A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

The effect of clinical experience, judgment task difficulty and time pressure on nurses’ confidence calibration in a high fidelity clinical simulation

Background: Misplaced or poorly calibrated confidence in healthcare professionals’ judgments compromises the quality of health care. Using higher fidelity clinical simulations to elicit clinicians’ confidence 'calibration' (i.e. overconfidence or underconfidence) in more realistic settings is a promising but underutilized tactic. In this study we examine nurses’ calibration of confidence with judgment accuracy for critical event risk assessment judgments in a high fidelity simulated clinical environment. The study also explores the effects of clinical experience, task difficulty and time pressure on the relationship between confidence and accuracy. Methods: 63 student and 34 experienced nurses made dichotomous risk assessments on 25 scenarios simulated in a high fidelity clinical environment. Each nurse also assigned a score (0–100) reflecting the level of confidence in their judgments. Scenarios were derived from real patient cases and classified as easy or difficult judgment tasks. Nurses made half of their judgments under time pressure. Confidence calibration statistics were calculated and calibration curves generated. Results: Nurse students were underconfident (mean over/underconfidence score −1.05) and experienced nurses overconfident (mean over/underconfidence score 6.56), P = 0.01. No significant differences in calibration and resolution were found between the two groups (P = 0.80 and P = 0.51, respectively). There was a significant interaction between time pressure and task difficulty on confidence (P = 0.008); time pressure increased confidence in easy cases but reduced confidence in difficult cases. Time pressure had no effect on confidence or accuracy. Judgment task difficulty impacted significantly on nurses’ judgmental accuracy and confidence. A 'hard-easy' effect was observed: nurses were overconfident in difficult judgments and underconfident in easy judgments. Conclusion: Nurses were poorly calibrated when making risk assessment judgments in a high fidelity simulated setting. Nurses with more experience tended toward overconfidence. Whilst time pressure had little effect on calibration, nurses’ over/underconfidence varied significantly with the degree of task difficulty. More research is required to identify strategies to minimize such cognitive biases

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Meta-metakognition : The regulation of confidence realism in episodic and semantic memory

The aim of this thesis was to investigate whether people have the ability to make their confidence judgments for episodic and semantic memory tasks more realistic. How realistic a person’s confidence judgments are reflects how well their confidence judgments for their memory reports correspond to the actual correctness of the reports. The regulation of first-order confidence judgments by making successful second-order judgments can be seen as a form of meta-metacognition, since it aims at regulating a metacognitive process. Study I consisted of two experiments, and investigated whether people could increase the realism in their reports by excluding the confidence judgments they believed were unrealistic. The participants were shown a video clip and, in the Confidence task, were told to answer questions about the video and rate how confident they were that they had answered the questions correctly. Half of the participants answered two-alternative questions (recognition), and half had to come up with their own answers (recall). The participants then performed the Exclusion task, in which they were asked to exclude the 15 answers they believed had the most unrealistic confidence judgments. In Experiment 1 the recognition condition decreased their level of realism in their report, and in Experiment 2 the recall condition increased their level of realism. In Study II, the aim was to investigate whether people could increase the realism in their report by modifying the confidence judgments they believed were unrealistic. The relationship between realism of confidence and two possible memory cues, the phenomenological memory qualities Remember/Know and processing fluency, was investigated as well. The procedure was similar to that in Study I, with the exception that all participants answered recall questions and that the participants in the so-called Adjustment task were told to modify the confidence judgments they believed were unrealistic. Results showed that the participants were able to increase the realism of their confidence judgments, even though the effect was small. In Study III, the aim was to investigate whether people had the possibility to increase their confidence realism in semantic memory reports and whether individual differences, personality and cognitive styles, could help explain differences in this ability. The procedure was very similar to that in Study II, and the results showed that the participants only managed to increase the realism for correct items in the Adjustment task. In Study IV, the aim was to investigate whether the improvements in realism found in Study II could be further enhanced by giving people advice during the Adjustment task and asking them to “try more” in an Extra Adjustment task. However, results showed that although the participants managed to improve their realism like in Study II, they were not able to further improve it when given advice or by “trying more”. In all, Studies II, III and IV (and to some extent also Study I) lend support to the idea that people are able to regulate the realism of their confidence judgments by making successful second-order judgments