How feedback boosts motivation and play in a brain-training game

AbstractGames are important vehicles for learning and behavior change as long as players are motivated to continue playing. We study the impact of verbal feedback in stimulating player motivation and future play in a brain-training game. We conducted a 2 (feedback valence: positive vs. negative)×3 (feedback type: descriptive, comparative, evaluative) between-subjects experiment (N=157, 69.4% female, Mage=32.07). After playing a brain-training game and receiving feedback, we tapped players’ need satisfaction, motivation and intention to play the game again. Results demonstrate that evaluative feedback increases, while comparative feedback decreases future game play. Furthermore, negative feedback decreases players’ feeling of competence, but also increases immediate game play. Positive feedback, in contrast, satisfies competence and autonomy needs, thereby boosting intrinsic motivation. Negative feedback thus motivates players to repair poor short-term performances, while positive feedback is more powerful in fostering long-term motivation and play

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

Contains fulltext : 88175.pdf (publisher's version ) (Open Access)We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping

Rational design of FRET-based sensor proteins

Real-time imaging of molecular events inside living cells is important for understanding the basis of physiological processes and diseases. Genetically encoded sensors that use fluorescence resonance energy transfer (FRET) between two fluorescent proteins are attractive in this respect because they do not require cell-invasive procedures, can be targeted to different locations in the cell and are easily adapted through mutagenesis and directed evolution approaches. Most FRET sensors developed so far show a relatively small difference in emission ratio upon activation, which severely limits their application in high throughput cell-based screening applications. In our work, we try to develop strategies that allow design of FRET-based sensors with intrinsically large ratiometric changes. This rational design approach requires a better understanding and quantitative description of the conformational changes in these fusion proteins. In this chapter, I first discuss some of the key factors and strategies that determine the ratiometric response of FRET sensors, followed by an overview of our recent work in this area. Important concepts that will be discussed are (1) the conformational behavior of flexible peptide linkers to quantitatively describe the dependence of energy transfer on linker length and (2) the control of intramolecular domain interactions using the concept of effective molecular concentration

Rational design of FRET-based sensor proteins

Real-time imaging of molecular events inside living cells is important for understanding the basis of physiological processes and diseases. Genetically encoded sensors that use fluorescence resonance energy transfer (FRET) between two fluorescent proteins are attractive in this respect because they do not require cell-invasive procedures, can be targeted to different locations in the cell and are easily adapted through mutagenesis and directed evolution approaches. Most FRET sensors developed so far show a relatively small difference in emission ratio upon activation, which severely limits their application in high throughput cell-based screening applications. In our work, we try to develop strategies that allow design of FRET-based sensors with intrinsically large ratiometric changes. This rational design approach requires a better understanding and quantitative description of the conformational changes in these fusion proteins. In this chapter, I first discuss some of the key factors and strategies that determine the ratiometric response of FRET sensors, followed by an overview of our recent work in this area. Important concepts that will be discussed are (1) the conformational behavior of flexible peptide linkers to quantitatively describe the dependence of energy transfer on linker length and (2) the control of intramolecular domain interactions using the concept of effective molecular concentration

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease