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Biomedical subjects

A Agresti

Publications and source records attributed to A Agresti.

At least 37 records · Page 2Linked to original sources

To E or not to E? Can an IL-4-induced B cell choose between IgE and IgG4?

Parasite immunologists had known for some time that IgE-mediated hypersensitivity reactions are rare in patients with chronic helminth infections, even though basophils and mast cells in these patients are sensitized with antiparasite IgE and exposed, often continuously, to parasite antigens. The inhibition of allergic reactivity in chronic helminth infections is mainly due to IgG4 'blocking antibodies' in the serum of the infected individual. IgG4 do not fix complement and bind weakly to Fcgamma receptors. Thus, antigen binding by IgG4, unlike IgE, is likely to have no or minimally harmful consequences. The discovery that, similar to IgE, expression of IgG4 is IL-4-dependent and is an intermediate step in sequential switching from IgM to IgE makes it imperative to understand how the two isotypes are coregulated and whether the two responses can be uncoupled, selectively boosting IgG4 over IgE. The ultimate goal is to apply to allergy the lesson we learnt from helminth infections.

Animals↗

A review of tests for detecting a monotone dose-response relationship with ordinal response data.

This tutorial reviews methods for testing independence between discrete levels of a dose and an ordered categorical response variable. The tests are designed to be powerful for cases in which the response improves monotonically as dosage level increases. First, we show how to apply some standard tests for doubly-ordered contingency tables. Then, we show how to construct tests as part of a model-building strategy. Other topics discussed include generalizations to stratified data, small-sample methods, and sample size and power considerations.

Dose-Response Relationship, Drug↗

The Halstead Category Test: a fifty year perspective.

The Category Test, a major part of the Halstead-Reitan Neuropsychological Battery, was first described in a 1943 article by Halstead and Settlage. This paper reviews the development of the test, the psychometric properties of the instrument, available administration and scoring methods, discusses various interpretative strategies, and the empirical support for the test's clinical validity. Recent developments are then reviewed, as well as what the authors see as the future potential for this instrument.

Brain Damage, Chronic↗

Molecular characterization of a variant of proviral bovine leukaemia virus (BLV).

Southern-blot hybridization and partial sequencing of the pol and env genes were used to characterize BLV-integrated provirus of seropositive cattle from two dairy herds in northern Italy. Comparison of the data obtained with those of previously characterized BLV strains from other geographic areas (Australia, Belgium, Japan and USA) revealed the presence of a viral variant (BLV-12), which showed both conserved and unique features. Regarding the gp51 envelope glycoprotein, the BLV-12 variant showed: 1. A high extent of conservation, which included potential glycosylation sites and cysteine residues; 2. Three unique amino acid residues not present in any of the other BLV strains analysed; and 3. Some variability at the level of one (G) of the three (F, G and H) conformational epitopes, which is probably important in the process of infection. These results agree with the suggestion that the sequence variability of the gp51 glycoprotein preferentially involves structures whose change is thought to underlie the phenomenon of escape from immune surveillance.

Amino Acid Sequence↗

Order-restricted tests for stratified comparisons of binomial proportions.

The data set presented relates a binomial response to ordered levels of an explanatory variable, representing doses of a drug, with data collected at several centers. A study goal is to test independence of the response and the ordinal factor, assuming under the alternative only that the binomial parameter is a monotonically increasing function of the ordinal predictor. We present two likelihood-ratio tests that are sensitive to order-restricted alternatives. Simulating the exact distributions of the test statistics yields nearly exact P-values. We also discuss related analyses for comparing two groups on an ordinal response, and we propose a test that is sensitive to a stochastic ordering alternative.

Binomial Distribution↗

Mantel-Haenszel-type inference for cumulative odds ratios with a stratified ordinal response.

This article proposes a Mantel-Haenszel-type estimator of an assumed common cumulative odds ratio in a proportional odds model for an ordinal response with several 2 x c contingency tables. It is useful, for instance, for comparing two treatments on an ordinal response for data from several centers when the data are highly sparse. The estimator has behavior similar to the Mantel-Haenszel estimator of a common odds ratio for several 2 x 2 tables. It is consistent under the ordinary asymptotic framework in which the number of tables is fixed and, unlike the maximum likelihood (ML) estimator, also under sparse asymptotics in which the number of tables grows with the sample size. Simulations reveal a considerable difference between it and the ML estimator when each table has few observations. Efficiency comparisons suggest that little efficiency loss occurs compared to the ML estimator when the data are not sparse. Tests and estimators are presented for detecting and handling heterogeneity in the odds ratios, and generalizations are available for stratified r x c contingency tables.

Asthma↗

Analysis of GC-rich repetitive nucleotide sequences in great apes.

The genomes of four primate species, belonging to the families Pongidae (chimpanzee, gorilla, and orangutan) and Hylobatidae (gibbons), have been analyzed for the presence and organization of two human GC-rich heterochromatic repetitive sequences: beta Satellite (beta Sat) and LongSau (LSau) repeats. By Southern blot hybridization and PCR, both families of repeats were detected in all the analyzed species, thus indicating their origin in an ape ancestor. In the chimpanzee and gorilla, as in man, beta Sat sequences showed a 68-bp Sau3A periodicity and were preferentially organized in large clusters, whereas in the orangutan, they were organized in DNA fragments of 550 bp, which did not seem to be characterized by a tandem organization. On the contrary, in each of the analyzed species, the bulk of LSau sequences showed a longer Sau3A periodicity than that observed in man (450-550 bp). Furthermore, only in the chimpanzee genome some of LSau repeats seemed to be interspersed within blocks of beta Sat sequences. This sequence organization, which also characterizes the human genome, is probably absent in the gorilla. In fact, the analysis of a gorilla genomic library suggested that LSau repeats are not preferentially in linkage with beta Sat sequences. Moreover, LSau sequences were found in a genomic sector characterized by the simultaneous presence of L1 and (CA) repeats, as well as of anonymous sequences and known genes. In spite of the different sequence organization, the nucleotide differences between complete human and gorilla LSau repeats were very few, whereas one gorilla LSau repeat, interrupted by a probably-truncated L1 transposon, showed a higher degree of divergence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Simple capture-recapture models permitting unequal catchability and variable sampling effort.

We consider two capture-recapture models that imply that the logit of the probability of capture is an additive function of an animal catchability parameter and a parameter reflecting the sampling effort. The models are special cases of the Rasch model, and satisfy the property of quasi-symmetry. One model is log-linear and the other is a latent class model. For the log-linear model, point and interval estimates of the population size are easily obtained using standard software, such as GLIM.

Animals↗

Distribution-free fitting of logit models with random effects for repeated categorical responses.

This article discusses random effects models for within-subject comparisons of repeated responses on the same categorical scale. The models account for the correlation that normally occurs between repeated responses. The standard way of fitting such models maximizes the marginal likelihood after integrating with respect to a distribution for the random effect. An alternative non-parametric approach does not assume a distributional form for the random effects. Recent literature shows that for certain simple logit models, this approach yields essentially the same model parameter estimates as conditional maximum likelihood. Moreover, these estimates also result from fitting corresponding quasi-symmetric log-linear models. For simple data sets in which primary interest relates to subject-specific comparisons of the repeated responses, one can easily obtain the estimates with standard software for log-linear models. Examples include data from crossover designs and from comparisons of treatment and control groups regarding the change between baseline and follow-up observations.

Clinical Trials as Topic↗

Molecular organization and chromosomal location of human GC-rich heterochromatic blocks.

From the sequencing of three genomic DNA fragments and PCR amplification products from total human DNA, we have derived the sequence of a 545-bp Sau3A fragment (68% GC), representative of a family of human DNA repeats. Since previous studies suggested its linkage with unrelated Sau3A repeats of 68 bp (54% GC) (beta-satellite sequences), this feature was further investigated by in situ hybridization experiments and by Southern blot analysis of a panel of DNAs from human-Chinese hamster somatic cell hybrids. Both DNA repeats are preferentially localized on the heterochromatic regions of acrocentric chromosomes, on the pericentromeric heterochromatin of chromosome 1, 3 and 9, and on the proximal euchromatic region of the chromosome Y q arm. On chromosome 9, both repeats are part of a 2.7-kb higher-order repeat unit. These results and the Southern blot analysis on partial digests of total DNA, suggest that the linkage between the two repetitive DNA sequences is a constant feature throughout the genome. Furthermore, Southern blot analysis of HpaII-digested and MspI-digested DNA from different human tissues and tumor cell lines indicates that the investigated heterochromatic blocks appear to be subjected to changes in their methylation pattern.

Base Sequence↗

Expression of beta 2m-free HLA class I heavy chains in neuroblastoma cell lines.

Flow cytometry with the specific monoclonal antibody (MoAb) L31 was used to analyse the expression of HLA class I heavy chains not bound with beta 2-microglobulin (beta 2m) by neuroblastoma (NB) cell lines IMR-32 and LA-N-1. The cells, which express barely detectable amounts of beta 2m-free (L31-positive molecules) and beta 2m-complexed HLA class I antigens (W6.32- and BBM.1-reactive molecules), expressed MHC class I molecules not bound to light chains upon differentiation with either retinoic acid or serum starvation. The expression was not accompanied by an increase of surface heterodimers. Conversely, recombinant interferon-gamma (rIFN-gamma) treatment led IMR-32 and LA-N-1 cells to almost exclusively express beta 2m-complexes HLA class I heavy chains. Surface beta 2m-free MHC class I molecules displayed a molecular mass of approximately 45 kDa and did not bind exogenously added beta 2m. No changes in the synthesis of either HLA class I and beta 2m mRNAs or of L31 proteins were observed in differentiated NB cells, thus suggesting that the surface exposure of unusual HLA class I antigens is regulated post-translationally. These findings indicate that, in addition to activated lymphocytes, the surface expression of beta 2m-free class I heavy chains is a feature of other cell types, such as NB cells.

Antigens, Surface↗

Use of polymerase chain reaction to diagnose bovine leukemia virus infection in calves at birth.

A specific polymerase chain reaction (PCR) assay was devised, allowing detection of 1 bovine leukemia virus (BLV)-infected cell in 10(4) bovine lymphocytes. The efficacy of field application of the developed method was verified by evaluating the rate of viral transmission to calves from infected cows, whether they have persistent lymphocytosis. With this objective, 43 calves were simultaneously tested at birth and at 6 months of age for viral antibodies in serum and for proviral DNA in lymphocytes. At birth, 36 calves were BLV-negative and 3 were BLV-positive by results of serologic and DNA-based assays. Conversely, results for 4 calves had lack of correlation between the diagnostic methods. In particular, 2 calves were DNA-positive and antibody-negative for BLV and 2 other calves had the opposite test results. At 6 months of age, when the immunologic pattern more closely reflects the status of calves' immune response, independent of maternal antibodies, all calves DNA-negative for BLV at birth (n = 38), were consistently PCR- and antibody-negative for BLV. On the contrary, the cattle DNA-positive for BLV at birth (n = 5), whether seropositive or not, were PCR- and antibody-positive for BLV, at the time of the second screening. Thus, these results indicate reliability of the PCR to diagnose perinatal BLV infection. Furthermore, the observation that all calves found to be infected at birth were born to BLV-positive cows with persistent lymphocytosis, indicates that the persistent lymphocytosis status of the cow may represent a factor associated with BLV infection in utero.

Animals↗

Quasi-symmetric latent class models, with application to rater agreement.

Suppose we observe responses on several categorical variables having the same scale. We consider latent class models for the joint classification that satisfy quasi-symmetry. The models apply when subject-specific response distributions are such that (i) for a given subject, responses on different variables are independent, and (ii) odds ratios comparing marginal distributions of the variables are identical for each subject. These assumptions are often reasonable in modeling multirater agreement, when a sample of subjects is rated independently by different observers. In this application, the model parameters describe two components of agreement--strength of association between classifications by pairs of observers and degree of heterogeneity among the observers' marginal distributions. We illustrate the models by analyzing a data set in which seven pathologists classified 118 subjects in terms of presence or absence of carcinoma, yielding seven categorical classifications with the same binary scale. A good-fitting model has a latent classification that differentiates between subjects on whom there is agreement and subjects on whom there is disagreement.

Biometry↗

Log-linear modelling of pairwise interobserver agreement on a categorical scale.

This article uses log-linear models to describe pairwise agreement among several raters who classify a sample on a subjective categorical scale. The models describe agreement structure simultaneously for second-order marginal tables of a multidimensional cross-classification of ratings. Practical difficulties arise in fitting the models, because models refer to pairwise marginal tables of a very large and sparse table. A standard analysis that treats the marginal tables as independent yields consistent estimates of model parameters, but not of the covariance matrix of the estimates. We estimate the covariance matrix using the jackknife. We apply the models to describe agreement between evaluations made by seven pathologists of carcinoma in situ of the uterine cervix, using a five-level ordinal scale. Previous analyses showed differences among the pathologists in their pairwise levels of agreement, but we observe near homogeneity in the dependence structure of their ratings.

Carcinoma in Situ↗

Modelling patterns of agreement and disagreement.

This article presents a survey of ways of statistically modelling patterns of observer agreement and disagreement. Main emphasis is placed on modelling inter-observer agreement for categorical responses, both for nominal and ordinal response scales. Models discussed include (1) simple cell-probability models based on Cohen's kappa that focus on beyond-chance agreement, (2) loglinear models for square tables, such as quasi-independence and quasi-symmetry models, (3) latent class models that express the joint distribution between ratings as a mixture of clusters for homogeneous subjects, each cluster having the same 'true' rating, and 4) Rasch models, which decompose subject-by-observer rating distributions using observer and subject main effects. Models can address two distinct components of agreement--strength of association between ratings, and similarity of marginal distributions of the ratings.

Linear Models↗