To Adapt or Not to Adapt – Consequences of Adapting Driver and Traffic Light Agents

One way to cope with the increasing traffic demand is to integrate standard solutions with more intelligent control measures. However, the result of possible interferences between intelligent control or information provision tools and other components of the overall traffic system is not easily predictable. This paper discusses the effects of integrating co-adaptive decision-making regarding route choices (by drivers) and control measures (by traffic lights). The motivation behind this is that optimization of traffic light control is starting to be integrated with navigation support for drivers. We use microscopic, agent-based modelling and simulation, in opposition to the classical network analysis, as this work focuses on the effect of local adaptation. In a scenario that exhibits features comparable to real-world networks, we evaluate different types of adaptation by drivers and by traffic lights, based on local perceptions. In order to compare the performance, we have also used a global level optimization method based on genetic algorithms

Autonomous Intersection Driving with Neuro-Evolution

Neuro-Evolution (NE) has been used to evolve controllers in land-based vehicles that accomplish various tasks. However, there has been little work on evolving coordinated movement for maximizing traffic flow through intersections. This study used NE to synthesize collective driving behaviors for given road networks (interconnected intersections), where there were no traffic signals to assist with vehicle coordination and navigation. Rather, NE automates controller design where collective driving behavior emerges in response to the task of maximizing traffic throughput and minimizing delays at intersections

CEM03 and LAQGSM03 - new modeling tools for nuclear applications

An improved version of the Cascade-Exciton Model (CEM) of nuclear reactions realized in the code CEM2k and the Los Alamos version of the Quark-Gluon String Model (LAQGSM) have been developed recently at LANL to describe reactions induced by particles and nuclei for a number of applications. Our CEM2k and LAQGSM merged with the GEM2 evaporation/fission code by Furihata have predictive powers comparable to other modern codes and describe many reactions better than other codes; therefore both our codes can be used as reliable event generators in transport codes for applications. During the last year, we have made a significant improvements to the intranuclear cascade parts of CEM2k and LAQGSM, and have extended LAQGSM to describe photonuclear reactions at energies to 10 GeV and higher. We have produced in this way improved versions of our codes, CEM03.01 and LAQGSM03.01. We present a brief description of our codes and show illustrative results obtained with CEM03.01 and LAQGSM03.01 for different reactions compared with predictions by other models, as well as examples of using our codes as modeling tools for nuclear applications.Comment: 12 pages, 10 figures, to be published in Journal of Physics: Conference Series: Proc. Europhysics Conf. on New Trends in Nuclear Physics Applications and Technologies (NPDC19), Pavia, Italy, September 5-9, 200

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study

Background Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. Methods For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. Results A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. Conclusion This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com)

Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans

International audienceOBJECTIVE: Insulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance. RESEARCH DESIGN AND METHODS: We first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling. RESULTS: Muscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = -0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (-30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance. CONCLUSIONS: Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes

Definitive chemoradiation in patients with inoperable oesophageal carcinoma

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m-2 day-1 is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m-2 day-1, reduced to 225 mg m-2 day-1 during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery