O-Minimal Hybrid Reachability Games

In this paper, we consider reachability games over general hybrid systems, and distinguish between two possible observation frameworks for those games: either the precise dynamics of the system is seen by the players (this is the perfect observation framework), or only the starting point and the delays are known by the players (this is the partial observation framework). In the first more classical framework, we show that time-abstract bisimulation is not adequate for solving this problem, although it is sufficient in the case of timed automata . That is why we consider an other equivalence, namely the suffix equivalence based on the encoding of trajectories through words. We show that this suffix equivalence is in general a correct abstraction for games. We apply this result to o-minimal hybrid systems, and get decidability and computability results in this framework. For the second framework which assumes a partial observation of the dynamics of the system, we propose another abstraction, called the superword encoding, which is suitable to solve the games under that assumption. In that framework, we also provide decidability and computability results

Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non–small cell lung cancer

AbstractObjective: The purpose of this study was to evaluate postchemoradiotherapy surgery in stage IIIB non–small cell lung cancer. Methods: Forty patients with stage IIIB non–small cell lung cancer were included in this phase II study. A preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a thoracotomy in all patients. Induction treatment included two cycles of cisplatin (100 mg/m2, day 1), 5-fluorouracil (1 g/m2, days 1-3), and vinblastine (4 mg/m2, day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering 21 Gy in two sessions. Patients with a clinical response were offered surgery. Results: The minimum follow-up for survivors was 48 months. Thirty patients had a T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical objective tumor response after induction treatment. These 29 patients underwent thoracotomy, and a complete resection was performed in 23 (58%). Two postoperative deaths occurred (7%). Four patients had a pathologic complete response at the time of surgery (10%). The 5-year survival is 19% for the overall population. When only patients who had persistent viable tumor cells at surgery are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42% for patients having no mediastinal lymph node involvement at the time of surgery and being treated with complete resection. Conclusion: This study shows that surgery, when feasible, is associated with a 28% long-term survival for patients in whom chemoradiotherapy alone fails to control disease

Predictors of mortality and short-term physical and cognitive dependence in critically ill persons 75 years and older: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors.</p> <p>Methods</p> <p>We conducted a prospective observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period, except those admitted after cardiac arrest, All patients were followed for 3 months or until death. Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living (ADL). Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile (NHP) score.</p> <p>Results</p> <p>One hundred patients were included in the analysis. The mean age was 79.3 ± 3.4 years. The median Charlson index was 6 [IQR, 4 to 7] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4, respectively, corresponding to a population with a high level of comorbidities but low physical and cognitive dependence. Mortality was 61/100 (61%) at 3 months. In multivariate analysis only comorbidities assessed by the Charlson index [Adjusted Odds Ratio, 1.6; 95% CI, 1.2-2.2; <it>p </it>< 0.003] and the number of organ failures assessed by the SOFA score [Adjusted Odds Ratio, 2.5; 95% CI, 1.1-5.2; <it>p </it>< 0.02] were independently associated with 3-month mortality. All 22 patients needing renal support after Day 3 died. Compared with pre-admission, physical (<it>p </it>= 0.04), and cognitive (<it>p </it>= 0.62) dependence in survivors had changed very little at 3 months. In addition, the mean NHP score was 213.1 <b>± </b>132.8 at 3 months, suggesting an acceptable perception of their quality of life.</p> <p>Conclusions</p> <p>In a selected population of non surgical patients 75 years and older, admission into the ICU is associated with a 3-month survival rate of 38% with little impact on physical and cognitive dependence and subjective health status. Nevertheless, a high comorbidity level (ie, Charlson index), multi-organ failure, and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death.</p

P2X7 Receptor Promotes Mouse Mammary Cancer Cell Invasiveness and Tumour Progression, and Is a Target for Anticancer Treatment

The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment

Involvement of the Efflux Pumps in Chloramphenicol Selected Strains of Burkholderia thailandensis: Proteomic and Mechanistic Evidence

Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections

Infection of Wildlife by Mycobacterium bovis in France Assessment Through a National Surveillance System, Sylvatub

Mycobacterium bovis infection was first described in free-ranging wildlife in France in 2001, with subsequent detection in hunter-harvested ungulates and badgers in areas where outbreaks of bovine tuberculosis (TB) were also detected in cattle. Increasing concerns regarding TB in wildlife led the French General Directorate for Food (DGAL) and the main institutions involved in animal health and wildlife management, to establish a national surveillance system for TB in free-ranging wildlife. This surveillance system is known as “Sylvatub.” The system coordinates the activities of various national and local partners. The main goal of Sylvatub is to detect and monitor M. bovis infection in wildlife through a combination of passive and active surveillance protocols adapted to the estimated risk level in each area of the country. Event-base surveillance relies on M. bovis identification (molecular detection) (i) in gross lesions detected in hunter-harvested ungulates, (ii) in ungulates that are found dead or dying, and (iii) in road-killed badgers. Additional targeted surveillance in badgers, wild boars and red deer is implemented on samples from trapped or hunted animals in at-risk areas. With the exception of one unexplained case in a wild boar, M. bovis infection in free-living wildlife has always been detected in the vicinity of cattle TB outbreaks with the same genotype of the infectious M. bovis strains. Since 2012, M. bovis was actively monitored in these infected areas and detected mainly in badgers and wild boars with apparent infection rates of 4.57–5.14% and 2.37–3.04%, respectively depending of the diagnostic test used (culture or PCR), the period and according to areas. Sporadic infection has also been detected in red deer and roe deer. This surveillance has demonstrated that M. bovis infection, in different areas of France, involves a multi-host system including cattle and wildlife. However, infection rates are lower than those observed in badgers in the United Kingdom or in wild boars in Spain

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements