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Introduction: Mechanisms for liraglutide-induced weight loss are poorly understood. Objective: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals. Design: Participants ( N =49, 18–75 years, body mass index: 30–40 kg m −2 ) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed. Results: Five-hour gastric emptying (AUC 0–300 min ) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80–1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg ( P =0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg ( P =0.14). Both liraglutide doses similarly reduced fasting glucose (0.5–0.6 mmol l −1 versus placebo, P <0.0001), glucose C max and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC 0–300 min (by ∼26% versus placebo, P =0.02). Glucagon iAUC 0–300 min decreased by ∼30%, and iAUC 0–60 min for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk. Conclusion: Gastric emptying AUC 0–300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

In their review (low-glycaemic index diets and body weight regulation (2006)), McMillan-Price and Brand-Miller argue that the low glycemic index (GI) diet is a simple and more popular diet that will successfully improve cardiovascular risk factors and reduce body weight. We do not find that there is convincing evidence in the existing literature to suggest that a low GI diet is superior in achieving improvement in cardiovascular health and in reducing body weight in healthy overweight subjects, when compared to official dietary advice recommending a diet high in vegetables, fruit and fiber, and low in sugar and fat. This lack of evidence might partly be due to the lack of long-term, well-powered studies, with well-controlled diets differing only in GI. Data also suggest that subjects’ insulin sensitivity might be an important predictor of the effects of a low GI diet, and therefore findings from studies in insulin-resistant and diabetic subjects should not be extrapolated to findings in healthy individuals. We agree with McMillan-Price and Brand-Miller when they state that ‘in practice it is difficult to tease out the separate effects of GI, palatability, volume, fiber and other factors that influence satiety responses to realistic meals’. Predicting GI of realistic meals has also proven difficult. We therefore find that future studies should focus on individual food factors, such as the effect of whole grain, including intact grains, fiber, including resistant starch, energy density and preparation methods. This approach would allow for more tightly controlled trials, with less confounding factors, and also lead to simpler dietary advice with assured efficacy.

Abstract Background To investigate the distribution of urine isolates and antibiotic resistance patterns in the predominant uropathogen Escherichia coli in migrant and non-migrant individuals. Methods We linked a cohort consisting of all migrants obtaining residence as refugees or family-reunited migrants in Denmark between January 1993 and December 2015 to hospital urine samples examined from January 2000 to December 2015 at the Department of Microbiology, University Hospital Hvidovre, Denmark. Samples from non-migrant individuals, Danish-born from Danish parents, were included as comparison. Analysis was carried out using multivariate logistic regression. Results There were 14 561 first-time urine samples included, with E. coli being the most prevalent bacterial pathogen. Of the identified isolates, 4686/11 737 were E. coli among non-migrants and 1032/2824 among migrants. Sulfamethoxazol–Trimethoprim (SXT) resistance was found in 34.3% (350/1020) of E. coli isolates among migrants and 23.2% (1070/4619) among non-migrant patients [odds ratio (OR) 1.73, 95% confidence interval (CI): 1.47–2.03]. Ciprofloxacin resistance was found in 5.8% (36/618) of isolates among migrants and 2.2% (67/3092) among non-migrants (OR 2.20, 95% CI: 1.37–3.53). Gentamicin (GEN) resistance was seen in 10.8% (61/565) and 4.7% (110/2328) of isolates (OR 2.33, 95% CI:1.63–3.34), Cefuroxime resistance in 8.5% (87/1019) and 3.4% (158/4618) (OR 2.40, 95% CI:1.77–3.24), Ampicillin (AMP) resistance in 51.4% and 40.8% (OR 1.65, 95% CI: 1.42–1.92) and Piperacillin–Tazobactam resistance in 6.9% (30/432) and 4.2% (65/1532) for migrant and non-migrant patients, respectively. When stratifying according to migrant status, family-reunited had higher odds of resistance than refugees for SXT, GEN and AMP. Conclusions Prevalence of antibiotic resistance was significantly higher in E. coli isolates among migrants, both refugees and family-reunited, than non-migrant patients. Differences could not be explained by comorbidity or income. The results emphasize the importance of urine sample testing in both local-born and migrants before antibiotic start-up and point to the benefit of considering migration to secure individual treatment and equal health outcomes.

We aimed to test the effects of three different weight maintenance diets on appetite, glucose and fat metabolism following an initial low-energy diet (LED) induced body weight loss. Following an 8-week LED and a 2–3-week refeeding period, 131 subjects were randomized to three diets for 6 months: MUFA, moderate-fat (35–45 energy percentage (E%) fat), high in MUFA with low glycaemic index; LF, low fat (20–30 E% fat) or CTR, control (35 E% fat). A meal test study was performed in a subgroup, before and after the 6-month dietary intervention, with forty-two subjects completing both meal tests. No difference in body weight, energy intake or appetite ratings were observed between diets. Both the LF and MUFA diets compared to CTR diet reduced postprandial glycaemia and insulinaemia and lowered fasting insulin from month 0 to month 6. Following the 8-week LED period lower levels of the appetite regulating peptides, pancreatic polypeptide, peptide YY, glucagon-like peptide-1 and glucagon-like peptide-2, along with increased appetite scores were seen in comparison to measurements performed after the 6-month dietary intervention. In conclusion, the two competing diets, MUFA and LF, were equally good with respect to glucose metabolism, whereas the CTR diet resembling the typical Western diet, high in SFA, sugar and high glycaemic carbohydrates, indicated associations to lowering of insulin sensitivity. Lower levels of appetite regulatory peptides along with increased appetite scores following an 8-week LED and 2–3-week refeeding period, suggest that strategies for physiological appetite control following a LED period are needed, in order to prevent weight regain.

BackgroundSimulation-based surgical training (SBST) is key to securing future surgical expertise. Proficiency-based training (PBT) in laparoscopy has shown promising results on skills transfer. However, time constraints and limited possibilities for distributed training constitute barriers to effective PBT. Home-based training may provide a solution to these barriers and may be a feasible alternative to centralized training in times of assembly constraints.MethodsWe randomly assigned first-year trainees in abdominal surgery, gynecology, and urology to either centralized instructor-regulated training (CIRT) or home-based self-regulated training (HSRT) in laparoscopy. All participants trained on portable box trainers providing feedback on metrics and possibility for video reviewing. Training in both groups was structured as PBT with graded proficiency exercises adopted from the Fundamentals of Laparoscopic Surgery (FLS). The HSRT group trained at home guided by online learning materials, while the CIRT group attended two training sessions in the simulation center with feedback from experienced instructors. Performance tests consisted of hand–eye and bimanual coordination, suture and knot-tying, and FLS exercises. We analyzed passing rates, training time and distribution, and test performances.ResultsPassing rates were 87% and 96% in the CIRT and HSRT group, respectively. HSRT facilitated distributed training and resulted in greater variation in training times. Task times for hand–eye and bimanual coordination were significantly reduced between pretest and posttest in both groups. Trainees maintained their posttest performances at the 6-month retention test. Our analyses revealed no significant inter-group differences in performances at pretest, posttest, or retention test. Performance improvements in the two groups followed similar patterns.ConclusionCIRT and HSRT in laparoscopy result in comparable performance improvements. HSRT in laparoscopy is a feasible and effective alternative to CIRT when offered inside a supportive instructional design. Further research is needed to clarify trainees’ preferences and explore facilitators and barriers to HSRT.

We formulate an evolutionary learning process with trembles for static games of incomplete information. For many games, if the amount of trembling is small, play will be in accordance with the games' (strict) Bayesian equilibria most of the time. This supports the notion of Bayesian equilibrium. Often the process will select a specific equilibrium. We study an extension to incomplete information of the prototype conflict known as \"Chicken\" and find that the equilibrium selection by evolutionary learning may well be in favor of inefficient Bayesian equilibria where some types of players fail to coordinate.

The Choquet integral is an integral part of recent advances in decision theory involving non-additive measures. In this article we present two new axiomatic characterizations of this functional.

This paper studies adaptive learning in extensive form games and provides conditions for convergence points of adaptive learning to be sequential equilibria. Precisely, we present a set of conditions on learning sequences such that an assessment is a sequential equilibrium if and only if there is a learning sequence fulfilling the conditions, which leads to the assessment.