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PubMed1999

Interaction between impaired and unimpaired speakers: inter-subjectivity and the interplay of culturally shared and situation specific knowledge.

The part played by culturally shared knowledge in interaction is generally recognised. However, the details of how it may be manifested in interaction are largely undocumented. This study explores this issue in the context of interactions between impaired and unimpaired speakers, using a conversation analytic approach in combination with a communication task commonly employed in experimental social psychology. Three exemplary cases are analysed. Results show that when the task interaction is co-constructed, the interaction is collaboratively enacted, participants' actions are in alignment, and the task outcome is relatively accurate. When the unimpaired speaker proceeds on the basis of culturally shared knowledge, and thereby 'unilaterally' manages the interaction, two courses of action are available to the impaired speaker. The impaired speaker may make attempts to provide situation specific details. In this case, because each participant is drawing on different resources to construct the interaction, their actions are out of alignment, and the task outcome is less accurate. Alternatively, the impaired speaker may concur with the culturally shared knowledge drawn on by the unimpaired speaker, in which case the participants' actions are in alignment, but the task outcome is highly inaccurate. The authors conclude that by combining a conversation analytic approach with a communication task which reflects participants' everyday experiences, orientations to different interaction resources can be drawn out. This can have relevance for, and help to elicit, practices in everyday interaction.

Adult↗
PubMed2005

Analyzing patterns of staining in immunohistochemical studies: application to a study of prostate cancer recurrence.

BACKGROUND: Immunohistochemical studies use antibodies to stain tissues with the goal of quantifying protein expression. However, protein expression is often heterogeneous resulting in variable degrees and patterns of staining. This problem is particularly acute in prostate cancer, where tumors are infiltrative and heterogeneous in nature. In this article, we introduce analytic approaches that explicitly consider both the frequency and intensity of tissue staining. METHODS: Compositional data analysis is a technique used to analyze vectors of unit-sum proportions, such as those obtained from soil sample studies or species abundance surveys. We summarized specimen staining patterns by the proportion of cells staining at mild, moderate, and intense levels and used compositional data analysis to summarize and compare the resulting staining profiles. RESULTS: In a study of Syndecan-1 staining patterns among 44 localized prostate cancer cases with Gleason score 7 disease, compositional data analysis did not detect a statistically significant difference between the staining patterns in recurrent (n = 22) versus nonrecurrent (n = 22) patients. Results indicated only modest increases in the proportion of cells staining at a moderate intensity in the recurrent group. In contrast, an analysis that compared quantitative scores across groups indicated a (borderline) significant increase in staining in the recurrent group (P = 0.05, t test). CONCLUSIONS: Compositional data analysis offers a novel analytic approach for immunohistochemical studies, providing greater insight into differences in staining patterns between groups, but possibly lower statistical power than existing, score-based methods. When appropriate, we recommend conducting a compositional data analysis in addition to a standard score-based analysis.

Biomarkers, Tumor↗
PubMed2001

High-performance liquid chromatography--ToxPrint: chromatographic analysis with a novel (geno)toxicity detection.

In order to aid the monitoring of the overall quality of (surface) waters a new analytical approach has been developed, combining on-line solid-phase extraction, HPLC separation and effect-related detection. Compounds present in surface water or wastewater samples are extracted on-line with Oasis [poly(divinylbenzene-co-N-vinylpyrrolidone)] material and directly fractionated by reversed-phase HPLC. The eluent of the total chromatogram is collected on a microtitre plate in fractions of 1 min each. After evaporation and re-dissolvation in a suitable solvent, the (geno)toxicity of the individual fractions before and after enzymatic activation with S9, is determined with the umu test. In this way, harmful compounds can be detected and localized in the HPLC-diode array detection trace even without their identity and exact concentration being known at that moment. The method was developed using two test compounds, 4-nitroquinoline-N-oxide and 2-aminoanthracene. Compounds with mutagenic properties comparable to those of the test compounds can be detected from 0.1 microg/l, which is a concentration relevant for surface waters. The new analytical approach was successfully applied to various types of model samples, as well as real wastewater.

4-Nitroquinoline-1-oxide↗
PubMed2000

Multi-color analysis of monocyte and dendritic cell precursor heterogeneity in whole blood.

The coexpression analysis of the 55-kDa lipopolysaccharide receptor (CD14) and the Fc gamma-receptor III (CD16) reveals a broad heterogeneity of blood monocytes which in our previous work could be divided into five subpopulations based on correlated differences in expression of the pan-myeloid antigen CD33 and the adhesion antigens CD11a, CD11b and CD56. An even larger complexity of myeloid cells with antigen presenting capacity in peripheral blood is suggested by the description of small populations of immature and mature precursors of dendritic cells which rapidly develop potent costimulatory activity and a dendritic morphology in in vitro culture. The identity of the subsets of cells which have been described based on heterogeneous analytical approaches, however, remains unclear. The goal of this study, therefore, was the correlated analysis of monocyte subpopulations and dendritic cell precursors in a quantitative whole blood assay. This was achieved based on simultaneous expression analysis of the monocyte markers CD14 and CD16 with antigens such as CD33, HLA-DR, the integrin CD11c, and the interleukin-3 receptor alpha-chain (CD123) which in absence of lineage-related antigens have been used for description of dendritic cell precursors. The selected marker panel revealed identity of cells previously described as CD33bright CD14dim dendritic cell precursors with CD11c+lin-HLA-DR+ cells. Dendritic cell precursors considered to be less mature which have been alternatively described as CD33+ CD14dim CD16- cells or CD123hi dendritic cell precursors, however, were shown to differ in phenotype from each other with regard to expression density of CD33 and expression of CD14. In summary, our study revealed a complex heterogeneity of monocytes and dendritic cell precursors in peripheral blood and indicates that a direct comparison of the analytical approaches of different authors is needed to further clarify the ontogeny of human monocytes and dendritic cells.

Antigens, CD↗
PubMed2004

Database development in toxicogenomics: issues and efforts.

The marriage of toxicology and genomics has created not only opportunities but also novel informatics challenges. As with the larger field of gene expression analysis, toxicogenomics faces the problems of probe annotation and data comparison across different array platforms. Toxicogenomics studies are generally built on standard toxicology studies generating biological end point data, and as such, one goal of toxicogenomics is to detect relationships between changes in gene expression and in those biological parameters. These challenges are best addressed through data collection into a well-designed toxicogenomics database. A successful publicly accessible toxicogenomics database will serve as a repository for data sharing and as a resource for analysis, data mining, and discussion. It will offer a vehicle for harmonizing nomenclature and analytical approaches and serve as a reference for regulatory organizations to evaluate toxicogenomics data submitted as part of registrations. Such a database would capture the experimental context of in vivo studies with great fidelity such that the dynamics of the dose response could be probed statistically with confidence. This review presents the collaborative efforts between the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress, the International Life Sciences Institute Health and Environmental Science Institute, and the National Institute of Environmental Health Sciences National Center for Toxigenomics Chemical Effects in Biological Systems knowledge base. The goal of this collaboration is to establish public infrastructure on an international scale and examine other developments aimed at establishing toxicogenomics databases. In this review we discuss several issues common to such databases: the requirement for identifying minimal descriptors to represent the experiment, the demand for standardizing data storage and exchange formats, the challenge of creating standardized nomenclature and ontologies to describe biological data, the technical problems involved in data upload, the necessity of defining parameters that assess and record data quality, and the development of standardized analytical approaches.

Animals↗
PubMed2004

Current smoking among young adolescents: assessing school based contextual norms.

OBJECTIVE: To extend research on the relation of school based contextual norms to current smoking among adolescents by using three analytic techniques to test for contextual effects. It was hypothesised that significant contextual effects would be found in all three models, but that the strength of these effects would vary by the statistical rigor of the model. DESIGN: Three separate analytic approaches were conducted on baseline self report student survey data from a larger study to test the relation between school level perceived peer tobacco use and individual current smoking status. PARTICIPANTS: A representative sample of 5399 sixth through eighth grade students in 14 midwestern middle schools completed the survey. All enrolled sixth through eighth grade students were eligible to participate in the survey. The student participation rate was 91.4% for the entire sample, and did not differ significantly between the schools (range 82-100%). MAIN OUTCOME MEASURE: Thirty day cigarette smoking prevalence. RESULTS: A level 2 only model based on aggregated individual responses indicated that students in schools with higher average reported peer tobacco use were more likely to be current smokers than students in schools with lower average peer tobacco use. Using a level 1 only model based on individual responses indicated that the effect of school level perceived peer tobacco use on current smoking was significant when individual perceived peer tobacco use was excluded from the model but was non-significant when individual perceived peer tobacco use was added to the model. A multilevel model also indicated that the effect of school level perceived peer tobacco use on current smoking was not significant when individual perceived peer tobacco use was added to the model. CONCLUSION: The analytic approach used to examine contextual effects using individuals' reports of peer tobacco use norms that were aggregated to obtain a context measure of the school norms may produce statistical artefacts that distort the association of the school context in general, and peer tobacco use norms in particular, with increased risk for current smoking beyond the risk associated with individual factors.

Adolescent↗
PubMedDate not supplied

Drawdown and stream depletion produced by pumping in the vicinity of a partially penetrating stream.

Commonly used analytical approaches for estimation of pumping-induced drawdown and stream depletion are based on a series of idealistic assumptions about the stream-aquifer system. A new solution has been developed for estimation of drawdown and stream depletion under conditions that are more representative of those in natural systems (finite width stream of shallow penetration adjoining an aquifer of limited lateral extent). This solution shows that the conventional assumption of a fully penetrating stream will lead to a significant overestimation of stream depletion (> 100%) in many practical applications. The degree of overestimation will depend on the value of the stream leakance parameter and the distance from the pumping well to the stream. Although leakance will increase with stream width, a very wide stream will not necessarily be well represented by a model of a fully penetrating stream. The impact of lateral boundaries depends upon the distance from the pumping well to the stream and the stream leakance parameter. In most cases, aquifer width must be on the order of hundreds of stream widths before the assumption of a laterally infinite aquifer is appropriate for stream-depletion calculations. An important assumption underlying this solution is that stream-channel penetration is negligible relative to aquifer thickness. However, an approximate extension to the case of nonnegligible penetration provides reasonable results for the range of relative penetrations found in most natural systems (up to 85%). Since this solution allows consideration of a much wider range of conditions than existing analytical approaches, it could prove to be a valuable new tool for water management design and water rights adjudication purposes.

Conservation of Natural Resources↗
PubMed2005

Copper bioavailability in a coastal environment of Northern Chile: comparison of bioassay and analytical speciation approaches.

An integrated approach including chemical speciation analyses and microalgal bioassays was used to assess the impact of copper from copper mining on a coastal area in Northern Chile. Dissolved copper ranged from <1 microg l(-1) at reference sites to 48 microgl(-1) at sites close to the mine discharge. Dissolved copper at sites closest to the discharge always exceeded seawater complexing capacities determined by anodic stripping voltammetry (ASV), and consequently labile copper was always detected (1-37 microg l(-1)). Agreement between ASV-labile copper and copper retained by cation exchange (ALSA) columns was excellent. Measured labile copper also accurately predicted bioavailable copper determined by growth inhibition of Nitzschia closterium and enzyme inhibition in Dunaliella tertiolecta. Seawater from Caleta La Lancha had the highest dissolved and labile copper and was the most toxic to micro-algal growth and enzyme activity. Previous studies at this site confirmed it had the lowest level of biodiversity, suggesting that copper may have both direct and indirect effects on these communities.

Biological Assay↗
PubMed2002

On aerodynamic modelling of an insect-like flapping wing in hover for micro air vehicles.

This theoretical paper discusses recent advances in the fluid dynamics of insect and micro air vehicle (MAV) flight and considers theoretical analyses necessary for their future development. The main purpose is to propose a new conceptual framework and, within this framework, two analytic approaches to aerodynamic modelling of an insect-like flapping wing in hover in the context of MAVs. The motion involved is periodic and is composed of two half-cycles (downstroke and upstroke) which, in hover, are mirror images of each other. The downstroke begins with the wing in the uppermost and rearmost position and then sweeps forward while pitching up and plunging down. At the end of the half-cycle, the wing flips, so that the leading edge points backwards and the wing's lower surface becomes its upper side. The upstroke then follows by mirroring the downstroke kinematics and executing them in the opposite direction. Phenomenologically, the interpretation of the flow dynamics involved, and adopted here, is based on recent experimental evidence obtained by biologists from insect flight and related mechanical models. It is assumed that the flow is incompressible, has low Reynolds number and is laminar, and that two factors dominate: (i) forces generated by the bound leading-edge vortex, which models flow separation; and (ii) forces due to the attached part of the flow generated by the periodic pitching, plunging and sweeping. The first of these resembles the analogous phenomenon observed on sharp-edged delta wings and is treated as such. The second contribution is similar to the unsteady aerodynamics of attached flow on helicopter rotor blades and is interpreted accordingly. Theoretically, the fluid dynamic description is based on: (i) the superposition of the unsteady contributions of wing pitching, plunging and sweeping; and (ii) adding corrections due to the bound leading-edge vortex and wake distortion. Viscosity is accounted for indirectly by imposing the Kutta condition on the trailing edge and including the influence of the vortical structure on the leading edge. Mathematically, two analytic approaches are proposed. The first derives all the quantities of interest from the notion of circulation and leads to tractable integral equations. This is an application of the von Kármán-Sears unsteady wing theory and its nonlinear extensions due to McCune and Tavares; the latter can account for the bound leading-edge vortex and wake distortion. The second approach uses the velocity potential as the central concept and leads to relatively simple ordinary differential equations. It is a combination of two techniques: (i) unsteady aerodynamic modelling of attached flow on helicopter rotor blades; and (ii) Polhamus's leading-edge suction analogy. The first of these involves both frequency-domain (Theodorsen style) and time-domain (indicial) methods, including the effects of wing sweeping and returning wake. The second is a nonlinear correction accounting for the bound leading-edge vortex. Connections of the proposed framework with control engineering and aeroelasticity are pointed out.

Animals↗
PubMed2002

Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy.

OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified as responders (ITT/s=f); and 2) patients with a pVL below a given cut-off at week 48 whether they remained on initial assigned therapy or switched therapy were responders (ITT/s incl). In both analyses, patients with missing data at week 48 were classified as failures (i.e., non-responders). RESULTS: According to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT/s=f, and 41-72% according to ITT/s incl. Among those who discontinued the therapy to be evaluated in these two trials, 13-45% (cohort: 39-74%) subsequently experienced a virological response at week 48. The subsequent response rates were associated with the reason for discontinuation (toxicity versus confirmed virological failure: 63 vs 33%), varied largely across regimens and were not associated with the discontinuation rate. CONCLUSIONS: Discontinuation of follow-up at switch from the therapy to be evaluated remains common in antiretroviral treatment trials, but leads to an imprecise and incomplete assessment of the intrinsic effect of a given regimen. Complete follow-up of all patients should be encouraged strongly as this will allow for several complementary analytic approaches and a focus on optimal treatment strategies rather than specific regimens.

Antiretroviral Therapy, Highly Active↗
PubMed2006

A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending: Part II: Qualitative near-infrared models for prediction of blend homogeneity.

The successful implementation of near-infrared spectroscopy (NIRS) in process control of powder blending requires constructing an inclusive spectral database that reflects the anticipated voluntary or involuntary changes in processing conditions, thereby minimizing bias in prediction of blending behavior. In this study, experimental design was utilized as an efficient way of generating blend experiments conducted under varying processing conditions such as humidity, blender speed and component concentration. NIR spectral data, collected from different blending experiments, was used to build qualitative models for prediction of blend homogeneity. Two pattern recognition algorithms: Soft Independent Modeling of Class Analogies (SIMCA) and Principal Component Modified Bootstrap Error-adjusted Single-sample Technique (PC-MBEST) were evaluated for qualitative analysis of NIR blending data. Optimization of NIR models, for the two algorithms, was achieved by proper selection of spectral processing, and training set samples. The models developed were successful in predicting blend homogeneity of independent blend samples under different processing conditions.

Algorithms↗
PubMed1977

A factor analytic--genetic approach to the relation between obesity and behavior in mice.

Genetically heterogenous mice (N = 377) were reared on either high- or low-fat diets for the first 40 days of life. The mice were cross fostered to permit the separation of genetic and environmental effects in a sibling analysis. A total of 26 measures were taken on these mice, including oxygen consumption, activity, sucrose consumption, body weight changes when bitter or high-fat diets were given as the only food, and various morphological measures. A principal-factor analysis of these measures produced eight factors, most of which appeared to be "instrument" factors rather than general factors. Analyses of variance on the factor scores indicated that genetic influences contributed to five of the factors and sex contributed to three of the factors. However, none of the main effects of diet, gene by environment interactions, or sex by environment interactions were significant. Although obesity and behaviors were correlated, the magnitudes of the correlations were generally small.

Age Factors↗
PubMedDate not supplied

Analytical bayesian approach for assigning individuals to populations.

We propose a general formulation of the Bayesian method for assigning individuals to a population among a predetermined set of reference populations using molecular marker information. Compared to previously published methods, ours allows us to consider different types of prior information about allele frequencies by using a Dirichlet prior probability distribution. It also makes it possible to assign a set of individuals assumed to belong to the same population with increased accuracy using their pooled genotype data. The efficiency of the method is illustrated by application to a group of closely related coconut populations. An interesting feature of the Bayesian procedure is the way it handles imprecise information. With a poor or even incomplete dataset, assignment is still be possible and gives valid results: poor data quality is reflected in an ambiguous result rather than in a false conclusion.

Bayes Theorem↗
PubMed2026

Challenges for reproducibility in species delimitation.

Species richness is a foundational metric for comparing biodiversity among clades and regions in ecology, evolution, and conservation. As the biodiversity crisis accelerates, taxonomists face increasing pressure to delimit and name species rapidly, often relying on automated or semi-automated methods that prioritize speed over thoroughness. Yet the reproducibility of species delimitation (the degree to which independent experts reach consistent conclusions given the same evidence) remains largely unquantified, and its consequences for estimates of species richness have never been assessed at the scale of an entire fauna. This gap is consequential: if species delimitation is highly variable among practitioners, then published species counts may reflect the idiosyncrasies of individual taxonomists as much as the true biological structure of diversity within and among clades. Here we evaluate the precision, or reproducibility, of species delimitation in Neotropical freshwater fishes, the most species-rich continental vertebrate assemblage. We provided identical morphological and molecular datasets for species representing four genera to 40 taxonomic experts (10 per genus), who were asked to delimit species using (1) their preferred analytical approaches and (2) standardized analytical outputs. Total variance in species delimitation was partitioned into variance attributable to data analysis and interpretation of results. Total discordance was high (35.0%), and although standardization of analytical methods reduced discordance, substantial variance remained (23.5%) due to interpretative differences. Deviations from modal species estimates were not explained by any of seven expert attributes assessed, including taxonomic experience, publication record, geographic location, taxonomic concepts, or analytical methods. These results demonstrate that species delimitation can be subject to considerable subjectivity, even among experienced taxonomists working with identical data. Improving the precision of species delimitation will require coordinated advances across the full taxonomic workflow, including greater standardization of data acquisition and analysis, and clearer interpretative frameworks that explicitly define the evidentiary thresholds required to recognize species boundaries. Community-wide adoption of transparent reporting standards, analogous to those developed in genomics and clinical research, would help expose the sources of interpretative disagreement and facilitate more consistent application of species concepts across taxa and research groups. Developing benchmark datasets and shared reference taxonomies, against which new delimitation hypotheses can be evaluated, represents a tractable near-term goal for the systematic community. Ultimately, however, reproducible taxonomy cannot be achieved through procedural standardization alone. High-quality revisionary taxonomy must be grounded in experienced character evaluation and homology assessment, concept delimitation, and contingent analytical judgment, skills that are developed over years of immersive engagement with natural history collections, primary literature, and fieldwork. The decline of training opportunities in classical systematics therefore poses a direct threat not only to taxonomic productivity but to taxonomic consistency. Continued investment in a well-trained community of systematists, supported by institutions, collections, and funding agencies, remains the most reliable foundation for consistent and accurate species delimitation. Our results underscore that biodiversity metrics widely used in ecology, conservation planning, and macroevolutionary research are sensitive to practitioner variation in ways that have not previously been quantified, and that addressing this variation requires both methodological reform and sustained commitment to systematic expertise.

biodiversity↗