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Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR‐associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug‐eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point‐of‐care assay. Cox multivariable analysis was used to assess whether HPR‐associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin‐treated diabetes mellitus (ITDM), non–ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2‐year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non–insulin‐treated diabetes mellitus versus ITDM for 2‐year MACE (adjusted hazard ratio [HR] for non–ITDM, 2.28 [95% CI, 1.39–3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70–1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower‐risk non–ITDM patients than in higher‐risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents).

This expository article explores the connection between the polar duality from polyhedral geometry and mirror symmetry from mathematical physics and algebraic geometry. Topics discussed include duality of polytopes and cones as well as the famous quintic threefold and the toric variety of a reflexive polytope.

Introduction: Dietary guidelines worldwide emphasize the importance of consuming vegetables as part of a healthy diet. Despite this, translating this information into messages for consumers that change behavior has been difficult. There have been population-level social marketing campaigns as well as several smaller campaigns directed specifically toward children, which have demonstrated small increases in consumption. However, achieving meaningful and sustained increases in children's vegetable consumption remains a challenge. This article describes the process of synthesizing the published literature and translating these findings to inform the development of 7 best practice guidelines to increase children's vegetable intake. Methods: The first step in this process was a systematic review of scientific literature to identify the components of interventions that were associated with successfully increasing vegetable intake. The synthesis of effective intervention components was guided by the Behavior Change Wheel. These scientific findings were translated to guidelines for best practice. This process involved a team of nutrition and behavioral researchers and nutrition practitioners translating the science into actionable advice that could be adopted by a range of stakeholders. The 6 selected stakeholders included long daycare centers, after-hours school care providers, primary schools, industry groups and growers, researchers, and government policy makers. Stakeholders were involved in the development process through surveys and interviews to understand their requirements for resources to support adoption of the best practice guidelines within each setting and within the context of existing practice. Results: The guidelines center on coordination of effort, with a focus on components such as planning, environmental restructuring, barrier reduction, feedback, and monitoring. In consultation with key stakeholders, a range of resources were developed for each setting to support the implementation of best practice, with the aim of achieving meaningful increases in intake. The resources and tools have been made available at http://www.vegkit.com.au. Conclusions: The translation of knowledge into practice is not traditionally included as part of the research process. Therefore, combining the process of reviewing the science and translating the evidence to stakeholder resources to influence practice in 1 research study is novel, and the study could be used to guide future research translation activities within and beyond the field of public health nutrition.

Abstract Objective: To evaluate the impact of a menu box delivery service tailored to the long-day care (LDC) setting on improving menu compliance with recommendations, children’s diet quality and dietary intake while in care. Design: A cluster randomised controlled trial in LDC centres randomly assigned to an intervention (menu box delivery) or comparison (menu planning training) group. The primary outcome was child food provision and dietary intake. Secondary outcomes include menu compliance and process evaluation, including acceptability, fidelity and menu cost (per child, per day). Setting: South Australian LDC centres. Participants: Eight LDC centres (n 224 children) provided data. Results: No differences were observed in serves/d between intervention and comparison centres, for provision (intervention, 0·9 inter-quartile range (IQR) 0·7–1·2; comparison, 0·8 IQR 0·5–1·3) or consumption (intervention, 0·5 IQR 0·2–0·8; comparison, 0·5 IQR 0·3–0·9) of vegetables. Child food provision and dietary intake were similar across both groups for all food groups (P < 0·05). At follow-up, all intervention centres met menu planning guidelines for vegetables, whereas only one comparison centre met guidelines. Intervention centre directors found the menu box delivery more acceptable than cooks. Cost of the intervention was AUD$2·34 greater than comparison centres (intervention, AUD$4·62 (95 % CI ($4·58, $4·67)); comparison, AUD$2·28 (95 % CI ($2·27, $2·30)) per child, per day). Conclusions: Menu compliance can be improved via a menu delivery service, delivering equivalent impacts on child food provision and dietary intake compared with an online training programme. Further exploration of cooks acceptability and cost is essential before scaling up to implementation.

Abstract Objective: To inform a package of initiatives to increase children’s vegetable intake while in long day care (LDC) by evaluating the independent and combined effects of three initiatives targeting food provision, the mealtime environment and the curriculum. Design: Using the Multiphase Optimisation Strategy (MOST) framework, a 12-week, eight-condition (n 7 intervention, n 1 control) randomised factorial experiment was conducted. Children’s dietary intake data were measured pre- and post-initiative implementation using the weighed plate waste method (1× meal and 2× between-meal snacks). Vegetable intake (g/d) was calculated from vegetable provision and waste. The optimal combination of initiatives was determined using a linear mixed-effects model comparing between-group vegetable intake at follow-up, while considering initiative fidelity and acceptability. Setting: LDC centres in metropolitan Adelaide, South Australia. Participants: 32 centres, 276 staff and 1039 children aged 2–5 years. Results: There were no statistically significant differences between any of the intervention groups and the control group for vegetable intake (all P > 0·05). The curriculum with mealtime environment group consumed 26·7 g more vegetables/child/day than control (ratio of geometric mean 3·29 (95 % CI 0·96, 11·27), P = 0·06). Completion rates for the curriculum (> 93 %) and mealtime environment (61 %) initiatives were high, and acceptability was good (4/5 would recommend), compared with the food provision initiative (0–50 % completed the menu assessment, 3/5 would recommend). Conclusion: A programme targeting the curriculum and mealtime environment in LDC may be useful to increase children’s vegetable intake. Determining the effectiveness of this optimised package in a randomised controlled trial is required, as per the evaluation phase of the MOST framework.

Children need to be repeatedly and consistently exposed to a variety of vegetables from an early age to achieve an increase in vegetable intake. A focus on enjoyment and learning to like eating vegetables at an early age is critical to forming favourable lifelong eating habits. Coordinated work is needed to ensure vegetables are available and promoted in a range of settings, using evidence-based initiatives, to create an environment that will support children’s acceptance of vegetables. This will help to facilitate increased intake and ultimately realise the associated health benefits. The challenges and evidence base for a new approach are described.

Summary: Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome.

Abstract Objective: To determine the reach, adoption, implementation and effectiveness of an intervention to increase children’s vegetable intake in long day care (LDC). Design: A 12-week pragmatic cluster randomised controlled trial, informed by the multiphase optimisation strategy (MOST), targeting the mealtime environment and curriculum. Children’s vegetable intake and variety was measured at follow-up using a modified Short Food Survey for early childhood education and care and analysed using a two-part mixed model for non-vegetable and vegetable consumers. Outcome measures were based on the RE-AIM framework. Setting: Australian LDC centres. Participants: Thirty-nine centres, 120 educators and 719 children at follow-up. Results: There was no difference between intervention and waitlist control groups in the likelihood of consuming any vegetables when compared with non-vegetable consumers for intake (OR = 0·70, (95 % CI 0·34–1·43), P = 0·32) or variety (OR = 0·73 (95 % CI 0·40–1·32), P = 0·29). Among vegetable consumers (n 652), there was no difference between groups in vegetable variety (exp(b): 1·07 (95 % CI:0·88–1·32, P = 0·49) or vegetable intake (exp(b): 1·06 (95 % CI: 0·78, 1·43)), P = 0·71) with an average of 1·51 (95 % CI 1·20–1·82) and 1·40 (95 % CI 1·08–1·72) serves of vegetables per day in the intervention and control group, respectively. Intervention educators reported higher skills for promoting vegetables at mealtimes, and knowledge and skills for teaching the curriculum, than control (all P < 0·001). Intervention fidelity was moderate (n 16/20 and n 15/16 centres used the Mealtime environment and Curriculum, respectively) with good acceptability among educators. The intervention reached 307/8556 centres nationally and was adopted by 22 % eligible centres. Conclusions: The pragmatic self-delivered online intervention positively impacted educator’s knowledge and skills and was considered acceptable and feasible. Intervention adaptations, using the MOST cyclic approach, could improve intervention impact on children’ vegetable intake.

Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change; however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

Abstract Background The TROIKA trial established that HD201 and trastuzumab were equivalent in terms of primary endpoints (total pathological complete response) following neoadjuvant treatment. The objective of the present analysis was to compare survival outcomes and final safety. Methods In the TROIKA trial, patients with ERBB2-positive early breast cancer were randomized and treated with either HD201 or the referent trastuzumab. Eligible patients received 8 cycles of either HD201 or referent trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in combination with 8 cycles of chemotherapy (4 cycles of docetaxel, 75 mg/m2, followed by 4 cycles of epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) in the neoadjuvant setting. The patients then underwent surgery followed by 10 cycles of adjuvant HD201 or referent trastuzumab according to their initial randomization to complete one year of trastuzumab-directed therapy. Event-free and overall survival rates were calculated using Kaplan–Meier analysis. The hazard ratio for event-free survival was estimated by Cox proportional hazards regression. Results The final analysis was performed after all patients completed the study at a median follow-up of 37.7 months (Q1-Q3, 37.3–38.1 months). A total of 502 randomized patients received either HD201 or the referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. In this population, the 3-year event-free survival rates were 85.6% (95% CI: 80.28–89.52) and 84.9% (95% CI: 79.54–88.88) in the HD201 and referent trastuzumab groups, respectively (log rank p = 0.938) (HR 1.02, 95% CI: 0.63–1.63; p = 0.945). The 3-year overall survival rates were comparable between the HD201 (95.6%; 95% CI: 91.90–97.59) and referent trastuzumab treatment groups (96.0%, 95% CI: 92.45–97.90) (log rank p = 0.606). During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively. Serious adverse events were rare and none of which were related to the study treatment. Conclusions This final analysis of the TROIKA trial further confirms the comparable efficacy and safety of HD201 and trastuzumab. Trial registration ClinicalTrials.gov identifier: NCT03013504.

The Ocean Cleanup introduces a Digital Twin (DT) describing the cleanup systems made of netting to extract marine litter from our oceans. It consists of two wings forming a “U-shape” and a retention zone. During operation, the system is towed and drag-driven with a span-to-length ratio of 0.6 ≤SR*≤ 0.8. The twine Reynolds number is Ret*∈[800:1600], making it experience various local drag coefficients. The DT was built with OrcaFlex (OF) aiming at: (i) avoiding over- or under-designing the system; (ii) supporting the scale-up of the system; and (iii) estimating the costs and/or the impact of our offshore operations. Therefore, we present an attempt to build an accurate DT using data from the Great Pacific Garbage Patch (GPGP). We developed a three-cycle validation: (i) initial guess applying Naumov’s semi-empirical drag coefficient to define the OF drag coefficients without the influence of the angles of attack θ of the wings; (ii) adjustment of the OF drag coefficients using AquaSim (AS) with its twine-by-twine drag correlation for various θ; (iii) re-adjustment of the OF drag coefficients from two-dimensional CFD simulations using Direct Numerical Simulation (DNS) for a twine-by-twine establishment of a drag correlation on a 1 m plane net, highlighting the shielding effects for θ<24°. Consequently, an initial underestimation of −3% in the combined towline tension, for a nominal span (SR*=0.6), was corrected to a slight overestimation of +7% compared to the GPGP data. For a wide span (SR*=0.8), the deviation remained between +1% and +15% throughout the validation process. For a narrow span (SR*∼ 0.02), mostly exhibiting low θ, the first cycle showed a +276% deviation, whereas at the end of the third cycle, it showed a +43% deviation.

Making optimal decisions in the face of noise requires balancing short-term speed and accuracy. But a theory of optimality should account for the fact that short-term speed can influence long-term accuracy through learning. Here, we demonstrate that long-term learning is an important dynamical dimension of the speed-accuracy trade-off. We study learning trajectories in rats and formally characterize these dynamics in a theory expressed as both a recurrent neural network and an analytical extension of the drift-diffusion model that learns over time. The model reveals that choosing suboptimal response times to learn faster sacrifices immediate reward, but can lead to greater total reward. We empirically verify predictions of the theory, including a relationship between stimulus exposure and learning speed, and a modulation of reaction time by future learning prospects. We find that rats’ strategies approximately maximize total reward over the full learning epoch, suggesting cognitive control over the learning process.

Preference assessments are often used to identify stimuli that function as potential reinforcers for training or intervention purposes. Specifically, various preference assessment formats have been used to identify preferred stimuli for humans, cockroaches, cotton-top tamarins, tortoises, and wolves, to name a few. However, to date, no study has evaluated the differential efficacy between food and leisure stimuli within domestic dogs. The current study aimed to compare the reinforcing value and efficacy between food and leisure stimuli for domestic dogs by comparing rates of behavior when receiving access to either their top-preferred food or leisure items. Overall results suggest (1) domestic dogs prefer food over leisure items, and (2) food is more likely to function as a reinforcer than leisure items for domestic dog’s behavior. These results suggest that dog owners and trainers should consider using food reinforcers over leisure items as reinforcers when attempting to train dogs.