Test Procedures in Configural Frequency Analysis (CFA) Controlling the Local and Multiple Level

The test statistics used until now in the CFA have been developed under the assumption of the overall hypothesis of total independence. Therefore, the multiple test procedures based on these statistics are really only different tests of the overall hypothesis. If one likes to test a special cell hypothesis, one should only assume that this hypothesis is true and not the whole overall hypothesis. Such cell tests can then be used as elements of a multiple test procedure. In this paper it is shown that the usual test procedures can be very anticonservative (except of the two-dimensional, and, for some procedures, the three-dimensional case), and corrected test procedures are developed. Furthermore, for the construction of multiple tests controlling the multiple level, modifications of Holm's (1979) procedure are proposed which lead to sharper results than his general procedure and can also be performed very easily.     

A Shift Algorithm for Exact Computation in Sequential Tests with Binary Outcome

A simple shift algorithm is described enabling the exact determination of power functions and sample size distributions for a large variety of closed sequential two‐sample designs with a binary outcome variable. The test statistics are assumed to be based on relative frequencies of successes or failures, but the number of interim analyses, the monitoring times, and the continuation regions may be specified as desired. To give examples, exact properties of designs proposed by the program package EaSt (Cytel , 1992) are determined, and plans with interim analyses are considered where decisions are based on the conditional power given the observations obtained so far.     

Neural correlates of effective learning in experienced medical decision-makers

Accurate associative learning is often hindered by confirmation bias and success-chasing, which together can conspire to produce or solidify false beliefs in the decision-maker. We performed functional magnetic resonance imaging in 35 experienced physicians, while they learned to choose between two treatments in a series of virtual patient encounters. We estimated a learning model for each subject based on their observed behavior and this model divided clearly into high performers and low performers. The high performers showed small, but equal learning rates for both successes (positive outcomes) and failures (no response to the drug). In contrast, low performers showed very large and asymmetric learning rates, learning significantly more from successes than failures; a tendency that led to sub-optimal treatment choices. Consistently with these behavioral findings, high performers showed larger, more sustained BOLD responses to failed vs. successful outcomes in the dorsolateral prefrontal cortex and inferior parietal lobule while low performers displayed the opposite response profile. Furthermore, participants' learning asymmetry correlated with anticipatory activation in the nucleus accumbens at trial onset, well before outcome presentation. Subjects with anticipatory activation in the nucleus accumbens showed more success-chasing during learning. These results suggest that high performers' brains achieve better outcomes by attending to informative failures during training, rather than chasing the reward value of successes. The differential brain activations between high and low performers could potentially be developed into biomarkers to identify efficient learners on novel decision tasks, in medical or other contexts.     

Therapeutic peptides revisited.

After a roller coaster ride of successes and failures, new discovery technologies and advances in manufacturing promise a brighter future for peptides in human therapy.     

Evaluating Chessboard MANOVA Designs Using Predictive and Matching Configural Frequency Analysis

This paper concerns the nonparametric evaluation of chessboard MANOVA designs. For this purpose, a matching procedure based on rook methodology is suggested as a complement to predictive coafigural frequency analysis. Using this procedure, a multivariate hypothesis can be tested in a single test. It is also possible to design a significance test to fit a specific composite hypothesis. The procedure is illustrated by results from a multivariate psychopharmacological experiment in which the effects of alcohol and caffeine were studied on test performance and volatility.     

Eradication of populations of an invasive ant in northern Australia: successes, failures and lessons for management

Eradication is the most difficult management goal for exotic species, and successes are rare and even more rarely published. The lack of publication of the methodology and outcomes of eradication programs severely limits the transfer of knowledge to programs elsewhere that target the same or similar species. Here I detail the successes and failures of eradication efforts on six populations of African big headed ant Pheidole megacephala in northern Australia, covering a combined area of almost 9 ha. Two years post-treatment, assessment criteria for successful eradication were met for four of the six populations, whereas eradication failed in the remaining two, resulting in the need for ongoing management. Positive outcomes are attributed to eight criteria being met: (1) a single line of project management authority; (2) over-arching legal authority; (3) susceptibility of the target organism to control procedures; (4) sufficient resources; (5) detectibility of the target organism at low densities; (6) early intervention; (7) prevention of reinvasion; and (8) prevention of invasive succession. Reasons for one of the failures remain unclear, but eradication failed in the other because a part of the population was not treated. In both cases, the eradication failures could have been detected and managed much earlier than was the case. The successes and lessons documented here, coupled with the now large number of small-scale eradications of this ant, warrant the implementation of larger and more ambitious management programs against this significant invader, especially within areas of high conservation value.     

Long-term Follow-up of Therapeutic Starvation

A total of 75 grossly obese patients were admitted to hospital for 80 episodes of prolonged starvation. Five took their own discharge within two weeks of admission and 12 defaulted from follow-up within 12 months of discharge. The others were all followed up for periods of 12 to 64 months. Altogether 39 episodes in 34 patients were classified as failures, eight as modified successes, and 16 as successes, though five of the latter patients subsequently defaulted. Success was associated with regular follow-up attendance but could not be otherwise predicted. A number of patients obtained tangible benefit from starvation despite a subsequent gain in weight.     

Human Health Risk Assessment: Required Reading

Over the past 30 years, risk assessment has developed into a scientific discipline. It is critical that the next generation of risk assessors understand the history of our field, and recognize the numerous successes and failures that have taken place. This short Perspective identifies and describes specific books, monographs, and reports that are required reading for any nascent risk assessor.     

Test Based on Independent,but Non-identically Distributed Random Variables

The binomial test is applied for the problem of testing a hypothesis based on a sample of independent, but non-identically distributed random variables. The used basic idea is that each random variable indicates the presence of the hypothesis. Hence each random variable is transformed such that the binomial test can be used as a simple procedure.     

Predictive ADMET studies, the challenges and the opportunities

Predictive ADMET is the new 'hip' area in drug discovery. The aim is to use large databases of ADMET data associated with structures to build computational models that link structural changes with changes in response, from which compounds with improved properties can be designed and predicted. These databases also provide the means to enable predictions of human ADMET properties to be made from human in vitro and animal in vivo ADMET measurements. Both methods are limited by the amount of data available to build such predictive models, the limitations of modelling methods and our understanding of the systems we wish to model. The current failures, successes and opportunities are reviewed.     

Simultaneous Non‐inferiority Test of Sensitivity and Specificity for Two Diagnostic Procedures in the Presence of a Gold Standard

Sensitivity and specificity have traditionally been used to assess the performance of a diagnostic procedure. Diagnostic procedures with both high sensitivity and high specificity are desirable, but these procedures are frequently too expensive, hazardous, and/or difficult to operate. A less sophisticated procedure may be preferred, if the loss of the sensitivity or specificity is determined to be clinically acceptable. This paper addresses the problem of simultaneous testing of sensitivity and specificity for an alternative test procedure with a reference test procedure when a gold standard is present. The hypothesis is formulated as a compound hypothesis of two non‐inferiority (one‐sided equivalence) tests. We present an asymptotic test statistic based on the restricted maximum likelihood estimate in the framework of comparing two correlated proportions under the prospective and retrospective sampling designs. The sample size and power of an asymptotic test statistic are derived. The actual type I error and power are calculated by enumerating the exact probabilities in the rejection region. For applications that require high sensitivity as well as high specificity, a large number of positive subjects and a large number of negative subjects are needed. We also propose a weighted sum statistic as an alternative test by comparing a combined measure of sensitivity and specificity of the two procedures. The sample size determination is independent of the sampling plan for the two tests.     

Optimal adaptive designs for binary response trials

Summary. We derive the optimal allocation between two treatments in a clinical trial based on the following optimality criterion: for fixed variance of the test statistic, what allocation minimizes the expected number of treatment failures? A sequential design is described that leads asymptotically to the optimal allocation and is compared with the randomized play‐the‐winner rule, sequential Neyman allocation, and equal allocation at similar power levels. We find that the sequential procedure generally results in fewer treatment failures than the other procedures, particularly when the success probabilities of treatments are smaller.     

Missing links: how individual’s can contribute to reserve policy enforcement on the example of the European Union

This comment looks at opportunities available to individuals alone or as a member of non-governmental organisations (NGOs) to enforce reserve policy at the EU level to improve the effectiveness of biodiversity conservation. Based on a literature review, recent developments in certain EU policies (i.e., Nature Conservation Policy, Common Agricultural Policy, Regional Policy, Århus—Public Participation and Access to Justice) are assessed by means of a SEPO analysis. SEPO is a French acronym that stands for the successes (succès), failures (echècs), potentials (potentialités), and obstacles (obstacles). This method aims to analyse a situation from four dimensions of the past (successes and failures) and future (potentials and obstacles). The analysis shows different ways in which individuals can contribute to reserve policy enforcement (i.e., by public interest complaint based on private rights) and identifies public funding opportunities for research and management of reserves. Some of these mechanisms have just recently been introduced (e.g., Århus rights and several funding opportunities). Not surprisingly, the widest set of opportunities is provided by the Nature Conservation Policy. The other three policies (Common Agricultural Policy, Regional Policy, Århus—Public Participation and Access to Justice) touch on reserve conservation only in an additional way, either horizontally or vertically. The analysis also identifies inter-linkages between the different policies with regard to reserve conservation, which may be used by individuals to enforce policy either in a protective or cooperative way.     

Tests of Bivariate Symmetry with a One-sided Alternative in the Analysis of Variance

We consider a two-factor experiment in which the factors have the same number of levels with a natural ordering among levels. We test the hypothesis that the effects of the two treatments are symmetric against a one-sided alternative using the likelihood ratio criteria. Test of the one-sided alternative as a null hypothesis against no restriction has also been studied. Exact distribution theory under the null hypothesis is derived and is shown to be a weighted mixture of chi-square distributions. An example is used to illustrate the procedure.     

TEMPERATURE-COMPENSATED TESTS FOR RAW MILK SUPPLIES. PART IV. STUDIES ON A KEEPING QUALITY TEST AT 19–20°

SUMMARY: A field-scale experiment carried out in Wales and the West Midlands, in which the temperature-compensated clot-on-boiling (C.O.B.) test of Rowlands & Hosking (1951) was applied to 11,626 samples of designated milk, morning, mixed and evening milk, gave proportions of failures in the ratio 1:2:3 respectively. Despite temperature compensation, failures varied according to atmospheric temperature from c. 50% at 72°F. or more to 10% at 56°F. or less and averaged 20% during the summer and 7% during the six winter months.
No marked differences were noted between the keeping qualities of tuberculin tested or accredited milk. During the winter no difference was found between producer-wholesaler and producer-retailer supplies, but the latter had a higher proportion of failures of evening and mixed milks during the summer.
In a set of 8,297 samples examined in addition by the methylene blue and coli-aerogenes tests, the C.O.B. test gave a lower incidence of failures than either the methylene blue or combined methylene blue and coli-aerogenes tests throughout almost the entire year. It is suggested that a temperature-compensated C.O.B. test is practicable as a routine procedure.     

What has de novo protein design taught us about protein folding and biophysics?

Recent progress in de novo protein design has led to an explosion of new protein structures, functions and assemblies. In this essay, I consider how the successes and failures in this new area inform our understanding of the proteins in nature and, more generally, the predictive computational modeling of biological systems.     

A General Framework for Formal Tests of Interaction after Exhaustive Search Methods with Applications to MDR and MDR-PDT

The initial presentation of multifactor dimensionality reduction (MDR) featured cross-validation to mitigate over-fitting, computationally efficient searches of the epistatic model space, and variable construction with constructive induction to alleviate the curse of dimensionality. However, the method was unable to differentiate association signals arising from true interactions from those due to independent main effects at individual loci. This issue leads to problems in inference and interpretability for the results from MDR and the family-based compliment the MDR-pedigree disequilibrium test (PDT). A suggestion from previous work was to fit regression models post hoc to specifically evaluate the null hypothesis of no interaction for MDR or MDR-PDT models. We demonstrate with simulation that fitting a regression model on the same data as that analyzed by MDR or MDR-PDT is not a valid test of interaction. This is likely to be true for any other procedure that searches for models, and then performs an uncorrected test for interaction. We also show with simulation that when strong main effects are present and the null hypothesis of no interaction is true, that MDR and MDR-PDT reject at far greater than the nominal rate. We also provide a valid regression-based permutation test procedure that specifically tests the null hypothesis of no interaction, and does not reject the null when only main effects are present. The regression-based permutation test implemented here conducts a valid test of interaction after a search for multilocus models, and can be applied to any method that conducts a search to find a multilocus model representing an interaction.     

"C.-E.A. Winslow and the early years of public health at Yale, 1915-1925"

C.-E.A. Winslow was the first chairman of the Department of Public Health at the Yale University School of Medicine. This paper considers the development and changing agenda of his department, the structure of Yale University, and the maturation of public health as a discipline. Winslow's successes and failures are discussed as they relate to Yale and external societal influences.     

Is Knowing the Age-Order of Alleles in a Sample Useful in Testing for Selective Neutrality?

The most powerful, and most frequently used, test of selective neutrality, based on data consisting of observed allelic frequencies in a sample of genes at some locus, is the procedure of G. A. Watterson. This procedure uses the sample homozygosity F* as the test statistic, and in effect leads to rejection of the hypothesis of selective neutrality if the observed value of F* differs significantly from neutral theory expectations. The homozygosity statistic is invariant under relabeling of the alleles and thus cannot use any further information on the alleles which might be available. We present results which suggest that information concerning the age order of the alleles cannot be used to provide a more powerful testing procedure than that of Watterson.     

Mouvances des familles et réponses aux besoins des enfants I. L’amour et la confiance de base

There are a lot of different models of family structures apart from the traditional nuclear family which is why they have been grouped together under the generic termrestructured families. Do they satisfactorily meet — to paraphrase Winnicott — the psychic needs of children that live inside them? The answer cannot be simplyyes or no as it is obviously impossible to study each individual case. Like all human institutions, these families have specific failures and successes, which may be momentary during a crisis or a highly productive period while others may be more structural. In the first of these two articles dedicated to this subject, the question of love given in response to the child’s expectations will be discussed, followed by a discussion of what happens to his self-confidence, which is in the process of being formed.