmaceutical companies and additional studies of any language were sought in reference lists of retrieved articles. SELECTION CRITERIA: All RCTs of the pharmacotherapy of SP were considered for the review. DATA COLLECTION AND ANALYSIS: The quality of selected RCTs was independently assessed by 2 raters on the CCDAN Quality Rating Scale, with the same raters collating data on treatment response and SP symptom ratings. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class (SSRIs - selective serotonin reuptake inhibitors; MAOIs - Monoamine oxidase inhibitors; RIMAs - reversible inhibitors of monoamine oxidase A), from which dichotomous and continuous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken. MAIN RESULTS: 36 RCTs of a range of medications were included in the analysis (4268 participants), of which 26 were short-term (14 weeks or less). A funnel plot provided evidence of publication bias. Summary statistics for responder status (assessed using the Clinical Global Impressions scale change item (CGI-C)) from 25 short-term comparisons demonstrated superiority of various medication agents over placebo (relative risk of non-response (RR) = 0.63; 95% CI = 0.55, 0.72; random effects model). Response to treatment by serotonin reuptake inhibitors (N = 11; RR = 0.67; 95% CI = 0.59, 0.76), MAOIs (N = 3; RR = 0.43; 95% CI = 0.24, 0.76) and RIMAs (N = 6; RR = 0.74; 95% CI = 0.59, 0.91) supported the value of these agents. However, the SSRIs were significantly more effective than the RIMAs (Deeks' stratified test of heterogeneity (Deeks 2001): Qb = 29.82; p < 0.00001). Summary statistics for SP symptoms from 16 comparisons using the Liebowitz Social Anxiety Scale (LSAS) showed a statistically significant difference between medication and placebo (weighed mean difference = -15.56, 95%CI = -17.95, -13.16), with this effect once again most evident for the SSRIs. Medication was also significantly superior to placebo in reducing SP symptom clusters, comorbid depressive symptoms, and associated disability. The value of long-term medication treatment in treatment responders was supported by 3 comparisons from maintenance studies (relative risk of non-response = 0.58; 95% CI = 0.39, 0.85) and 5 comparisons from relapse prevention studies (relative risk of relapse = 0.33; 95% CI = 0.22, 0.49). REVIEWERS' CONCLUSIONS: This review provides evidence that medication can be effective in treating SP over the short term, with the strongest evidence of treatment efficacy observed amongst the SSRIs. Furthermore, the data support continued pharmacotherapy in medication responders over the longer-term. Nevertheless, the possibility of publication has to be acknowledged. Additional issues for future research include the use of medication in children and adolescents with SP, and in SP with comorbid psychiatric disorders.

Humans↗
PubMed2000

Pharmacotherapy for posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. By definition prior psychological trauma plays a causal role in the disorder, and psychotherapy is a widely accepted intervention. Nevertheless there is growing evidence that PTSD is characterized by specific psychobiological dysfunctions, and this has contributed to a growing interest in the use of medication in its treatment. OBJECTIVES: The authors aimed to undertake a systematic review of randomized controlled trials (RCTs) of the pharmacotherapy of posttraumatic stress disorder (PTSD) following the guidelines and using the software of the Cochrane Collaboration, and to provide an estimate of the effects of medication in this disorder. Secondary objectives were to explore questions about whether particular classes of medication are more effective and/or acceptable than others in the treatment of PTSD, and about which factors (clinical and methodological) predict response to pharmacotherapy. SEARCH STRATEGY: Studies of the pharmacotherapy of PTSD were identified using literature searches of MEDLINE (1966 to 1999, using the textwords posttraumatic, post-traumatic, medication, pharmacotherapy) and other electronic databases (PSYCLIT; National PTSD Center Pilots database; Dissertation Abstracts; Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register). In addition, published and unpublished RCTs were requested from PTSD researchers and pharmaceutical companies. An initial broad strategy was undertaken to find not only RCTs, but also open-label trials and reviews of the pharmacotherapy of PTSD; additional studies were sought in reference lists of retrieved articles and included studies in any language. SELECTION CRITERIA: All RCTs of PTSD (including both placebo controlled and comparative trials), whether published or unpublished, but completed prior to the end of 1999 were considered for the review. DATA COLLECTION AND ANALYSIS: Selected RCTs were independently assessed and collated by 2 raters, and Review Manager (RevMan) software was used to capture data on treatment response and PTSD symptom ratings. Ratings of subtypes of PTSD symptoms (intrusive/re-experiencing, avoidant/numbing, hyperarousal), of comorbid symptoms (depression, anxiety), and of quality of life were included where possible. A range of additional information, which may explain possible clinical and methodological heterogeneity amongst the trials, was also captured. Summary statistics for dichotomous and continous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken. MAIN RESULTS: 15 short-term (12 weeks or less) RCTs were found, of which 9 had sufficient data for inclusion in the analysis. Methodological limitations were particularly apparent in early work; these included short (5 weeks or less) duration of trials and a reliance on self-report scales (rather than use of standardized clinician-rated scales). Despite these and other potentially important differences between the trials, many trials demonstrated efficacy for medication over placebo. Summary statistics were calculated for the Clinical Global Impressions scale change item (CGI-C) or close equivalent from 10 sets of data including various antidepressants and other agents - the proportion of non-responders was lower in the pharmacotherapy group than in the control group (relative risk (95% CI) = 0.72 (0.64, 0.83)). Similarly, summary statistics for the intrusion, avoidance and total scales of the Impact of Events Scale (IES) from 4sets of data again including various agents showed a statistically (and clinically) significant difference between medication and placebo (Weighted Mean Difference (95% CI) = -3.81 (-6.72,-0.91), -3.31(-5.24,-1.37), -7.18 (-11.86,-2.50) respectively). REVIEWER'S CONCLUSIONS: Medication treatments can be effective in PTSD, acting to reduce its core symptoms, and should be considered as part of the treatment of this disorder. The existing evidence base does not provide sufficient data to suggest particular predictors of response to treatment, or to demonstrate that any particular class of medication is more effective or better tolerated than any other. However, the largest trials showing efficacy to date have been with the SSRIs, and in contrast, there have been negative studies of some agents. Given the high prevalence and enormous personal and societal costs of PTSD, there is a need for additional controlled trials in this area. Additional questions for future research include the effects of medication on quality of life in PTSD, appropriate dose and duration of medication, the use of medication in different trauma groups, in pediatric and geriatric subjects, and the value of early (prophylactic), combined (with psychotherapy), and long-term (maintenance) medication treatment.

Antidepressive Agents↗
PubMed1991

Dynamic characteristics of cardiac R-R intervals during sleep and waking states.

Traditional assessment of cardiac R-R intervals during sleep-wake states uses summary statistics such as mean and interquartile range. Such summary statistics are less able to provide information about instantaneous or dynamic aspects of beat-to-beat control. We examined state-dependent beat-to-beat patterning by plotting each cardiac R-R interval against the previous interval (Poincaré plots). This procedure provides an indication of the probability of occurrence of one interval from its predecessor and allows assessment of dynamic properties of R-R interval variation. Cardiac R-R intervals were determined over 5-12-minute periods of wakefulness (AW), quiet sleep (QS) and rapid eye movement sleep (REM) from six cats; each interval was plotted on the y-axis against the previous value on the x-axis resulting in an RRn + 1 vs. RRn plot. These plots provided evidence that the correlation between an interval and its successor was greater in REM than in QS, even though the overall range was greater in REM. The results suggest that short-term cardiac control during REM may be influenced by more closely regulated mechanisms than suggested by classic concepts.

Animals↗
PubMed2000

Antioxidant vitamin and mineral supplements for age-related macular degeneration.

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals produced in the process of light absorption. OBJECTIVES: The objective of this review is to assess the effects of antioxidant vitamin and/or mineral supplementation on the progression of age-related macular degeneration. SEARCH STRATEGY: The Cochrane Eyes and Vision Group specialised registered, the Cochrane Controlled Trials Register - Central, MEDLINE, the Science Citation Index, and the reference lists of relevant articles were searched. Investigators of included studies were contacted. The most recent searches were performed in December 1999. SELECTION CRITERIA: All randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control in people with age-related macular degeneration were included. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Due to the small number of trials identified, and variable methods of collecting and presenting outcome data, no statistical summary measure was calculated. MAIN RESULTS: Four published, two unpublished and two ongoing trials were identified. Published trials to date have been small and results inconsistent. Adverse effects and quality of life for people with age-related macular degeneration have not been addressed. REVIEWER'S CONCLUSIONS: The question as to whether people with age-related macular degeneration should take antioxidant vitamin or mineral supplements to prevent progression of the disease has not been answered by research to date. The results of ongoing trials are awaited.

Antioxidants↗