Tea: A High-level Language and Runtime System for Automating Statistical Analysis

Though statistical analyses are centered on research questions and hypotheses, current statistical analysis tools are not. Users must first translate their hypotheses into specific statistical tests and then perform API calls with functions and parameters. To do so accurately requires that users have statistical expertise. To lower this barrier to valid, replicable statistical analysis, we introduce Tea, a high-level declarative language and runtime system. In Tea, users express their study design, any parametric assumptions, and their hypotheses. Tea compiles these high-level specifications into a constraint satisfaction problem that determines the set of valid statistical tests, and then executes them to test the hypothesis. We evaluate Tea using a suite of statistical analyses drawn from popular tutorials. We show that Tea generally matches the choices of experts while automatically switching to non-parametric tests when parametric assumptions are not met. We simulate the effect of mistakes made by non-expert users and show that Tea automatically avoids both false negatives and false positives that could be produced by the application of incorrect statistical tests.Comment: 11 page

Kiri Nikolai Fuss'ile

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Do Redundant Mutants Affect the Effectiveness and Efficiency of Mutation Analysis?

Abstract—Mutation analysis is an unbiased and powerful method for assessing input values and test oracles. However, in comparison to other techniques, such as those that rely on code coverage, it is a computationally-expensive and time-consuming method, especially for large software systems. This high cost is due, in part, to the fact that many mutation operators generate redundant mutants that may both misrepresent the mutation score and increase the runtime of the mutation analysis pro-cess. After showing how the conditional operator replacement (COR) mutation operator can be defined in a redundant-free manner, this paper uses four real-world programs, ranging in size from 3,000 to nearly 40,000 lines of code, to show the prevalence of redundant mutants. Focusing on the con-ditional operator replacement (COR) and relational operator replacement (ROR) mutation operators that create 41 % of all mutants in the chosen programs, the case study reveals that the removal of redundant mutants reduces the runtime of mutation analysis by up to 34%. Additional empirical results show that redundant mutants can lead to a mutation score that is misleadingly overestimated by as much as 10%. Overall, this paper convincingly demonstrates that it is possible to improve the effectiveness and efficiency of a mutation analysis system by identifying and removing redundant mutants. I

Somatostatin receptor 4 agonism normalizes stress-related excessive amygdala glutamate release and Pavlovian aversion learning and memory in rodents

Background Excessive processing of aversive life events is a major pathology in stress-related anxiety and depressive disorders. Current pharmacological treatments have rather non-specific mechanisms of action. Somatostatin is synthesized and released as an inhibitory co-neurotransmitter by specific GABA interneurons and one of its receptors, SSTR4, is localized in brain regions involved in adaptive aversion processing and implicated in negative valence neuropathology, including the amygdala. Methods Rat and mouse experiments were conducted to investigate effects of specific SSTR4 agonism on neurobehavioral aversion processing including any normalization of stress-related hyper-responsiveness. A mouse experiment to investigate stress and SSTR4 agonism effects on reward processing was also conducted. Results In male rats (N=5-10/group) fitted with glutamate biosensors in basolateral amygdala, SSTR4 agonism attenuated glutamate release to restraint stress in control rats and particularly in rats previously exposed to chronic corticosterone. In male mice (N=10-18/group), SSTR4 agonism dose-dependently attenuated Pavlovian tone-footshock learning and memory measured as freezing behavior, both in controls (CON) and following exposure to chronic social stress (CSS) which induces excessive Pavlovian aversion learning-memory. Specificity of SSTR4 agonism effects to aversion learning-memory was demonstrated by absence of effects on discriminative reward (sucrose) learning-memory in both CON and CSS mice; SSTR4 agonism did increase reward-to-effort valuation in a dose-dependent manner, and in both CON mice and mice exposed to CSS which attenuates reward motivation. Conclusions These neuropsychopharmacological findings add substantially to the preclinical proof-of-concept evidence for SSTR4 agonism as a treatment in anxiety and depressive disorders. Keywords Somatostatin receptor 4 Amygdala Stress Aversion Reward GABA interneuro

Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction

Background: We aimed to evaluate the diagnostic value of a positron emission tomography (PET)-measured heterogeneity in longitudinal myocardial blood flow (MBF) during cold pressor testing (CPT) and global MBF response to CPT from rest (ΔMBF) for identification of coronary vasomotor dysfunction. Methods and Results: In 35 patients CPT-induced alterations in epicardial luminal area were determined with quantitative angiography as the reference. MBF was assessed over the whole left ventricle as global MBF and regionally in the mid and mid-distal myocardium as MBF difference or MBF heterogeneity with nitrogen-13 ammonia and PET. The sensitivity and specificity of a longitudinal MBF difference during CPT in the identification of epicardial vasomotor dysfunction were significantly higher, than the global ΔMBF to CPT (88% vs 79% and 82% vs 64%, respectively; P<.05). Combining both parameters resulted in an optimal sensitivity of 100% at the expense of an intermediate specificity of 73%. The diagnostic accuracy was higher for the combined analysis than that for the MBF difference alone and global ΔMBF alone (91% vs 86% and 74%, respectively; P<.05). Conclusions: The combined evaluation of a CPT-induced heterogeneity in longitudinal MBF and the change in global MBF from rest may emerge as a new promising analytic approach to further optimize the identification and characterization of coronary vasomotor dysfunctio

The white spot syndrome virus DNA genome sequence

AbstractWhite spot syndrome virus (WSSV) is at present a major scourge to worldwide shrimp cultivation. We have determined the entire sequence of the double-stranded, circular DNA genome of WSSV, which contains 292,967 nucleotides encompassing 184 major open reading frames (ORFs). Only 6% of the WSSV ORFs have putative homologues in databases, mainly representing genes encoding enzymes for nucleotide metabolism, DNA replication, and protein modification. The remaining ORFs are mostly unassigned, except for five, which encode structural virion proteins. Unique features of WSSV are the presence of a very long ORF of 18,234 nucleotides, with unknown function, a collagen-like ORF, and nine regions, dispersed along the genome, each containing a variable number of 250-bp tandem repeats. The collective information on WSSV and the phylogenetic analysis on the viral DNA polymerase suggest that WSSV differs profoundly from all presently known viruses and that it is a representative of a new virus family

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe