Escape Orbits for Non-Compact Flat Billiards

It is proven that, under some conditions on $f$, the non-compact flat billiard $\Omega = \{ (x,y) \in \R_0^{+} \times \R_0^{+};\ 0\le y \le f(x) \}$ has no orbits going {\em directly} to $+\infty$. The relevance of such sufficient conditions is discussed.Comment: 9 pages, LaTeX, 3 postscript figures available at http://www.princeton.edu/~marco/papers/ . Minor changes since previously posted version. Submitted to 'Chaos

The role of observation uncertainty in the calibration of hydrologic rainfall-runoff models

International audienceHydrologic rainfall-runoff models are usually calibrated with reference to a limited number of recorded flood events, for which rainfall and runoff measurements are available. In this framework, model's parameters consistency depends on the number of both events and hydrograph points used for calibration, and on measurements reliability. Recently, to make users aware of application limits, major attention has been devoted to the estimation of uncertainty in hydrologic modelling. Here a simple numerical experiment is proposed, that allows the analysis of uncertainty in hydrologic rainfall-runoff modelling associated to both quantity and quality of available data. A distributed rainfall-runoff model based on geomorphologic concepts has been used. The experiment involves the analysis of an ensemble of model runs, and its overall set up holds if the model is to be applied in different catchments and climates, or even if a different hydrologic model is used. With reference to a set of 100 synthetic rainfall events characterized by a given rainfall volume, the effect of uncertainty in parameters calibration is studied. An artificial truth ? perfect observation ? is created by using the model in a known configuration. An external source of uncertainty is introduced by assuming realistic, i.e. uncertain, discharge observations to calibrate the model. The range of parameters' values able to "reproduce" the observation is studied. Finally, the model uncertainty is evaluated and discussed. The experiment gives useful indications about the number of both events and data points needed for a careful and stable calibration of a specific model, applied in a given climate and catchment. Moreover, an insight on the expected and maximum error in flood peak discharge simulations is given: errors ranging up to 40% are to be expected if parameters are calibrated on insufficient data sets

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised

Quantum Chaos in the Bose-Hubbard model

We present a numerical study of the spectral properties of the 1D Bose-Hubbard model. Unlike the 1D Hubbard model for fermions, this system is found to be non-integrable, and exhibits Wigner-Dyson spectral statistics under suitable conditions.Comment: 4 pages, 4 figure

Factors associated with postmenstrual age at full oral feeding in very preterm infants.

We aimed to identify variables associated with gestational age at full oral feeding in a cohort of very preterm infants. In this retrospective study, all infants born below 32 weeks of gestation and admitted to a level III neonatal unit in 2015 were included. We dichotomized our population of 122 infants through the median age at full oral feeding, and explored which variables were statistically different between the two groups. We then used linear regression analysis to study the association between variables known from the literature and variables we had identified and age at full oral feeding. The median postnatal age at full oral feeding was 36 6/7weeks post menstrual age (Q1-Q3 35 6/7-392/7), and was associated with the duration of hospital of stay. In the univariable linear regression, the variables significantly associated with full oral feeding were gestational age, socioeconomic status, sepsis, patent ductus arteriosus, duration of supplementary oxygen, of non-invasive and invasive ventilation, and bronchopulmonary dysplasia. In the multivariable regression analysis, duration of non-invasive ventilation and oxygen therapy, bronchopulmonary dysplasia, and patent ductus arteriosus were associated with an older age at full oral feeding, with bronchopulmonary dysplasia the single most potent predictor. Lung disease severity is a major determinant of age at full oral feeding and thus length of stay in this population. Other factors associated with FOF include socioeconomic status and patent ductus arteriosus, There is a need for research addressing evidence-based bundles of care for these infants at risk of long-lasting feeding and neurodevelopmental impairments

Activity of drugs against dormant Mycobacterium tuberculosis

AbstractObjective/backgroundHeterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb. Dormant Mtb remodels lipids of its cell wall, and so lipophilic drugs may be active against NR Mtb living in caseous, lipid-rich, granulomas. Lipophilicity is expressed as logP, that is, the logarithm of the partition coefficient (P) ratio Poctanol/Pwater. In this study, the activity of lipophilic drugs (logP>0) and hydrophilic drugs (logP⩽0) against AR and NR Mtb was measured in hypoxic conditions under acidic and slightly alkaline pHs.MethodsThe activity of drugs was determined against AR Mtb (5-day-old aerobic cells: A5) and NR Mtb (12- and 19-day-old hypoxic cells: H12 and H19) in a Wayne dormancy model of Mtb H37Rv at pH 5.8, to mimic the environment of cellular granulomas. Furthermore, AR and NR bacilli were grown for 40days in Wayne models at pH 6.6, 7.0, 7.4, and 7.6, to set up conditions mimicking the caseous granulomas (hypoxia+slightly alkaline pH), to measure drug activity against NR cells. Mtb viability was determined by colony-forming unit (CFU) counts.ResultsAt pH 5.8, lipophilic drugs (rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide: logP⩾2.14) reduced CFU of all cells (H12, H19, and A5) by ⩾2log10. Among hydrophilic drugs (isoniazid, pyrazinamide, ethambutol, amikacin, moxifloxacin, metronidazole: logP⩽0.01), none reduced H12 and H19 CFUs by ⩾2log10, with the exception of metronidazole. When Mtb was grown at different pHs the following Mtb growth was noted: at pH 6.6, AR cells grew fluently while NR cells grew less, with a CFU increase up to Day 15, followed by a drop to Day 40. AR and NR Mtb grown at pH 7.0, 7.4, and 7.6 showed up to 1 log10 CFU lower than their growth at pH 6.6. The pHs of all AR cultures tended to reach pH 7.2–7.4 on Day 40. The pHs of all NR cultures remained stable at their initial values (6.6, 7.0, 7.4, and 7.6) up to Day 40. The activity of drugs against H12 and H19 cells was tested in hypoxic conditions at a slightly alkaline pH. Under these conditions, some lipophilic drugs were more active (>5 log CFU decrease after 21days of exposure) against H12 and H19 cells than clofazimine, nitazoxanide, isoniazid, pyrazinamide, amikacin (<1 log CFU decrease after 21days of exposure). Testing of other drugs is in progress.ConclusionLipophilic drugs were more active than hydrophilic agents against dormant Mtb in hypoxic conditions at pH 5.8. The Wayne model under slightly alkaline conditions was set up, and in hypoxic conditions at a slightly alkaline pH some lipophilic drugs were more active than other drugs against NR Mtb. Overall, these models can be useful for testing drug activity against dormant Mtb under conditions mimicking the environments of cellular and caseous granulomas

Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models

Three-dimensional (3D) culture models have gained relevant interest in tissue engineering and drug discovery owing to their suitability to reproduce in vitro some key aspects of human tissues and to provide predictive information for in vivo tests. In this context, the use of hydrogels as artificial extracellular matrices is of paramount relevance, since they allow closer recapitulation of (patho)physiological features of human tissues. However, most of the analyses aimed at characterizing these models are based on time-consuming and endpoint assays, which can provide only static and limited data on cellular behavior. On the other hand, biosensing systems could be adopted to measure on-line cellular activity, as currently performed in bi-dimensional, i.e., monolayer, cell culture systems; however, their translation and integration within 3D hydrogel-based systems is not straight forward, due to the geometry and materials properties of these advanced cell culturing approaches. Therefore, researchers have adopted different strategies, through the development of biochemical, electrochemical and optical sensors, but challenges still remain in employing these devices. In this review, after examining recent advances in adapting existing biosensors from traditional cell monolayers to polymeric 3D cells cultures, we will focus on novel designs and outcomes of a range of biosensors specifically developed to provide real-time analysis of hydrogel-based cultures