Outnumb3r3d : intrinsically motivating mathematics for the PlayStation 4

This paper and accompanying poster describes the design of an intrinsically integrated educational game to improve children’s competencies in mental mathematics. A number of researchers have suggested that educational games are more effective when they are closely integrated with their learning content. Specifically work by the lead author has showed that a closer integration between an educational game's core-mechanics and its learning content can be both more appealing (in terms of time spent on-task) and more educationally effective (in terms of learning outcomes) than a less integrated "edutainment" approach. However, cursory approaches to integrating learning content remain common in contemporary educational software, and the literature lacks an exemplar of what can be achieved using an integrated approach. The Outnumb3r3d game was conceived to provide a commercial and theoretical exemplar of intrinsic integration for the Nintendo Wii, but was never completed. This project is now porting the original Wii prototype onto the PlayStation 4 in order to revive Outnumb3r3d as a research project. This paper details the design of Outnumb3r3d with reference to the key theoretical constructs that underlie its pedagogical design. In doing so it provides an example of a game design created to integrate mathematical learning content seamlessly into the game's core mechanics, ensuring that the mathematics is what makes the game intrinsically motivating to play rather than trying to hide or "sugar coat" its learning content. At the time of writing the game’s implementation is still a “work in progress”, but is expected to be the subject of future empirical evaluations into its effectiveness as a teaching tool

Endogenous fantasy and learning in digital games.

Many people believe that educational games are effective because they motivate children to actively engage in a learning activity as part of playing the game. However, seminal work by Malone (1981), exploring the motivational aspects of digital games, concluded that the educational effectiveness of a digital game depends on the way in which learning content is integrated into the fantasy context of the game. In particular, he claimed that content which is intrinsically related to the fantasy will produce better learning than that which is merely extrinsically related. However, this distinction between intrinsic and extrinsic (or endogenous and exogenous) fantasy is a concept that has developed a confused standing over the following years. This paper will address this confusion by providing a review and critique of the empirical and theoretical foundations of endogenous fantasy, and its relevance to creating educational digital games. Substantial concerns are raised about the empirical basis of this work and a theoretical critique of endogenous fantasy is offered, concluding that endogenous fantasy is a misnomer, in so far as the "integral and continuing relationship" of fantasy cannot be justified as a critical means of improving the effectiveness of educational digital games. An alternative perspective on the intrinsic integration of learning content is described, incorporating game mechanics, flow and representations

BVRIJK light curves and radial velocity curves for selected Magellanic Cloud Cepheids

We present high precision and well sampled BVRIJK light curves and radial velocity curves for a sample of five Cepheids in the SMC. In addition we present radial velocity curves for three Cepheids in the LMC. The low metallicity (Fe/H ~ -0.7) SMC stars have been selected for use in a Baade-Wesselink type analysis to constrain the metallicity effect on the Cepheid Period-Luminosity relation. The stars have periods of around 15 days so they are similar to the Cepheids observed by the Extragalactic Distance Scale Key Project on the Hubble Space Telescope. We show that the stars are representative of the SMC Cepheid population at that period and thus will provide a good sample for the proposed analysis. The actual Baade-Wesselink analysis are presented in a companion paper.Comment: Accepted for publication in A&A, 23 pages, 10 figures, data tables will be made available electronically from the CD

Thermal Behavior of Benzoic Acid/Isonicotinamide Binary Cocrystals

YesA comprehensive study of the thermal behavior of the 1:1 and 2:1 benzoic acid/isonicotinamide cocrystals is reported. The 1:1 material shows a simple unit cell expansion followed by melting upon heating. The 2:1 crystal exhibits more complex behavior. Its unit cell first expands upon heating, as a result of C–H···π interactions being lengthened. It then is converted into the 1:1 crystal, as demonstrated by significant changes in its X-ray diffraction pattern. The loss of 1 equiv of benzoic acid is confirmed by thermogravimetric analysis–mass spectrometry. Hot stage microscopy confirms that, as intuitively expected, the transformation begins at the crystal surface. The temperature at which conversion occurs is highly dependent on the sample mass and geometry, being reduced when the sample is under a gas flow or has a greater exposed surface area but increased when the heating rate is elevated

Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations: a case-control and observational cohort study

Summary Background Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department. Methods Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities. Findings A three-gene transcript signature, comprising HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0·976 (95% CI 0·919−1·000), sensitivity of 97·3% (85·8−99·9), and specificity of 100% (63·1−100). The AUROC for C-reactive protein (CRP) was 0·833 (0·694−0·944) and for leukocyte count was 0·938 (0·840−0·986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte count for discriminating viral infections from all other infections. In the second validation analysis, which included SARS-CoV-2-positive participants, the signature discriminated 35 bacterial infections from 34 SARS-CoV-2-positive COVID-19 infections with AUROC of 0·953 (0·893−0·992), sensitivity 88·6%, and specificity of 94·1%. Interpretation This novel three-gene signature discriminates viral infections, including COVID-19, from other emergency infection presentations in adults, outperforming both leukocyte count and CRP, thus potentially providing substantial clinical utility in managing acute presentations with infection. Funding National Institute for Health Research, Medical Research Council, Wellcome Trust, and EU-FP7

A Chemical Analog of Curcumin as an Improved Inhibitor of Amyloid Abeta Oligomerization

Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6-7-fold over that measured for curcumin

Diagnosis of childhood febrile illness using a multi-class blood RNA molecular signature

Background: Appropriate treatment and management of children presenting with fever depend on accurate and timely diagnosis, but current diagnostic tests lack sensitivity and specificity and are frequently too slow to inform initial treatment. As an alternative to pathogen detection, host gene expression signatures in blood have shown promise in discriminating several infectious and inflammatory diseases in a dichotomous manner. However, differential diagnosis requires simultaneous consideration of multiple diseases. Here, we show that diverse infectious and inflammatory diseases can be discriminated by the expression levels of a single panel of genes in blood. Methods: A multi-class supervised machine-learning approach, incorporating clinical consequence of misdiagnosis as a ‘‘cost’’ weighting, was applied to a whole-blood transcriptomic microarray dataset, incorporating 12 publicly available datasets, including 1,212 children with 18 infectious or inflammatory diseases. The transcriptional panel identifiedwas further validated in a new RNA sequencing dataset comprising 411 febrile children. Findings: We identified 161 transcripts that classified patients into 18 disease categories, reflecting individual causative pathogen and specific disease, as well as reliable prediction of broad classes comprising bacterial infection, viral infection, malaria, tuberculosis, or inflammatory disease. The transcriptional panel was validated in an independent cohort andbenchmarked against existingdichotomousRNA signatures. Conclusions: Our data suggest that classification of febrile illness can be achieved with a single blood sample and opens the way for a new approach for clinical diagnosis. Funding: European Union’s Seventh Framework no. 279185; Horizon2020 no. 668303 PERFORM; Wellcome Trust (206508/Z/17/Z); Medical Research Foundation (MRF-160-0008-ELP-KAFO-C0801); NIHR Imperial BRC