Nonmath Analogies in Teaching Mathematics

Way too often, students find some concepts too abstract to comprehend. One of the strategies used to assist students with building conceptual knowledge is to use analogies. We investigate the place of nonmath analogies in teaching school mathematics. First, we demonstrate the widespread use of analogies by drawing examples through context analysis of tutoring websites, textbooks, and teaching experiences. Second, we argue that analogies reflect the grounded nature of mathematical concepts in common life experiences and, thus, have an essential place in instruction. To support our argument we offer a theoretical rationale based on research literature and historical sources

Selection of Apps for Teaching Difficult Mathematics Topics: An Instrument to Evaluate Touch-Screen Tablet and Smartphone Mathematics Apps

Manipulatives—including the more recent touch-screen mobile device apps—belong to a broader network of learning tools. As teachers continue to search for learning materials that aid children to think mathematically, they are faced with a challenge of how to select materials that meet the needs of students. The profusion of virtual learning tools available via the Internet magnifies this challenge. What criteria could teachers use when choosing useful manipulatives? In this chapter, we share an evaluation instrument for teachers to use to evaluate apps. The dimensions of the instrument include: (a) the nature of the curriculum addressed in the app— emergent, adaptable or prescriptive, and relevance to current, high quality curricula—high, medium, low; (b) degree of actions and interactions afforded by the app as a learning tool— constructive, manipulable, or instructive interface; (c) the level of interactivity and range of options offered to the user —multiple or mono, or high, moderate or low; and, (d) the quality of the design features and graphics in the app—rich, high quality or impoverished, poor quality. Using these dimensions, researchers rated the apps on a three-level scale: Levels I, II, and III. Few apps were classified as Level III apps on selected dimensions. This evaluation instrument guides teachers when selecting apps. As well, the evaluation instrument guides developers in going beyond apps that are overly prescriptive, that focus on quizzes, that are text based, and include only surface aspects of using multi-modality in learning, to apps that are more aligned with emergent curricula, that focus also on conceptual understanding, and that utilize multiple, interactive representations of mathematics concepts

GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.</p

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Association of genetic polymorphisms of bFGF, CRABP-I, PDGFRB and TGF-beta1 with the etiopathogenesis of Moyamoya

Die Moyamoya-Krankheit (Engl.: Moyamoya Disease, kurz: MMD) ist eine chronische zerebrovaskuläre Krankheit, für welche bislang keine kurative Therapie existiert. Dies ist unter anderem darauf zurückzuführen, dass Ätiologie und Pathogenese von Moyamoya noch weitgehend ungeklärt sind. Bezüglich der Ätiologie scheint eine genetische Ursache wahrscheinlich und an der Pathogenese scheint eine (Mit-)Beteiligung von diversen Zytokinen wahrscheinlich, welche bei Moyamoya-Patienten im Vergleich zu gesunden Kontrollpersonen als verändert exprimiert nachgewiesen wurden. Ziel dieser Studie war es, Polymorphismen im genetischen Bereich von verändert exprimierten Zytokine bzw. deren Rezeptoren bei Moyamoya-Patienten aufzudecken und somit Hinweise auf eine mögliche Korrelation zwischen diesen genetischen Variationen und der Ätiopathogenese von Moyamoya zu erhalten. In unserer Studie untersuchten wir dreizehn Einzelnukleotid-Polymorphismen, sogenannte „Single Nucleotide Polymorphisms“, auf Differenzen zwischen einer Fallgruppe mit Moyamoya-Patienten und einer gesunden Kontrollgruppe durch Sequenzierung entsprechender Genregionen. Die hierfür benötigte DNS extrahierten wir aus Blutproben von 41 betroffenen Patienten und 68 gesunden Kontrollpersonen aus dem europäischen Raum. Die untersuchten Einzelnukleotid-Polymorphismen liegen in den genetischen Regionen von bFGF (basic fibroblast growth factor), CRABP1 (cellular retinoic acid-binding protein 1), PDGFRB (platelet derived growth factor receptor beta), und TGFB1 (transforming growth factor beta 1), welche von uns auf Grund ausführlicher Literaturrecherchen als mögliche relevante Faktoren bei der Ätiopathogenese von Moyamoya eingestuft wurden. Als Ergebnis wiesen drei SNPs in den genetischen Bereichen von PDGFR und TGF-beta1 positive Ergebnisse auf bzgl. einer Korrelation zwischen Polymorphismus und Vorhandensein von Moyamoya. Dies könnte somit hinweisend sein für eine genetische Beteiligung dieser Faktoren an der Ätiopathogenese von Moyamoya und ein Baustein für das Auffinden einer zukünftigen Heilungsmöglichkeit sein.Moyamoya Disease (MMD) is a cerebrovascular disease whose etiology is still widely unknown. However, a genetic background seems to be probable. Several publications on Moyamoya describe differences of cytokine and growth factor concentrations in different specimen, as for example basic fibroblast growth factor (BFGF), cellular retinoic acid-binding protein 1 (CRABP1), platelet derived growth factor receptor beta (PDGFRB), and transforming growth factor beta 1 (TGFB1). These factors are, for example, involved in vascular growth and transformation processes. In our study we analyzed the DNA of patients with MMD for single nucleotide polymorphisms (SNPs) in and upstream of the genes of these factors. Altogether thirteen SNPs were genotyped with custom made primers, comparing 41 DNA samples of MMD patients to 68 healthy controls from central Europe. We found positive association of two SNPs in the genetic region of PDGFRB and of one located in the genetic region of TGFB1, what suggests that these two factors may play a role in the development of MMD

Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2, in patients with advanced solid tumors

Background M4112 is an oral, potent, and selective indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) dual inhibitor. Here, we report preclinical data and first-in-human phase I data, including safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy, of M4112 monotherapy in patients with advanced solid tumors.Methods In preclinical studies, M4112 was administered to mice with IDO1-expressing tumors to determine tumor IDO1 and liver TDO2 inhibition. In the phase I trial, patients received doses of M4112 two times per day in 28-day cycles until progression, toxicity, or withdrawal of consent. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). The primary endpoint was the incidence of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and treatment-emergent changes in safety parameters. Other endpoints included pharmacokinetics, pharmacodynamics, and antitumor effects.Results In mice, M4112 significantly decreased the kynurenine:tryptophan ratio in the liver and tumor. Fifteen patients received M4112 at five distinct dose levels (three patients per cohort: 100, 200, 400, 600, and 800 mg two times per day orally). Initially, all doses inhibited IDO1 ex vivo, but plasma kynurenine levels returned to or exceeded baseline levels after day 15. Despite initial changes in kynurenine, there was no significant reduction of plasma kynurenine at steady state. There was one DLT (grade 3 allergic dermatitis; 800 mg two times per day) and one grade 2 QT prolongation (800 mg two times per day), resulting in dose reduction (not a DLT). M4112 was well tolerated, and neither the MTD nor the RP2D was established. TEAEs included fatigue, nausea, and vomiting. The best overall response was stable disease (n=9, 60%).Conclusions There were no serious safety concerns at any dose. Although M4112 inhibited IDO1 activity ex vivo, plasma kynurenine levels were not reduced despite achieving target exposure.Trial registration number NCT03306420

Youth Self-Harm and the Role of Reasons for Living and Hope: A Secondary Analysis from a Randomized Controlled Trial

Self-harm (SH) is one of the strongest predictors of eventual death by suicide. This study examines the potential protective role of reasons for living (RFL) and hope in youth with a history of self-harm using data from a randomized control trial (RCT) of brief cognitive behavioural therapy (BCBT). A single-blind, pilot RCT examined the efficacy of BCBT for suicide prevention versus an attentional control in youth aged 15-25 admitted to hospital following self-harm. Subjects’ reasons for living and hope were measured weekly by the Reasons for Living Scale (RFL) and Adult Hope Scale (AHS), respectively, for 10 weeks of acute treatment. Logistic regression was performed to evaluate whether baseline RFL and AHS scores predicted repeat self-harm. Mann-Whitney U tests were used to compare median RFL and AHS scores. Our study did not find associations between reasons for living or hope and repeat self-harm in youth. Treatment with BCBT was also not associated with improved scores on either measure

Youth self-harm and the role of reasons for living and hope: A secondary analysis from a randomized controlled trial

Self-harm (SH) is one of the strongest predictors of eventual death by suicide. This study examines the potential protective role of reasons for living (RFL) and hope in youth with a history of self-harm using data from a randomized control trial (RCT) of brief cognitive behavioural therapy (BCBT). A single-blind, pilot RCT examined the efficacy of BCBT for suicide prevention versus an attentional control in youth aged 15-25 admitted to hospital following self-harm. Subjects’ reasons for living and hope were measured weekly by the Reasons for Living Scale (RFL) and Adult Hope Scale (AHS), respectively, for 10 weeks of acute treatment. Logistic regression was performed to evaluate whether baseline RFL and AHS scores predicted repeat self-harm. Mann-Whitney U tests were used to compare median RFL and AHS scores. Our study did not find associations between reasons for living or hope and repeat self-harm in youth. Treatment with BCBT was also not associated with improved scores on either measure

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