Modelling for understanding AND for prediction/classification - the power of neural networks in research

Two articles, Edelsbrunner and, Schneider (2013), and Nokelainen and Silander (2014) comment on Musso, Kyndt, Cascallar, and Dochy (2013). Several relevant issues are raised and some important clarifications are made in response to both commentaries. Predictive systems based on artificial neural networks continue to be the focus of current research and several advances have improved the model building and the interpretation of the resulting neural network models. What is needed is the courage and open-mindedness to actually explore new paths and rigorously apply new methodologies which can perhaps, sometimes unexpectedly, provide new conceptualisations and tools for theoretical advancement and practical applied research. This is particularly true in the fields of educational science and social sciences, where the complexity of the problems to be solved requires the exploration of proven methods and new methods, the latter usually not among the common arsenal of tools of neither practitioners nor researchers in these fields. This response will enrich the understanding of the predictive systems methodology proposed by the authors and clarify the application of the procedure, as well as give a perspective on its place among other predictive approaches

Predicting general academic performance and identifying the differential contribution of participating variables using artificial neural networks

oai:flr.journals.publicknowledgeproject.org:article/13Many studies have explored the contribution of different factors from diverse theoretical perspectives to the explanation of academic performance. These factors have been identified as having important implications not only for the study of learning processes, but also as tools for improving curriculum designs, tutorial systems, and students’ outcomes. Some authors have suggested that traditional statistical methods do not always yield accurate predictions and/or classifications (Everson, 1995; Garson, 1998). This paper explores a relatively new methodological approach for the field of learning and education, but which is widely used in other areas, such as computational sciences, engineering and economics. This study uses cognitive and non-cognitive measures of students, together with background information, in order to design predictive models of student performance using artificial neural networks (ANN). These predictions of performance constitute a true predictive classification of academic performance over time, a year in advance of the actual observed measure of academic performance. A total sample of 864 university students of both genders, ages ranging between 18 and 25 was used. Three neural network models were developed. Two of the models (identifying the top 33% and the lowest 33% groups, respectively) were able to reach 100% correct identification of all students in each of the two groups. The third model (identifying low, mid and high performance levels) reached precisions from 87% to 100% for the three groups. Analyses also explored the predicted outcomes at an individual level, and their correlations with the observed results, as a continuous variable for the whole group of students. Results demonstrate the greater accuracy of the ANN compared to traditional methods such as discriminant analyses.  In addition, the ANN provided information on those predictors that best explained the different levels of expected performance. Thus, results have allowed the identification of the specific influence of each pattern of variables on different levels of academic performance, providing a better understanding of the variables with the greatest impact on individual learning processes, and of those factors that best explain these processes for different academic levels

Genomic Comparison, Phylogeny and Taxonomic Reevaluation of the Ectothiorhodospiraceae and Description of Halorhodospiraceae fam. nov. and Halochlorospira gen. nov.

The Ectothiorhodospiraceae family represents purple sulfur bacteria of the Gammaproteobacteria found primarily in alkaline soda lakes of moderate to extremely high salinity. The main microscopi-cally visible characteristic separating them from the Chromatiaceae is the excretion of the intermediate elemental sulfur formed during oxidation of sulfide prior to complete oxidation to sulfate rather than storing it in the periplasm. We present a comparative study of 38 genomes of all species of phototrophic Ectothiorhodospiraceae. We also include a comparison with those chemotrophic bacteria that have been assigned to the family previously and critically reevaluate this assignment. The data demonstrate the separation of Halorhodospira species in a major phylogenetic branch distant from other Ectothiorhodospiraceae and support their separation into a new family, for which the name Halorho-dospiraceae fam. nov. is proposed. In addition, the green-colored, bacteriochlorophyll-containing species Halorhodospira halochloris and Halorhodospira abdelmalekii were transferred to the new genus Halochlorospira gen. nov. of this family. The data also enable classification of several so far unclassified isolates and support the separation of Ectothiorhodospira shaposhnikovii and Ect. vacuolata as well as Ect. mobilis and Ect. marismortui as distinct species

Comparative Genome Analysis of the Photosynthetic Betaproteobacteria of the Genus Rhodocyclus: Heterogeneity within Strains Assigned to Rhodocyclus tenuis and Description of Rhodocyclus gracilis sp. nov. as a New Species

The genome sequences for Rhodocyclus purpureus DSM 168T and four strains assigned to Rhodocyclus tenuis (DSM 110, DSM 111, DSM 112, and IM 230) have been determined. One of the strains studied (IM 230) has an average nucleotide identity (ANI) of 97% to the recently reported genome of the type strain DSM 109 of Rcy. tenuis and is regarded as virtually identical at the species level. The ANI of 80% for three other strains (DSM 110, DSM 111, DSM 112) to the type strain of Rcy. tenuis points to a differentiation of these at the species level. Rcy. purpureus is equidistant from Rcy. tenuis and the new species, based on both ANI (78–80%) and complete proteome comparisons (70% AAI). Strains DSM 110, DSM 111, and DSM 112 are very closely related to each other based on ANI, whole genome, and proteome comparisons but clearly distinct from the Rcy. tenuis type strain DSM 109. In addition to the whole genome differentiation, these three strains also contain unique genetic differences in cytochrome genes and contain genes for an anaerobic cobalamin synthesis pathway that is lacking from both Rcy. tenuis and Rcy. purpureus. Based on genomic and genetic differences, these three strains should be considered to represent a new species, which is distinctly different from both Rcy. purpureus and Rcy. tenuis, for which the new name Rhodocyclus gracilis sp. nov. is proposed

Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra

Diagnosing collaboration in practice-based learning: Equality and intra-individual variability of physical interactivity

Collaborative problem solving (CPS), as a teaching and learning approach, is considered to have the potential to improve some of the most important skills to prepare students for their future. CPS often differs in its nature, practice, and learning outcomes from other kinds of peer learning approaches, including peer tutoring and cooperation; and it is important to establish what identifies collaboration in problem-solving situations. The identification of indicators of collaboration is a challenging task. However, students physical interactivity can hold clues of such indicators. In this paper, we investigate two non-verbal indexes of student physical interactivity to interpret collaboration in practice-based learning environments: equality and intra-individual variability. Our data was generated from twelve groups of three Engineering students working on open-ended tasks using a learning analytics system. The results show that high collaboration groups have member students who present high and equal amounts of physical interactivity and low and equal amounts of intra-individual variability

Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies