Multinomial goodness-of-fit: large sample tests with survey design correction and exact tests for small samples

I introduce the new mgof command to compute distributional tests for discrete (categorical, multinomial) variables. The command supports largesample tests for complex survey designs and exact tests for small samples as well as classic large-sample x2-approximation tests based on Pearson’s X2, the likelihood ratio, or any other statistic from the power-divergence family (Cressie and Read, 1984, Journal of the Royal Statistical Society, Series B (Methodological) 46: 440–464). The complex survey correction is based on the approach by Rao and Scott (1981, Journal of the American Statistical Association 76: 221–230) and parallels the survey design correction used for independence tests in svy: tabulate. mgof computes the exact tests by using Monte Carlo methods or exhaustive enumeration. mgof also provides an exact one-sample Kolmogorov–Smirnov test for discrete data.

Determinanten kognitiver Angstmanifestation während schulischer Tests: Eine Längsschnittstudie

Theoretischer Hintergrund und Fragestellung: Schulische Tests dienen der Feststellung von Wissen und Können. Wie jede Messung kann auch diese durch Störvariablen verzerrt werden. Während Tests erlebte Angst ist ein solcher potentieller Störeinfluss: Angst kann Testleistungen beinträchtigen, da sie sich hinderlich auf die Informationsverarbeitung auswirken kann (Störung des Wissensabrufs und des Denkens; Zeidner, 1998). Dieser kognitiven Angstmanifestation (Rost & Schermer, 1997) liegt die angstbedingte automatische Aufmerksamkeitsorientierung auf aufgaben-irrelevante Gedanken während der Testbearbeitung zugrunde (Eysenck, Derakshan, Santos & Calvo, 2007). Es hat sich allerdings gezeigt, dass Angst nicht grundsätzlich mit Testleistungseinbußen einhergeht (Eysenck et al., 2007). Wir gehen davon aus, dass die Kapazität zur Selbstkontrolle bzw. Aufmerksamkeitsregulation (Baumeister, Muraven & Tice, 2000; Schmeichel & Baumeister, 2010) ein Faktor ist, der bedingt, wie stark kognitive Angstmanifestation während Tests und damit zusammenhängende Leistungseinbußen auftreten. Ängstliche Lernende mit höherer Aufmerksamkeitsregulationskapazität sollten ihrer automatischen Aufmerksamkeitsorientierung auf aufgaben-irrelevante Gedanken erfolgreicher entgegensteuern und ihre Aufmerksamkeit weiterhin auf die Aufgabenbearbeitung richten können. Dem entsprechend sollten sie trotz Angst weniger kognitive Angstmanifestation während Tests erleben als ängstliche Lernende mit geringerer Aufmerksamkeitsregulationskapazität. Auch die Selbstwirksamkeitserwartung und das Selbstwertgefühl sind Variablen, die in der Vergangenheit mit der Bewältigung von Angst und Stress in Verbindung gebracht wurden (Bandura, 1977; Baumeister, Campbell, Krueger & Vohs, 2003). Daher wurden diese Variablen als weitere Prädiktoren berücksichtigt. Es wurde die Hypothese getestet, dass die dispositionelle Aufmerksamkeitsregulationskapazität über die dispositionelle Selbstwirksamkeitserwartung und das dispositionelle Selbstwertgefühl hinaus Veränderungen in der kognitiven Angstmanifestation während Mathematiktests in einer Wirtschaftsschülerstichprobe vorhersagt. Es wurde des Weiteren davon ausgegangen, dass eine indirekte Verbindung zwischen der Aufmerksamkeitsregulationskapazität und der Veränderung in den Mathematiknoten, vermittelt über die Veränderung in der kognitiven Angstmanifestation, besteht. Methode: Einhundertachtundfünfzig Wirtschaftsschüler bearbeiteten im September 2011 (T1) einen Fragebogen, der die folgenden Messungen enthielt:-Subskala Kognitive Angstmanifestation aus dem Differentiellen Leistungsangstinventar (Rost & Schermer, 1997) bezogen auf Mathematiktests (Sparfeldt, Schilling, Rost, Stelzl & Peipert, 2005); Alpha = .90; -Skala zur dispositionellen Aufmerksamkeitsregulationskapazität (Bertrams & Englert, 2013); Alpha = .88; -Skala zur Selbstwirksamkeitserwartung (Schwarzer & Jerusalem, 1995); Alpha = .83; -Skala zum Selbstwertgefühl (von Collani & Herzberg, 2003); Alpha = .83; -Angabe der letzten Mathematikzeugnisnote. Im Februar 2012 (T2), also nach 5 Monaten und kurz nach dem Erhalt des Halbjahreszeugnisses, gaben die Schüler erneut ihre kognitive Angstmanifestation während Mathematiktests (Alpha = .93) und ihre letzte Mathematikzeugnisnote an. Ergebnisse: Die Daten wurden mittels Korrelationsanalyse, multipler Regressionsanalyse und Bootstrapping ausgewertet. Die Aufmerksamkeitsregulationskapazität, die Selbstwirksamkeitserwartung und das Selbstwertgefühl (alle zu T1) waren positiv interkorreliert, r= .50/.59/.59. Diese Variablen wurden gemeinsam als Prädiktoren in ein Regressionsmodell zur Vorhersage der kognitiven Angstmanifestation zu T2 eingefügt. Gleichzeitig wurde die kognitive Angstmanifestation zu T1 konstant gehalten. Es zeigte sich, dass die Aufmerksamkeitsregulationskapazität erwartungskonform die Veränderungen in der kognitiven Angstmanifestation vorhersagte, Beta = -.21, p= .02. Das heißt, dass höhere Aufmerksamkeitsregulationskapazität zu T1 mit verringerter kognitiver Angstmanifestation zu T2 einherging. Die Selbstwirksamkeitserwartung, Beta = .12, p= .14, und das Selbstwertgefühl, Beta = .05, p= .54, hatten hingegen keinen eigenen Vorhersagewert für die Veränderungen in der kognitiven Angstmanifestation. Des Weiteren ergab eine Mediationsanalyse mittels Bootstrapping (bias-corrected bootstrap 95% confidence interval, 5000 resamples; siehe Hayes & Scharkow, in press), dass die Aufmerksamkeitsregulationskapazität (T1), vermittelt über die Veränderung in der kognitiven Angstmanifestation, indirekt mit der Veränderung in der Mathematikleistung verbunden war (d.h. das Bootstrap-Konfidenzintervall schloss nicht die Null ein; CI [0.01, 0.24]). Für die Selbstwirksamkeitserwartung und das Selbstwertgefühl fand sich keine analoge indirekte Verbindung zur Mathematikleistung. Fazit: Die Befunde verweisen auf die Bedeutsamkeit der Aufmerksamkeitsregulationskapazität für die Bewältigung kognitiver Angstreaktionen während schulischer Tests. Losgelöst von der Aufmerksamkeitsregulationskapazität scheinen positive Erwartungen und ein positives Selbstbild keine protektive Wirkung hinsichtlich der leistungsbeeinträchtigenden kognitiven Angstmanifestation während Mathematiktests zu besitzen.

Generation of a recombinant Gag virus-like-particle panel for the evaluation of p24 antigen detection by diagnostic HIV tests.

BACKGROUND Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens. METHODS We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection. RESULTS Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection. CONCLUSIONS The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.

Natural anti-FcepsilonRIalpha autoantibodies may interfere with diagnostic tests for autoimmune urticaria.

IgG autoantibodies against the alpha-chain of the high affinity IgE receptor are claimed to play a pathogenetic role in autoimmune urticaria. The best methods for detection of functional autoantibodies are currently the autologous serum skin test and the basophil histamine release assay. A simplified and feasible screening test would facilitate the diagnosis of autoimmune urticaria. Here we offer an explanation for the difficulties in establishing a screening test for autoantibodies directed against the alpha-chain of the high affinity IgE receptor in autoimmune urticaria. Identical autoantibodies in chronic urticaria patients and healthy donors belonging to the natural autoantibody repertoire were found by sequence analysis of anti-alpha-chain autoantibodies isolated by repertoire cloning from antibody libraries. These natural autoantibodies bound to the receptor and triggered histamine release but only if IgE was previously removed from the receptor. Diagnostic assays used for detection of antibodies directed against the IgE receptor may require signal comparison with and without the artificial removal of IgE, immune complexes, and complement in order to avoid false positive or negative results. After IgE removal diagnostic tests will detect natural autoantibodies against the high affinity IgE receptor regardless of whether they are pathogenic or not.

Performance of HBsAg point-of-care tests for detection of diagnostic escape-variants in clinical samples

BACKGROUND Hepatitis B viruses (HBV) harboring mutations in the a-determinant of the Hepatitis B surface antigen (HBsAg) are associated with reduced reactivity of HBsAg assays. OBJECTIVES To evaluate the sensitivity and specificity of three HBsAg point-of-care tests for the detection of HBsAg of viruses harboring HBsAg mutations. STUDY DESIGN A selection of 50 clinical plasma samples containing HBV with HBsAg mutations was used to evaluate the performance of three HBsAg point-of-care tests (Vikia(®), bioMérieux, Marcy-L'Étoile, France. Alere Determine HBsAg™, Iverness Biomedical Innovations, Köln, Germany. Quick Profile™, LumiQuick Diagnostics, California, USA) and compared to the ARCHITECT HBsAg Qualitative(®) assay (Abbott Laboratories, Sligo, Ireland). RESULTS The sensitivity of the point-of-care tests ranged from 98% to 100%. The only false-negative result occurred using the Quick Profile™ assay with a virus harboring a D144A mutation. CONCLUSIONS The evaluated point-of-care tests revealed an excellent sensitivity in detecting HBV samples harboring HBsAg mutations.

Reliability of Quantitative Sensory Tests in a Low Back Pain Population.

BACKGROUND AND OBJECTIVES Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and clinical practice, but information on reliability in patients with chronic pain is sparse. The aim of this study was to evaluate the reliability of different QST in patients with chronic low back pain. METHODS Eighty-nine patients with chronic low back pain participated in 2 identical experimental sessions, separated by at least 7 days. The following parameters were recorded: pressure pain detection and tolerance thresholds at the toe, electrical pain thresholds to single and repeated stimulation, heat pain detection and tolerance thresholds at the arm and leg, cold pain detection threshold at the arm and leg, and conditioned pain modulation using the cold pressor test.Reliability was analyzed using the coefficient of variation, the coefficient of repeatability, and the intraclass correlation coefficient. It was judged as acceptable or not based primarily on the analysis of the coefficient of repeatability. RESULTS The reliability of most tests was acceptable. Exceptions were cold pain detection thresholds at the leg and arm. CONCLUSIONS Most QST measurements have acceptable reliability in patients with chronic low back pain.

Quantum Nondemolition Measurement Enables Macroscopic Leggett-Garg Tests

We show how a test of macroscopic realism based on Leggett-Garg inequalities (LGIs) can be performed in a macroscopic system. Using a continuous-variable approach, we consider quantum nondemolition (QND) measurements applied to atomic ensembles undergoing magnetically driven coherent oscillation. We identify measurement schemes requiring only Gaussian states as inputs and giving a significant LGI violation with realistic experimental parameters and imperfections. The predicted violation is shown to be due to true quantum effects rather than to a classical invasivity of the measurement. Using QND measurements to tighten the “clumsiness loophole” forces the stubborn macrorealist to recreate quantum backaction in his or her account of measurement.

Confidence Bands for Isotonic Median Curves using Sign-Tests

Suppose that one observes independent random variables (X1, Y1), (X2, Y2), …, (Xn, Yn) in R2 with unknown distributions, except that Median(Yi | Xi = M(x) for some unknown isotonic function M. We describe an explicit algorithm for the computation of confidence bands for the median function M whose running time is of order O(n2). The bands rely on multiscale sign tests and are shown to have desirable asymptotic properties.

Application of Local Rank Tests for Nonparametric Regression

Let Y_i = f(x_i) + E_i\ (1\le i\le n) with given covariates x_1\lt x_2\lt \cdots\lt x_n , an unknown regression function f and independent random errors E_i with median zero. It is shown how to apply several linear rank test statistics simultaneously in order to test monotonicity of f in various regions and to identify its local extrema.