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PubMed2006

In pursuit of cumulative knowledge in health communication: the role of meta-analysis.

A major goal in health communication and related disciplines is the building of cumulative knowledge across numerous lines of inquiry. Traditionally, attempts to synthesize research and build knowledge have been achieved through narrative or integrative research reviews. However, the advent of meta-analysis in the late 1970s gave researchers a more sophisticated approach to synthesizing quantitative research literatures. This article (a) provides an overview of the meta-analytic approach, (b) discusses the historical context of meta-analysis, (c) examines the role that meta-analysis has played in the synthesis of health communication research, and (d) suggests future applications of the technique within health communication. It appears that meta-analysis has only recently been applied to the health communication field in a substantive way, and that its potential for moving the field forward has thus only begun to be realized.

Communication↗

PubMed2000

Meta-analysis: methods, strengths, and weaknesses.

Meta-analysis is a systematic, quantitative approach to the combination of data from several clinical trials that address the same question. This analytic approach can help resolve questions that remain unclear from the results of individual trials. Meta-analysis is of particular interest in oncology because of the small differences in efficacy between therapeutic alternatives. The large number of patients included in meta-analyses permit small to moderate benefits of a treatment to be reliably detected and larger treatment benefits to be quantified more accurately. Despite these apparent benefits, the use of meta-analysis has met with a great deal of resistance and has generated much controversy in clinical journals. After a brief description of the basic methods of conducting meta-analyses, this article will explore both their advantages and disadvantages.

Bias↗

PubMed2004

A multilevel approach to youth physical activity research.

Social environment factors are hypothesized to interact with individual-level factors to influence youth physical activity. Multilevel analytic approaches are ideal for examining the influence of the social environment on youth physical activity as they allow examination of research questions across multiple contexts and levels ( e.g., individual, family, and neighborhood levels).

Adolescent↗

PubMedDate not supplied

An economic approach to clinical trial design and research priority-setting.

Whilst significant advances have been made in persuading clinical researchers of the value of conducting economic evaluation alongside clinical trials, a number of problems remain. The most fundamental is the fact that economic principles are almost entirely ignored in the traditional approach to trial design. For example, in the selection of an optimal sample size no consideration is given to the marginal costs or benefits of sample information. In the traditional approach this can lead to either unbounded or arbitrary sample sizes. This paper presents a decision-analytic approach to trial design which takes explicit account of the costs of sampling, the benefits of sample information and the decision rules of cost-effectiveness analysis. It also provides a consistent framework for setting priorities in research funding and establishes a set of screens (or hurdles) to evaluate the potential cost-effectiveness of research proposals. The framework permits research priority setting based explicitly on the budget constraint faced by clinical practitioners and on the information available prior to prospective research. It demonstrates the link between the value of clinical research and the budgetary restrictions on service provision, and it provides practical tools to establish the optimal allocation of resources between areas of clinical research or between service provision and research.

Bayes Theorem↗

PubMed1989

[Epidemiology and heterogeny].

The innovation of epidemiology plays a crucial role in the development of the health sciences. The authors emphasize the importance of epistemological analysis related to scientific and technical production. They focus on the theoretical and methodological contributions of the principal Latin American groups in the field of epidemiology, stating their main accomplishments, issues and potentials. When reviewing those conceptual and practical innovations, the authors analyse the effects of broader historical conditions on scientific work. To them, Latin American contemporary innovative epidemiological research and production have developed clearly differentiated principles, methods and technical projections which have led to a movement of critical or 'social' epidemiology. The functionalist approach of conventional epidemiology, characterized by an empiricist viewpoint, is being overcome by a more rigorous and analytical approach. This new epidemiological approach, in which the authors as members of CEAS (Health Research and Advisory Center) are working, has selectively incorporated some of the technical instruments of conventional epidemiology, subordinating them to a different theoretical and logical paradigm. The new framework of this group explains the need to consider the people's objective situation and necessities, when constructing scientific interpretations and planning technical action. In order to accomplish this goal, epidemiological reasoning has to reflect the unity of external epidemiological facts and associations, the so-called phenomenological aspect of health, with the underlying determinants and conditioning processes or internal relations, which are the essence of the health-disease production and distribution process. Epidemiological analysis is considered not only as a problem of empirical observation but as a process of theoretical construction, in which there is a dynamic fusion of deductive and inductive reasoning.(ABSTRACT TRUNCATED AT 250 WORDS)

Delivery of Health Care↗

PubMed2004

A technique for standardized central analysis of 6-(18)F-fluoro-L-DOPA PET data from a multicenter study.

UNLABELLED: We have recently completed a large 6-(18)F-fluoro-L-DOPA ((18)F-DOPA) PET study comparing rates of loss of dopamine terminal function in Parkinson's disease (PD) patients taking either the dopamine agonist ropinirole or L-DOPA. This trial involved a "distributed acquisition/centralized analysis" method, in which (18)F-DOPA images were acquired at 6 different PET centers around the world and then analyzed at a single site. To our knowledge, this is the first time such a centralized approach has been employed with (18)F-DOPA PET and this descriptive basic science article outlines the methods used. METHODS: One hundred eighty-six PD patients were randomized (1:1) to ropinirole or L-DOPA therapy, and (18)F-DOPA PET was performed at baseline and again at 2 y. The primary outcome measure was the percentage change in putamen (18)F-DOPA influx rate constant (K(i)) from Patlak graphical analysis. Dynamic images were acquired and reconstructed using each center's individual protocols before being transferred to the site performing the central analysis. Once there, individual parametric K(i) images were created using a single analysis program without file formats being transformed from the original. Parametric images were then normalized to standard space and K(i) values extracted with a region of interest analysis. Significant K(i) changes were also localized at a voxel level with statistical parametric mapping. These processes required numerous checks to ensure the integrity of each dataset. RESULTS: Three hundred twenty-five (170 baseline, 155 follow-up) dynamic PET datasets were acquired, of which 12 were considered uninterpretable due to missing time frames, radiopharmaceutical problems, lack of measured attenuation correction, or excessive head movement. In those datasets suitable for central analysis, after quality control and spatial normalization of the images had been applied, putamen (18)F-DOPA signal decline was found to be significantly (one third) slower in the ropinirole group compared with that of the L-DOPA group. CONCLUSION: Paired (18)F-DOPA-PET images acquired from multiple sites can be successfully analyzed centrally to assess the efficacy of potential disease-modifying therapies in PD. However, numerous options must be considered and data checks put in place before adopting such an approach. Centralized analysis offers the potential for improved detection of outcomes due to the standardization of the analytic approach and allows the analysis of large numbers of PET studies.

Algorithms↗

PubMed1999

Efficiency of two different nine-loci short tandem repeat systems for DNA typing purposes.

BACKGROUND: Genotyping based on short tandem repeat (STR) regions is widely used in human identification and parentage testing, in gene mapping studies, and as an approach to studies on the etiopathogenesis and diagnosis of hereditary diseases. We wished to study a new analytical approach that uses capillary electrophoresis and multicolor fluorescence in place of slab gel electrophoresis. METHODS: We evaluated the efficiency for parentage and forensic purposes of the AmpFLSTR Profiler PlusTM typing kit that is used with the ABI Prism 310 Genetic Analyzer (System-2 STR), and that of a widely used panel of nine STRs analyzed with conventional slab-gel electrophoresis followed by radioactive detection (System-1 STR). System-2 STR, based on automated capillary electrophoresis and automated sizing of the alleles by Genotyper 2.0 software, was used to determine the allele frequency of the nine loci in 157 Caucasian subjects from southern Italy. On the basis of the data obtained, we submitted 40 trios to parentage testing. RESULTS: A higher median probability of paternity attribution and power of exclusion were obtained with System-2 STR vs System-1 STR: respectively, 99.99% and 99.95% (P <0.05) for attribution; and five and four excluding loci (P <0.05) for exclusion. The most informative and highly discriminating loci were D18S51, D21S11, and FGA. The combined probability of matching-by-chance for all nine STRs was 1.36 x 10(-12) for System-2 compared with 1.11 x 10(-7) obtained with the other system. The internal standard and allelic ladder of the System-2 STR facilitated accurate and precise genotyping; furthermore, System-2 STR and was faster than the conventional System-1 STR. CONCLUSIONS: The System-2 STR allows rapid testing with higher probabilities of attribution and a higher power of exclusion than with the comparison method with slab-gel electrophoresis.

Alleles↗

PubMed2006

Environmental proteomics and metallomics.

Monitoring environmental pollution using biomarkers requires detailed knowledge about the markers, and many only allow a partial assessment of pollution. New proteomic methods (environmental proteomics) can identify proteins that, after validation, might be useful as alternative biomarkers, although this approach also has its limitations, derived mainly from their application to non-model organisms. Initial studies using environmental proteomics were carried out in animals exposed to model pollutants, and led to the concept of protein expression signatures. Experiments have been carried out in model organisms (yeast, Arabidopsis, rat cells, or mice) exposed to model contaminants. Over the last few years, proteomics has been applied to organisms from ecosystems with different pollution levels, forming the basis of an environmental branch in proteomics. Another focus is connected with the presence of metals bound to biomolecules, which adds an additional dimension to metal-biomolecule and metalloprotein characterization - the field of metallomics. The metallomic approach considers the metallome: a whole individual metal or metalloid species within a cell or tissue. A metallomic analytical approach (MAA) is proposed as a new tool to study and identify metalloproteins.

Animals↗

PubMed1998

Bronchioloalveolar adenocarcinoma of lung: monoclonal origin for multifocal disease.

In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-ras mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-ras mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1992

Dual Analyte immunoassay--a new approach to neural tube defect and Down's syndrome screening.

A microtiter plate based Dual Analyte enzyme-immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and Free-beta human chorionic gonadotrophin (hCG) was evaluated. This rapid assay, which has application in both Neural Tube Defect screening and Down's screening, shows good precision with between assay coefficients of variation between 5 and 7.5% for AFP and 3.7 to 5.8% for Free-beta(hCG). Correlation with single analyte procedures is good, with correlation coefficients being greater than 0.91 in both cases. Clinical discrimination in detecting both types of abnormalities is not compromised by this new simultaneous Dual Analyte assay. We conclude that the Dual Analyte approach, which combines analytes achieving the highest known detection efficiency, will bring about improvements in the efficiency of screening, reduce costs and improve report turnaround, all leading to better quality of patient care.

Chorionic Gonadotropin↗

PubMed2005

Comparison of a spatial approach with the multilevel approach for investigating place effects on health: the example of healthcare utilisation in France.

STUDY OBJECTIVE: Most studies of place effects on health have followed the multilevel analytical approach that investigates geographical variations of health phenomena by fragmenting space into arbitrary areas. This study examined whether analysing geographical variations across continuous space with spatial modelling techniques and contextual indicators that capture space as a continuous dimension surrounding individual residences provided more relevant information on the spatial distribution of outcomes. Healthcare utilisation in France was taken as an illustrative example in comparing the spatial approach with the multilevel approach. DESIGN: Multilevel and spatial analyses of cross sectional data. PARTICIPANTS: 10,955 beneficiaries of the three principal national health insurance funds, surveyed in 1998 and 2000 on continental France. MAIN RESULTS: Multilevel models showed significant geographical variations in healthcare utilisation. However, the Moran's I statistic showed spatial autocorrelation unaccounted for by multilevel models. Modelling the correlation between people as a decreasing function of the spatial distance between them, spatial mixed models gave information not only on the magnitude, but also on the scale of spatial variations, and provided more accurate standard errors for risk factors effects. The socioeconomic level of the residential context and the supply of physicians were independently associated with healthcare utilisation. Place indicators better explained spatial variations in healthcare utilisation when measured across continuous space, rather than within administrative areas. CONCLUSIONS: The kind of conceptualization of space during analysis influences the understanding of place effects on health. In many contextual studies, viewing space as a continuum may yield more relevant information on the spatial distribution of outcomes.

Adult↗

PubMed2002

Comparative cardiovascular development: improving the conceptual framework.

Immature vertebrates-either as an embryo in an egg, as free-living larva, or as an in utero fetus, are clearly not just small versions of adults. Their cardiovascular physiology (and doubtlessly other aspects of physiology) differs from that of adults both qualitatively and quantitatively. Yet, comparative cardiovascular physiologists have been relatively conservative in constructing a new (or at least modified) conceptual framework for the understanding of developmental cardiovascular physiology. We recommend that this framework rely less on the established cardiovascular truisms for adult cardiovascular physiology that are proving to be less useful and in instances even inaccurate for interpreting development of the heart and vasculature. We have suggested that three methodologies in particular be incorporated to a greater extent in studies of comparative cardiovascular development: (a) emphasis on multivariate approaches; (b) differentiation between absolute (extrinsic) and relative (intrinsic) time for development, and; (c) employment of time lines for both intra- and interspecific comparisons of the ontogeny of cardiovascular processes. While certainly none of these approaches are novel and others have previously dwelt at length on their importance in other contexts, we feel that the emerging framework for investigating cardiovascular physiological development would benefit from incorporating these and other approaches into experimental design as well as data analysis. Failing to do so results in a heavy dependence on analytical approaches typically used for adults, and thus under-appreciates the novelty and complexity of the developing vertebrate cardiovascular system.

Animals↗

PubMed2006

Numerical and analytical studies of the electrical conductivity of a concentrated colloidal suspension.

In the past few years, different models and analytical approximations have been developed facing the problem of the electrical conductivity of a concentrated colloidal suspension, according to the cell-model concept. Most of them make use of the Kuwabara cell model to account for hydrodynamic particle-particle interactions, but they differ in the choice of electrostatic boundary conditions at the outer surface of the cell. Most analytical and numerical studies have been developed using two different sets of boundary conditions of the Neumann or Dirichlet type for the electrical potential, ionic concentrations or electrochemical potentials at that outer surface. In this contribution, we study and compare numerical conductivity predictions with results obtained using different analytical formulas valid for arbitrary zeta potentials and thin double layers for each of the two common sets of boundary conditions referred to above. The conductivity will be analyzed as a function of particle volume fraction, phi, zeta potential, zeta, and electrokinetic radius, kappaa (kappa(-1) is the double layer thickness, and a is the radius of the particle). A comparison with some experimental conductivity results in the literature is also given. We demonstrate in this work that the two analytical conductivity formulas, which are mainly based on Neumann- and Dirichlet-type boundary conditions for the electrochemical potential, predict values of the conductivity very close to their corresponding numerical results for the same boundary conditions, whatever the suspension or solution parameters, under the assumption of thin double layers where these approximations are valid. Furthermore, both analytical conductivity equations fulfill the Maxwell limit for uncharged nonconductive spheres, which coincides with the limit kappaa --> infinity. However, some experimental data will show that the Neumann, either numerical or analytical, approach is unable to make predictions in agreement with experiments, unlike the Dirichlet approach which correctly predicts the experimental conductivity results. In consequence, a deeper study has been performed with numerical and analytical predictions based on Dirichlet-type boundary conditions.

Journal Article↗

PubMed2006

Regulation of gene expression in the mammalian eye and its relevance to eye disease.

We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F(2) rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta2 associated with a decreased expression level of the gene encoding short-wavelength sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet-Biedl syndrome. These data and analytical approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease.

Analysis of Variance↗

PubMed2006

Chirality dependence of carbon single-walled nanotube material properties: axial coefficient of thermal expansion.

Carbon nanotubes are one of the best candidates for applications where structural, thermal, and chemical stabilities are of great importance. Despite the fact that significant efforts have been devoted to study properties and behavior of the carbon nanotubes in recent years, there have not been sufficient results available on their thermoelastic properties. This paper investigates the chirality dependence of coefficient of thermal expansion of carbon single-walled nanotubes both analytically and numerically. The analytical approach in characterizing the chirality dependence of the coefficient of thermal expansion uses an asymptotic homogenization method. A second analytical interpretation follows a free-expansion strain method based on basic principles of thermoelasticity. The derived formulae make it easy to understand the dependencies of the nanotube thermoelastic properties on its geometrical parameters. The results from these analytical studies were verified using a finite element method. All three independent studies consistently demonstrate that the coefficient of thermal expansion of carbon single-walled nanotubes is independent of their chirality.

Anisotropy↗

PubMed2004

Economic endpoints in clinical trials.

Healthcare decision makers are increasingly requesting information on the cost and cost-effectiveness of new medicines at the time of product launch. In order to provide this information, data on healthcare resource utilization and, in some cases, costs, may be collected in clinical trials. In this paper, we discuss some of the issues statisticians need to address when it is appropriate to include these economic endpoints in the trial. Several design issues are discussed, including the alternative types of and methods for collecting economic endpoint data, sample size and generalizability. Alternative approaches in the analysis of resource utilization, cost and cost-effectiveness are also presented. Finally, several of the analytic approaches are applied to actual data from a clinical trial.

Clinical Trials as Topic↗

PubMed2000

A one-dimensional fluid dynamic model of the systemic arteries.

The systemic arteries can be modeled as a bifurcating tree of compliant tapering vessels while blood flow and pressure can be predicted by solving Navier-Stokes equations for each of the branches. If all branches are included the computational cost will become prohibitively large. Therefore, the tree must be truncated after a limited number of generations and a suitable outflow boundary condition must be applied. To this end we propose a structured tree in which the root impedance is calculated using a semi-analytical approach. In the structured tree the fluid dynamic equations are linearized giving a wave equation, which can be solved analytically for each vessel. This provides a dynamical boundary condition based on physiological principles which is computationally feasible. It exhibits the actual phase lag between flow and pressure as well as accommodating the wave propagation effects for the entire systemic arterial tree. Finally, the model has been compared with a standard and well established model, where outflow at the terminals are determined by attaching a Windkessel type boundary condition.

Arteries↗

PubMed1999

Potential for bias in estimating human fecundability parameters: a comparison of statistical models.

Fecundability studies, where couples attempting pregnancy subject to 'failure' (conception) one time in each menstrual cycle, present a natural discrete failure-time scenario. Because the biologic capacity to conceive varies among couples in the population, a complication arises in choosing a method of analysis, related to the fact that the maximum follow-up time can vary from study to study, and follow-up time could potentially have different effects on parameters based on different approaches to modelling. Traditional development in fertility studies has been based on an implicit assumption that binary outcomes for different menstrual cycles are mutually independent. We contrast traditional models to a random effects model where cycle viability is modelled as subject-specific. We clarify the interpretations for different parameters from different models. We show that the traditional approach yields some regression parameters that depend on follow-up time, limiting the generalizability of inferences based on this analytic approach. By contrast, the subject-specific model consistently estimates parameters of interest, if the underlying distribution is properly specified. Data from a fecundability study carried out in North Carolina serves to illustrate these points.

Bias↗