A novel approach and software component for supporting competence-based learning with serious games

Digital educational games constitute a major opportunity for acquiring knowledge and competences in a different way than traditional classroom- and technology-based methods. This paper presents a novel approach for a game component that structures the game play in an adaptive way. This approach consists of a combination of three learning theories and techniques. First, Competence-based Knowledge Space Theory is used structure a knowledge domain into competences and game situations. Second, the Leitner system of flashcards is used to establish structured and timed repetition of competences to be acquired. Third, the Ebbinghaus forgetting curve is taken into account to model forgetting learned competences. This approach has been implemented as a game component in line with the games component architecture of the RAGE project. The design and development of this component followed the requirements of the French games company Kiupe that includes it in its environment of games and mini-games

Influence of human leukocyte antigen (HLA) alleles and killer cell immunoglobulin-like receptors (KIR) types on heparin-induced thrombocytopenia (HIT)

Objectives Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT.\ud Methods HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina® OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. P values for HLA and KIR association were corrected using a false discovery rate (FDR) q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Results Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81[1.57-5.02], p=2.1x10-4, q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). Conclusions The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary

Anomalously localized states and multifractal correlations of critical wavefunctions in two-dimensional electron systems with spin-orbital interactions

Anomalously localized states (ALS) at the critical point of the Anderson transition are studied for the SU(2) model belonging to the two-dimensional symplectic class. Giving a quantitative definition of ALS to clarify statistical properties of them, the system-size dependence of a probability to find ALS at criticality is presented. It is found that the probability increases with the system size and ALS exist with a finite probability even in an infinite critical system, though the typical critical states are kept to be multifractal. This fact implies that ALS should be eliminated from an ensemble of critical states when studying critical properties from distributions of critical quantities. As a demonstration of the effect of ALS to critical properties, we show that the distribution function of the correlation dimension of critical wavefunctions becomes a delta function in the thermodynamic limit only if ALS are eliminated.Comment: 7 pages, 6 figure

Implicit weight bias in children age 9 to 11 years

OBJECTIVES: Assess implicit weight bias in children 9 to 11 years old. METHODS: Implicit weight bias was measured in children ages 9 to 11 (N = 114) by using the Affect Misattribution Procedure. Participants were shown a test image of a child for 350 milliseconds followed by a meaningless fractal (200 milliseconds), and then they were asked to rate the fractal image as "good" or "bad." We used 9 image pairs matched on age, race, sex, and activity but differing by weight of the child. Implicit bias was the difference between positive ratings for fractals preceded by an image of a healthy-weight child and positive ratings for fractals preceded by an image of an overweight child. RESULTS: On average, 64% of fractals shown after pictures of healthy-weight children were rated as "good, " compared with 59% of those shown after pictures of overweight children, reflecting an overall implicit bias rate of 5.4% against overweight children (P < .001). Healthy-weight participants showed greater implicit bias than over-and underweight participants (7.9%, 1.4%, and 0.3% respectively; P = .049). CONCLUSIONS: Implicit bias toward overweight individuals is evident in children aged 9 to 11 years with a magnitude of implicit bias (5.4%) similar to that in studies of implicit racial bias among adults

Growing Environmental Activists: Developing Environmental Agency and Engagement Through Children’s Fiction.

We explore how story has the potential to encourage environmental engagement and a sense of agency provided that critical discussion takes place. We illuminate this with reference to the philosophies of John Macmurray on personal agency and social relations; of John Dewey on the primacy of experience for philosophy; and of Paul Ricoeur on hermeneutics, dialogue, dialectics and narrative. We view the use of fiction for environmental understanding as hermeneutic, a form of conceptualising place which interprets experience and perception. The four writers for young people discussed are Ernest Thompson Seton, Kenneth Grahame, Michelle Paver and Philip Pullman. We develop the concept of critical dialogue, and link this to Crick's demand for active democratic citizenship. We illustrate the educational potential for environmental discussions based on literature leading to deeper understanding of place and environment, encouraging the belief in young people that they can be and become agents for change. We develop from Zimbardo the key concept of heroic resister to encourage young people to overcome peer pressure. We conclude with a call to develop a greater awareness of the potential of fiction for learning, and for writers to produce more focused stories engaging with environmental responsibility and activism

Influence of product placement in children's movies on children's snack choices

Background Media exposure affects health, including obesity risk. Children's movies often contain food placements—frequently unhealthy foods. However, it is not known if these cues influence children's food choices or consumption after viewing. We explored whether children's snack choices or consumption differs based on: 1) recent exposure to movies with high versus low product placement of unhealthy foods; and 2) children's weight status. Methods Children ages 9–11 were assigned to watch a high (“Alvin and the Chipmunks,” n = 54) or low (“Stuart Little,” n = 60) product-placement movie. After viewing, participants selected a snack choice from each of five categories, several of which were specifically featured in “Alvin.” Uneaten snacks from each participant were weighed upon completion. Snack choice and amount consumed by movie were compared by t-tests, and differences in snack choices by movie were tested with logistic regression. Results Participants consumed an average of 800.8 kcal; mean kcal eaten did not vary by movie watched. Participants who watched the high product-placement movie had 3.1 times the odds (95% CI 1.3–7.2) of choosing cheese balls (most featured snack) compared to participants who watched the low product-placement movie. Children who were overweight or obese consumed a mean of 857 kcal (95% CI: 789–925) compared to 783 kcal (95% CI: 742–823, p = 0.09) for children who were underweight or healthy weight. Children's weight status did not significantly affect their choice of snack. Conclusions Branding and obesogenic messaging in children's movies influenced some choices that children made about snack foods immediately following viewing, especially food with greatest exposure time in the film, but did not affect total calories consumed. Future studies should examine how the accumulation of these messages affects children's long-term food choices

Color superconducting quark matter core in the third family of compact stars

We investigate first order phase transitions from $\beta$-equilibrated hadronic matter to color flavor locked quark matter in compact star interior. The hadronic phase including hyperons and Bose-Einstein condensate of $K^-$ mesons is described by the relativistic field theoretical model with density dependent meson-baryon couplings. The early appearance of hyperons and/or Bose-Einstein condensate of $K^-$ mesons delays the onset of phase transition to higher density. In the presence of hyperons and/or $K^-$ condensate, the overall equations of state become softer resulting in smaller maximum masses than the cases without hyperons and $K^-$ condensate. We find that the maximum mass neutron stars may contain a mixed phase core of hyperons, $K^-$ condensate and color superconducting quark matter. Depending on the parameter space, we also observe that there is a stable branch of superdense stars called the third family branch beyond the neutron star branch. Compact stars in the third family branch may contain pure color superconducting core and have radii smaller than those of the neutron star branch. Our results are compared with the recent observations on RX J185635-3754 and the recently measured mass-radius relationship by X-ray Multi Mirror-Newton Observatory.Comment: 24 pages, RevTex, 9 figures included; section II shortened, section III elaborated, two new curves in Fig. 9 and acknowledgements added; version to bepublished in Phys. Rev.

Repetitive noninvasive monitoring of hsvl-tk-expressing t cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) has been successfully used to treat patients with different types of cancer. However, the long-term spatial-temporal dynamics of the distribution of systemically infused CTLs rlargely unknown. Noninvasive imaging of adoptively transferred CTLs using molecular-genetic reporter imaging with positron emission tomography and computed tomography (PET-CT) represents an innovative approach to understanding the long-term migratory patterns and therapeutic potential of adoptively transferred T cells. Here we report the application of repetitive PET-CT imaging with [18F]fluoro-5-ethyl-1-beta-D- arabinofuranosyluracil (18F-FEAU) in two nonhuman primates demonstrating that autologous polyclonal macaque T lymphocytes activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase (sr39HSV1-tk) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in sites of inflammation. This study represents a proof of principle and supports the application of 18F-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans

Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ null mice

Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30-minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL)-2Rγ null (NSG) mice. By isolating fucosylated and nonfucosylated CD34 + cells from CB, we showed that only fucosylated CD34 + cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34 + cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34 + cells, we hypothesized that increasing the proportion of CD34 + cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase-VI significantly increases the levels of CD34 + fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells or pattern of long-term, multilineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation