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Familial aggregation of chronic respiratory disease: use of National Health Interview Survey data for specific hypothesis testing.

The 1970 National Health Interview Survey included questions on respiratory disease and smoking habits. The new data were released in July 1974. Data consisted of information on approximately 116,000 persons from 37,000 households selected randomly from 357 primary sampling units. To test a hypothesis about familial clustering of chronic respiratory disease in households, we selected as index households those having an adult (aged 35-54 years) reporting a diagnosis of asthma, bronchitis, or emphysema and also having first order relatiaves less than age 35. Index households were matched with households from the same neighbourhood having an adult aged 35-54, of the same sex as the diseased person in the index household, without disease and with all other adults 35-54 without disease, and which had first order relatives less than 35 living in the same household. Analysis was carried out using Cochran's d-test to compare frequency of respiratory disease in persons less than 35 in each group. There was a strong association (P less than .001) between persons over 35 with chronic respiratory diseases and the disease rate in their first order relatives. The association could not be explained by differences in demographic variables and smoking habits.

Adolescent

The effects of introtacts on hypothesis testing in kindergarten and first-grade children.

Kindergarten and first-grade children were trained against their initial dimensional preference in a 2-dimensional simultaneous discrimination learning task. One third of the children received pretraining in using a sequential hypothesis-testing strategy, one third received pretraining in which they experienced solutions to tasks of the same type, and one third received no pretraining. Half of the children received introtact probes prior to each trial in the criterion task. Introtact probes had no effect on the performance of kindergarten children but facilitated the performance of first-grade children who received pretraining. Performance was generally better in the pretraining conditions than in the control condition and was generally better for first graders than for kindergarten children. Indices of the use of the sequential hypothesis-testing strategy were obtained from the responses to introtact probes. 75% of the first graders who received pretraining in hypothesis testing showed high proficiency in using the strategy, whereas only 38% of the kindergarten children did so. A strong tendency to become fixated on the irrelevant dimension was evident at both age levels.

Child

An assessment of hypothesis testing in mentally retarded adolescents.

Groups of educable and trainable institutionalised retarded adolescents were tested on a discrimination learning problem with a modified blank trials procedure in an attempt to measure their hierarchy of hypotheses. Results indicated that the hierarchy and size of initial hypothesis sets varied as a function of degree of retardation. Trainable retarded subjects had fewer hypotheses, and initially chose position hypotheses predominantly. Under discriminate reinforcement, most of these were readily switched to stimulus dimension hypotheses, which they retained during additional non-discriminate (100 per cent) reinforcement trials. Educable retarded subjects predominantly chose stimulus dimension hypotheses initially, and most of these switched to position hypotheses during either discriminate or non-discriminate reinforcement trials.

Adolescent

Use of statistics when examining lifetime studies in rodents to detect carcinogenicity.

The lifetime assay for carcinogenicity that subjects groups of 50 animals per sex per dose to three doses and a control is examined for its statistical properties. Using the standard formulation of tests of hypothesis, it is shown that there is a 20-50% chance of having a false positive and that it is possible to define a "weak carcinogen" in terms of the degree of effect that would produce a false negative less than 5% of the time. Whether hypothesis testing is a proper use of statistics in this context is questioned, and alternatives are proposed.

Animals

Long-term survival of cardiac allografts in lethally irradiated rats repopulated with host-type hemopoietic cells.

To test the hypothesis that hemopoietic cells within a tissue graft are responsible for its immunogenicity, two experimental protocols were followed. LEW hearts were grafted into (LEW X BN)F-1 host rats and LEW or F-1 lymphocytes were injected into the apex of the grafted heart. The LEW but not the F-1 cells induced a local reaction, apparently because the circulating F-1 cells were the necessary immunogens. The second protocol took advantage of the knowledge that lethally irradiated LEW rats were able to reject WF Ag-B-incompatible hemopoietic cells (but not tissue allografts) within a few days. LEW rats were lethally irradiated and grafted with WF hearts on day 0. A mixture of LEW marrow, thymus, spleen and lymph node cells, or marrow cells only were infused either on day 0 or day 2. Cardiac allografts in hosts repopulated with the mixture of lymphoid cells survived a mean of 11.3 days in hosts infused on day 0, but survived indefinitely if the lymphoid cells were infused on day 2. The 2-day interval also prolonged the survival of allografts in rats infused with only marrow cells. The long-term recipients, without any further treatment, rejected WF skin grafts as first-set reactions 1 year later but did not reject second WF cardiac allografts. Lymphoid cells from long-term recipients imparied the rejection of WF cardiac allografts by LEW host rats. The lack of rejection of the original cardiac allograft supported the hypothesis tested. Certain hemopoietic cells responsible for the immunogenicity of cardiac allografts were probably eliminated in the 2-day interval at least in part by host effector cells capable of rejecting allogeneic hemopoietic cells. However, the mechanism of long-term "unresponsiveness" to WF hearts could have been caused by loss of accessory cells during the 2-day interval followed by infusion of immunocompetent cells. Skin rejections in these recipients may have been attributable to reactions against skin differentiation-specific antigens.

Animals

Replication of "speech fluency fluctuations during the menstrual cycle".

This study tested the hypothesis suggested by our earlier research that the principal effect of heightened anxiety on speech fluency is an interference with language formulation. 20 women read contexual material aloud at ovulation (when the typical woman experiences her greatest feelings of well-being) and at premenstrution (when she experiences a significant increase in anxiety level). They were no less fluent at premenstruation than at ovulation. These data are consistent with the hypothesis tested.

Adult

Simultaneous inference for generalized linear models with unmeasured confounders.

Tens of thousands of simultaneous hypothesis tests are routinely performed in genomic studies to identify differentially expressed genes. However, due to unmeasured confounders, many standard statistical approaches may be substantially biased. This paper investigates the large-scale hypothesis testing problem for multivariate generalized linear models in the presence of confounding effects. Under arbitrary confounding mechanisms, we propose a unified statistical estimation and inference framework that harnesses orthogonal structures and integrates linear projections into three key stages. It begins by disentangling marginal and uncorrelated confounding effects to recover the latent coefficients. Subsequently, latent factors and primary effects are jointly estimated through lasso-type optimization. Finally, we incorporate projected and weighted bias-correction steps for hypothesis testing. Theoretically, we establish the identification conditions of various effects and non-asymptotic error bounds. We show effective Type-I error control of asymptotic-tests as sample and response sizes approach infinity. Numerical experiments demonstrate that the proposed method controls the false discovery rate by the Benjamini-Hochberg procedure and is more powerful than alternative methods. By comparing single-cell RNA-seq counts from two groups of samples, we demonstrate the suitability of adjusting confounding effects when significant covariates are absent from the model.

Hidden variables

Statistical aspects of comparative bioavailability trials.

The role of comparative bioavailability trials in testing for the bioequivalence of different formulations of a drug is discussed and the statistical aspects of the design and analysis of such trials are reviewed. It is suggested that the design of such trials presents no special problem but that the customary method of analysis, which tests the null hypothesis of no difference between the formulations, is irrelevant to the central purpose of such trials, which is to determine whether the formulations have essentially equivalent therapeutic effects. It is proposed that only those characteristics of the data that possess a meaningful relation to the therapeutic use of the drug should be analysed and also that estimation procedures rather than hypothesis testing techniques should be employed. Several aspects of the statistics of bioavailability trials which require further investigation are listed.

Biological Availability

Immunogenetic aspects of nasopharyngeal carcinoma (NPC) III. HL-a type as a genetic marker of NPC predisposition to test the hypothesis that Epstein-Barr virus is an etiological factor in NPC.

HL-A typing of 144 NPC patients and 236 controls revealed an increased frequency of 1st locus HL-42 (relative risk = 2.24) and an increased frequency of unidentified antigens at the 2nd locus (relative risk = 2.60) in the NPC patients. HL-A2 and the 2nd locus "blank" appeared to act together (HL-A2 blank haplotype) in determining NPC risk in highest-risk Cantonese, whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently. Only the "blank" had an increased frequency in Malay NPC patients. Thus there was an indication that the strength of the HL-A association with NPC reflected the 30-50-fold difference in incidence between highest-risk Cantonese and lowest-risk Indians. In Singapore, HL-A segregation patterns in families of nine Chinese NPC patients confirmed that the "blank" was a genetic phenomenon. A new 2nd locus antigen (Singapore-2) has recently been detected. Singapore-2 occurs more frequently in NPC patients and appears to be associated with a high risk for NPC. Since HL-A2 and Singapore-2 are not the risk factors, it is likely that the HL-A association with NPC reflects the existence of disease-susceptibility (DS) genes in linkage disequilibrium with alleles of the HL-A loci. It is proposed that NPC-DS genes may determine differences in immune responsiveness to environmental agents, and thereby determine differences in NPC incidence. If the known altered immune responsiveness of NPC patients to EBV reflects the function of DS genes linked to the high NPC risk HL-A type, then the hypothesis that Epstein-Barr virus has an etiological role in NPC can be tested by several types of prospective studies.

Carcinoma

Formal education and intellectual functioning in the immigrant Cuban elderly.

Formal educational experience during childhood and adolescence is an important modifier of intellectual functioning in North American elderly populations. The culture-independence of this relationship was examined with 31 immigrant Cuban elderly men and women who received their education in Cuba. The amount of formal education was significantly related to performance on measures of classification, combinatorial analysis (males only), hypothesis testing, and matrices. An index of fluid intelligence (matrices) also was significantly related to performance on the classification and hypothesis testing tasks. All participants conserved both liquid and mass, thus showing no regression on these two concerete operational tasks.

Aged

A Bayesian framework for multivariate differential analysis.

Differential analysis is a routine procedure in the statistical analysis toolbox across many applied fields, including quantitative proteomics, the main illustration of the present paper. The state-of-the-art limma approach uses a hierarchical formulation with moderated-variance estimators for each analyte directly injected into the t-statistic. While standard hypothesis testing strategies are recognised for their low computational cost, allowing for quick extraction of the most differential among thousands of elements, they generally overlook key aspects such as handling missing values, inter-element correlations, and uncertainty quantification. The present paper proposes a fully Bayesian framework for differential analysis, leveraging a conjugate hierarchical formulation for both the mean and the variance. Inference is performed by computing the posterior distribution of compared experimental conditions and sampling from the distribution of differences. This approach provides well-calibrated uncertainty quantification at a similar computational cost as hypothesis testing by leveraging closed-form equations. Furthermore, a natural extension enables multivariate differential analysis that accounts for possible inter-element correlations. We also demonstrate that, in this Bayesian treatment, missing at random data should generally be ignored in univariate settings, and further derive a tailored approximation that handles multiple imputation for the multivariate setting. We argue that probabilistic statements in terms of effect size and associated uncertainty are better suited to practical decision-making. Therefore, we finally propose simple and intuitive inference criteria, such as the overlap coefficient, which express group similarity as a probability rather than traditional, and often misleading, p-values. The performance of this approach is evaluated through an extensive empirical study using both synthetic and controlled real-world proteomics datasets. Overall, we believe that this Bayesian framework for (multivariate) differential analysis provides a valuable and intuitive counterpart to standard methods at a comparable computational cost.

Bayes Theorem