Informed Bayesian T-Tests

Across the empirical sciences, few statistical procedures rival the popularity of the frequentist t-test. In contrast, the Bayesian versions of the t-test have languished in obscurity. In recent years, however, the theoretical and practical advantages of the Bayesian t-test have become increasingly apparent and various Bayesian t-tests have been proposed, both objective ones (based on general desiderata) and subjective ones (based on expert knowledge). Here we propose a flexible t-prior for standardized effect size that allows computation of the Bayes factor by evaluating a single numerical integral. This specification contains previous objective and subjective t-test Bayes factors as special cases. Furthermore, we propose two measures for informed prior distributions that quantify the departure from the objective Bayes factor desiderata of predictive matching and information consistency. We illustrate the use of informed prior distributions based on an expert prior elicitation effort

A Tutorial on Fisher Information

In many statistical applications that concern mathematical psychologists, the concept of Fisher information plays an important role. In this tutorial we clarify the concept of Fisher information as it manifests itself across three different statistical paradigms. First, in the frequentist paradigm, Fisher information is used to construct hypothesis tests and confidence intervals using maximum likelihood estimators; second, in the Bayesian paradigm, Fisher information is used to define a default prior; lastly, in the minimum description length paradigm, Fisher information is used to measure model complexity

The Evaluation of an Educational Aiding Tool for Students Learning Logic

The subject of this thesis is the presentation and evaluation of Conan, an editor for writing natural deduction proofs in first-order logic. The intent is for the editor to serve as a supplementary tool alongside a course in logic. For this reason, emphasis was put on making sure the editor would have a low learning curve, ensuring that learning to use it would not take away from the limited time in a typical university course. Though editors for writing this kind of proof already exist, they are often cumbersome or difficult to use. A pre-study was conducted to determine that there is indeed a lack of editors that fulfil the requirements set forth in this thesis. The interface of Conan was evaluated both heuristically using Jakob Nielsen’s heuristics and also through limited user tests. This evaluation suggested that the interface was easy to use, quick to learn and that students were positive toward using the editor for writing proofs. We also present arguments for why Conan would be an aid from the perspective of pedagogy, though no in-depth research on this matter was conducted

Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

NKT Cells Stimulated by Long Fatty Acyl Chain Sulfatides Significantly Reduces the Incidence of Type 1 Diabetes in Nonobese Diabetic Mice

Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0, are enriched in the pancreas, their relative role in autoimmune diabetes is not known. Here, we report that sulfatide/CD1d-tetramer$^+$ cells accumulate in the draining pancreatic lymph nodes, and that treatment of NOD mice with sulfatide or C24:0 was more efficient than C16:0 in stimulating the NKT cell-mediated transfer of a delay in onset from T1D into NOD.Scid recipients. Using NOD.CD1d$^{−/−}$ mice, we show that this delay of T1D is CD1d-dependent. Interestingly, the latter delay or protection from T1D is associated with the enhanced secretion of IL-10 rather than IFN-g by C24:0-treated CD4$^+$ T cells and the deviation of the islet-reactive diabetogenic T cell response. Both C16:0 and C24:0 sulfatide isoforms are unable to activate and expand type I iNKT cells. Collectively, these data suggest that C24:0 stimulated type II NKT cells may regulate protection from T1D by activating DCs to secrete IL-10 and suppress the activation and expansion of type I iNKT cells and diabetogenic T cells. Our results raise the possibility that C24:0 may be used therapeutically to delay the onset and protect from T1D in humans

Renal Denervation Reduces Pulmonary Vascular Remodeling and Right Ventricular Diastolic Stiffness in Experimental Pulmonary Hypertension

Neurohormonal overactivation plays an important role in pulmonary hypertension (PH). In this context, renal denervation, which aims to inhibit the neurohormonal systems, may be a promising adjunct therapy in PH. In this proof-of-concept study, we have demonstrated in 2 experimental models of PH that renal denervation delayed disease progression, reduced pulmonary vascular remodeling, lowered right ventricular afterload, and decreased right ventricular diastolic stiffness, most likely by suppression of the renin-angiotensin-aldosterone system

Evidential Calibration of Confidence Intervals

We present a novel and easy-to-use method for calibrating error-rate based confidence intervals to evidence-based support intervals. Support intervals are obtained from inverting Bayes factors based on a parameter estimate and its standard error. A $k$ support interval can be interpreted as "the observed data are at least $k$ times more likely under the included parameter values than under a specified alternative". Support intervals depend on the specification of prior distributions for the parameter under the alternative, and we present several types that allow different forms of external knowledge to be encoded. We also show how prior specification can to some extent be avoided by considering a class of prior distributions and then computing so-called minimum support intervals which, for a given class of priors, have a one-to-one mapping with confidence intervals. We also illustrate how the sample size of a future study can be determined based on the concept of support. Finally, we show how the bound for the type I error rate of Bayes factors leads to a bound for the coverage of support intervals. An application to data from a clinical trial illustrates how support intervals can lead to inferences that are both intuitive and informative