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At least 991 records · Page 55Linked to original sources
PubMed2001

Replication validity of genetic association studies.

The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale. Meta-analysis provides a quantitative approach for combining the results of various studies on the same topic, and for estimating and explaining their diversity. Here, we have evaluated by meta-analysis 370 studies addressing 36 genetic associations for various outcomes of disease. We show that significant between-study heterogeneity (diversity) is frequent, and that the results of the first study correlate only modestly with subsequent research on the same association. The first study often suggests a stronger genetic effect than is found by subsequent studies. Both bias and genuine population diversity might explain why early association studies tend to overestimate the disease protection or predisposition conferred by a genetic polymorphism. We conclude that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.

Bias↗
PubMed2006

Prediction of molecular alignment of nucleic acids in aligned media.

We demonstrate--using the data base of all deposited DNA and RNA structures aligned in Pf1-medium and RDC refined--that for nucleic acids in a Pf1-medium the electrostatic alignment tensor can be predicted reliably and accurately via a simple and fast calculation based on the gyration tensor spanned out by the phosphodiester atoms. The rhombicity is well predicted over its full range from 0 to 0.66, while the alignment tensor orientation is predicted correctly for rhombicities up to ca. 0.4, for larger rhombicities it appears to deviate somewhat more than expected based on structural noise and measurement error. This simple analytical approach is based on the Debye-Huckel approximation for the electrostatic interaction potential, valid at distances sufficiently far away from a poly-ionic charged surface, a condition naturally enforced when the charge of alignment medium and solute are of equal sign, as for nucleic acids in a Pf1-phage medium. For the usual salt strengths and nucleic acid sizes, the Debye-Huckel screening length is smaller than the nucleic acid size, but large enough for the collective of Debye-Huckel spheres to encompass the whole molecule. The molecular alignment is then purely electrostatic, but it's functional form is under these conditions similar to that for steric alignment. The proposed analytical expression allows for very fast calculation of the alignment tensor and hence RDCs from the conformation of the nucleic acid molecule. This information provides opportunities for improved structure determination of nucleic acids, including better assessment of dynamics in (multi-domain) nucleic acids and the possibility to incorporate alignment tensor prediction from shape directly into the structure calculation process. The procedures are incorporated into MATLAB scripts, which are available on request.

Bacteriophage Pf1↗
PubMed1986

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF.

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.

Adolescent↗
PubMed2002

Progressive motion of an ac-driven kink in an annular damped system.

A novel dynamical effect is presented: systematic drift of a topological soliton in ac-driven weakly damped systems with periodic boundary conditions. The effect is demonstrated in detail for a long annular Josephson junction. Unlike earlier considered cases of the ac-driven motion of fluxons (kinks), in the present case the long junction is spatially uniform. Numerical simulations reveal that progressive motion of the fluxon commences if the amplitude of the ac drive exceeds a threshold value. The direction of the motion is randomly selected by initial conditions, and a strong hysteresis is observed. An analytical approach to the problem is based on consideration of the interaction between plasma waves emitted by the fluxon under the action of the ac drive and the fluxon itself, after the waves complete round trip in the annular junction. The analysis predicts instability of the zero-average-velocity state of the fluxon interacting with its own radiation tails, provided that the drive's amplitude exceeds an explicitly found threshold. The result is valid if the phase shift phi of the radiation wave, gained after the round trip, is such that sin phi<0, the threshold amplitude strongly depending on phi. A very similar dependence is found in the simulations, testifying to the relevance of the analytical consideration.

Journal Article↗
PubMed2006

Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5.

BACKGROUND: The genetic mechanisms underlying interindividual blood pressure variation reflect the complex interplay of both genetic and environmental variables. The current standard statistical methods for detecting genes involved in the regulation mechanisms of complex traits are based on univariate analysis. Few studies have focused on the search for and understanding of quantitative trait loci responsible for gene x environmental interactions or multiple trait analysis. Composite interval mapping has been extended to multiple traits and may be an interesting approach to such a problem. METHODS: We used multiple-trait analysis for quantitative trait locus mapping of loci having different effects on systolic blood pressure with NaCl exposure. Animals studied were 188 rats, the progenies of an F2 rat intercross between the hypertensive and normotensive strain, genotyped in 179 polymorphic markers across the rat genome. To accommodate the correlational structure from measurements taken in the same animals, we applied univariate and multivariate strategies for analyzing the data. RESULTS: We detected a new quantitative train locus on a region close to marker R589 in chromosome 5 of the rat genome, not previously identified through serial analysis of individual traits. In addition, we were able to justify analytically the parametric restrictions in terms of regression coefficients responsible for the gain in precision with the adopted analytical approach. CONCLUSION: Future work should focus on fine mapping and the identification of the causative variant responsible for this quantitative trait locus signal. The multivariable strategy might be valuable in the study of genetic determinants of interindividual variation of antihypertensive drug effectiveness.

Animals↗
PubMed2000

Process-based models for forest ecosystem management: current state of the art and challenges for practical implementation.

Recent progress toward the application of process-based models in forestmanagement includes the development of evaluation and parameter estimation methods suitable for models with causal structure, and the accumulation of data that can be used in model evaluation. The current state of the art of process modeling is discussed in the context of forest ecosystem management. We argue that the carbon balance approach is readily applicable for projecting forest yield and productivity, and review several carbon balance models for estimating stand productivity and individual tree growth and competition. We propose that to develop operational models, it is necessary to accept that all models may have both empirical and causal components at the system level. We present examples of hybrid carbon balance models and consider issues that currently require incorporation of empirical information at the system level. We review model calibration and validation methods that take account of the hybrid character of models. The operational implementation of process-based models to practical forest management is discussed. Methods of decision-making in forest management are gradually moving toward a more general, analytical approach, and it seems likely that models that include some process-oriented components will soon be used in forestry enterprises. This development is likely to run parallel with the further development of ecophysiologically based models.

Journal Article↗
PubMed2005

Walking and Non-HDL-C in adults: a meta-analysis of randomized controlled trials.

An elevated level of non-high-density lipoprotein cholesterol (non-HDL-C) is a major risk factor for cardiovascular disease. The purpose of this study was to use the meta-analytic approach to examine the effects of walking on non-HDL-C in adults. Twenty-two randomized controlled trials representing 30 outcomes from 948 subjects (573 exercise, 375 control) met our inclusion criteria. Across all designs and categories, random effects modeling resulted in a significantly greater decrease in the walking group when compared with the control group of approximately 4% for non-HDL-C (+/- standard error of the mean, -5.6+/-1.8 mg/dL, 95% confidence interval, -8.8 to -2.4 mg/dL). Meta-regression showed a statistically significant association between changes in non-HDL-C and the year of publication, with greater reductions associated with more recent publication year (R2 = 0.23, p = 0.005). The results of this meta-analytic review suggest that walking reduces non-HDL-C in adult humans.

Adult↗
PubMedDate not supplied

Classifying medical devices according to their maintenance sensitivity: a practical, risk-based approach to PM program management.

Many medical equipment items need periodic attention to ensure that they continue to operate properly and safely; and most inspecting agencies require healthcare facilities to have a competent equipment maintenance program that is focused on the most critical of those devices. There is however a long-standing lack of consensus on how best to determine which devices should be included in this critical device category, and which can reasonably be excluded. A new methodology is proposed for establishing a logical, fact-based framework for determining which devices should be included. It is based in part on a new FDA-sanctioned definition of what an appropriate regimen of planned maintenance activities for a medical device should include. This new definition addresses the medical device users' concerns about periodic performance verification and safety testing as well as detecting and correcting the wear or progressive deterioration of any non-durable parts, which is the primary focus of the conventional preventive maintenance programs found in less critical industries. The analytical approach proposed utilizes technical information that is either already available or which can be easily developed. It characterizes each different device by means of a 3-letter maintenance sensitivity profile that can be used to analyze the effectiveness of the maintenance procedures as well as quantify the device's sensitivity to planned maintenance. A collaborative effort to assemble and organize this data would provide the industry with a sound, logical platform for narrowing the scope of most PM programs and allow us to redirect a significant amount of scarce technical manpower into more productive activities such as device user training.

Equipment and Supplies↗
PubMed1999

Simulation for internal energy deposition in sustained off-resonance irradiation collisional activation using a monte carlo method

This paper proposes a novel computational approach employing a Monte Carlo method, aimed at an improved understanding of the dynamics and energetics of activated ions in sustained off-resonance irradiation collisionally activated dissociation (SORI-CAD) experimental events of Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS). In SORI-CAD events, internal energies of activated ions are complicatedly associated with their motion undergoing off-resonance excitation (i.e. alternate accelerations and decelerations) and inherently stochastic ion-neutral collisions. Several types of pseudo-random generators were adapted to probability density functions (PDFs) which characterize the ion-neutral collision process. Simulated ion trajectories involve the realistic feature of pressurized SORI-CAD events, such as a collisional damping and those which have not been illustrated in conventional analytical approaches. The proposed method can simulate the time-varying translational and internal energies of activated ions. The present result suggests that the internal energy of a SORI-activated ion should be inversely proportional to the cube of the SORI excitation frequency offset. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2006

Identification of base pairs in single-nucleotide polymorphisms by MutS protein-mediated capillary electrophoresis.

Single-nucleotide polymorphisms (SNPs) are widespread genomic variations, which are associated with serious health disorders and drug resistance. Multiple clinical applications and studies of global population genetics require fast and informative analysis of SNPs. Most of conventional methods sense the presence of the SNP but cannot identify the base pair in it. Here we report simple identification of base pairs in SNPs without DNA sequencing. Our approach is based on the unique ability of MutS protein to bind different single-nucleotide mismatches in DNA with different affinities. Conceptually, the DNA in question is mixed with reference DNA, melted, and reannealed. If the DNA in question has an SNP, the products of reannealing will have two different single-nucleotide mismatches, which provide a base-pair-specific signature of the SNP. The products of reannealing are mixed with MutS, equilibrated, and separated by equilibrium capillary electrophoresis of equilibrium mixtures with MutS in the run buffer. The pattern of migration times of DNAs with mismatches is used for unequivocal identification of the base pair in the SNP. In addition to its ability to identify base pairs in SNPs, the new analytical approach is fast, simple, highly sensitive, and requires no quantitation. It will find applications in studies of heterogeneity of base pairs in known SNPs in large human populations.

Base Pairing↗
PubMed2005

Skin infection, housing and social circumstances in children living in remote Indigenous communities: testing conceptual and methodological approaches.

BACKGROUND: Poor housing conditions in remote Indigenous communities in Australia are a major underlying factor in poor child health, including high rates of skin infections. The aim of this study is to test approaches to data collection, analysis and feedback for a follow-up study of the impact of housing conditions on child health. METHODS: Participation was negotiated in three communities with community councils and individual participants. Data were collected by survey of dwelling condition, interviews, and audit health centre records of children aged under seven years. Community feedback comprised immediate report of items requiring urgent repair followed by a summary descriptive report. Multivariate models were developed to calculate adjusted incidence rate ratios (IRR) for skin infections and their association with aspects of household infrastructure. RESULTS: There was a high level of participation in all communities. Health centre records were inadequate for audit in one community. The records of 138 children were available for development of multivariate analytic models. Rates of skin infection in dwellings that lacked functioning facilities for removing faeces or which had concrete floors may be up to twice as high as for other dwellings, and the latter association appears to be exacerbated by crowding. Younger children living in older dwellings may also be at approximately two-fold higher risk. A number of socioeconomic and socio-demographic variables also appear to be directly associated with high rates of skin infections. CONCLUSION: The methods used in the pilot study were generally feasible, and the analytic approach provides meaningful results. The study provides some evidence that new and modern housing is contributing to a reduction in skin infections in Aboriginal children in remote communities, particularly when this housing leads to a reduction in crowding and the effective removal of human waste.

Australia↗
PubMed1991

Biochemical diagnosis of systemic mast cell disorders.

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocyte activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.

Flushing↗
PubMed1991

Biochemical diagnosis of systemic mast cell disorders.

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocytes activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.

Humans↗
PubMed2006

Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals.

BACKGROUND: Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series. METHODS: Three methods were considered for the analyses of the cohort data: Poisson regression approach, case-crossover analyses and extended Cox regression analyses. The major challenge of these analyses is to appropriately consider changes within the cohort over time due to changes in the underlying risk following a myocardial infarction, slow time trends in risk factors within the population, dynamic cohort size and seasonal variation. RESULTS: Poisson regression analyses, case-crossover analyses and Extended Cox regression analyses gave similar results. Application of smoothing methods showed the capability to adequately model the complex time trends. CONCLUSION: From a practical point of view, Poisson regression analyses are less time-consuming, and therefore might be used for confounder selection and most of the analyses. However, replication of the results with Cox models is desirable to assure that the results are independent of the analytical approach used. In addition, extended Cox regression analyses would allow a joint estimation of long-term and short-term health effects of time-varying exposures.

Journal Article↗
PubMed2005

Determination of aromatic hydrotropic drugs in pharmaceutical preparations by the surfactant-binding degree method.

An aggregation parameter-based analytical approach, the surfactant-dye binding degree (SDBD) method, was used, for the first time, to determine aromatic hydrotropic compounds. The anionic dye Coomassie Brilliant Blue G (CBBG) was used as inductor of didodecyldimethylammonium bromide (DDABr) aggregates, whose formation was monitored from changes in the spectral features of the dye. Interactions between hydrotrope and DDABr molecules resulted in a decrease of the degree of binding of the cationic surfactant to CBBG, which was proportional to the concentration of hydrotrope in the aqueous solution. The CBBG-DDABr-hydrotrope chemical system was found to fit to the mathematical expression previously derived for the determination of amphiphilic compounds. The hydrotrope-surfactant bond strength determined the sensitivity achieved for the determination of hydrotropic compounds, which was highly dependent on the molecular structure of the analyte. The high precision (the relative standard deviation for 7 mg l(-1) of salicylic acid was 0.8%), rapidity (measurements were performed in a few minutes) and low cost (in both instrumentation and reactants) of the proposed method, made it especially suitable for quality control. The practical analytical applicability of the SDBD method for the control of hydrotropic drugs in pharmaceutical preparations was demonstrated by quantifying salicylic acid and acetyl salicylic acid in liquid (solutions) and solid (tablets, granulates, unguents, gels and creams) samples, which were directly analyzed after dissolution of the samples.

Chemistry, Pharmaceutical↗
PubMed1997

Dynamic resistance exercise and resting blood pressure in adults: a meta-analysis.

With the use of the meta-analytic approach, the purpose of this study was to examine the effects of dynamic resistance exercise, i.e., weight training, on resting systolic and diastolic blood pressure in adults. A total of nine studies consisting of 259 subjects (144 exercise, 115 control) and 18 groups (9 exercise, 9 control) were included in this analysis. With the use of the bootstrap technique (10,000 samples), significant treatment effect (delta 3) reductions were found across all designs and categories for both systolic and diastolic blood pressure [systolic, mean +/- SD = -4.55 +/- 1.75 mmHg, 95% confidence interval (CI) = -1.56 to -8.56; diastolic, mean +/- SD = -3.79 + 1.12 mmHg, 95% confidence interval CI = -1.89 to -6.33]. Delta 3 changes corresponded with relative decreases of approximately 3 and 4% in resting systolic and diastolic blood pressure, respectively. In conclusion, meta-analytic review of included studies suggests that dynamic resistance exercise reduces resting systolic and diastolic blood pressure in adults. However, it is premature to form strong conclusions regarding the effects of dynamic resistance exercise on resting blood pressure. A need exists for additional, well-designed studies on this topic before a recommendation can be made regarding the efficacy of dynamic resistance exercise as a nonpharmacological therapy for reducing resting blood pressure in adults, especially in hypertensive adults.

Adolescent↗
PubMed1993

Hormone replacement therapy and breast cancer mortality in Swedish women: results after adjustment for 'healthy drug-user' effect.

No change of breast cancer mortality has been reported previously after long-term hormone replacement therapy. A conceivable explanation for the apparent discrepancy between incidence and mortality may be selection bias due to lower prevalence of breast cancer in women who receive replacement hormones, compared with nonexposed women. We used a new approach to correct for bias due to this 'healthy drug-user effect,' by adjusting the external, population-based, mortality rates for such cases prevalent during the recruitment period of our cohort. In this cohort of some 23,000 Swedish women, who were prescribed various hormone replacement regimens, breast cancer mortality was analyzed after follow-up to 12 years. External analyses revealed overall standardized mortality ratios for breast cancer rising from 0.71 to 0.81, but not significantly different from unity, after adjustment procedures. In multivariate regression models, excluding prevalent cases in the cohort, women prescribed estradiol, conjugated estrogens, or an estrogen-progestin combination were not at a higher risk relative to those given other and weak estrogens, relative risks being 0.81 and 0.68, respectively. On the basis of the present analytical approach, we conclude that breast cancer mortality does not appear to be changed overall or in subgroups, despite increased incidence.

Aged↗
PubMed2004

A high-throughput approach for subcellular proteome: identification of rat liver proteins using subcellular fractionation coupled with two-dimensional liquid chromatography tandem mass spectrometry and bioinformatic analysis.

Four fractions from rat liver (a crude mitochondria (CM) and cytosol (C) fraction obtained with differential centrifugation, a purified mitochondrial (PM) fraction obtained with nycodenz density gradient centrifugation, and a total liver (TL) fraction) were analyzed with two-dimensional liquid chromatography tandem mass spectrometry analysis. A total of 564 rat proteins were identified and were bioinformatically annotated according to their physicochemical characteristics and functions. While most extreme alkaline ribosomal proteins were identified in the TL fraction, the C fraction mainly included neutral enzymes and the PM fraction enriched alkaline proteins and proteins with electron transfer activity or oxygen binding activity. Such characteristics were more apparent in proteins identified only in the TL, C, or PM fraction. The Swiss-Prot annotation and the bioinformatic prediction results proved that the C and PM fractions had enriched cytoplasmic or mitochondrial proteins, respectively. Combination usage of subcellular fractionation with two-dimensional liquid chromatography tandem mass spectrometry was proved to be a high-throughput, sensitive, and effective analytical approach for subcellular proteomics research. Using such a strategy, we have constructed the largest proteome database to date for rat liver (564 rat proteins) and its cytosol (222 rat proteins) and mitochondrial fractions (227 rat proteins). Moreover, the 352 proteins with Swiss-Prot subcellular location annotation in the 564 identified proteins were used as an actual subcellular proteome dataset to evaluate the widely used bioinformatics tools such as PSORT, TargetP, TMHMM, and GRAVY.

Animals↗