Discrete and continuous compositions

This paper examines a dataset which is modeled well by thePoisson-Log Normal process and by this process mixed with LogNormal data, which are both turned into compositions. Thisgenerates compositional data that has zeros without any need forconditional models or assuming that there is missing or censoreddata that needs adjustment. It also enables us to model dependenceon covariates and within the composition

Quantified set inversion with applications to control

This paper describes a new reliable method, based on modal interval analysis (MIA) and set inversion (SI) techniques, for the characterization of solution sets defined by quantified constraints satisfaction problems (QCSP) over continuous domains. The presented methodology, called quantified set inversion (QSI), can be used over a wide range of engineering problems involving uncertain nonlinear models. Finally, an application on parameter identification is presented

"The 3/3 strategy": a successful multifaceted hospital wide hand hygiene intervention based on WHO and continuous quality improvement methodology.

BACKGROUND Only multifaceted hospital wide interventions have been successful in achieving sustained improvements in hand hygiene (HH) compliance. METHODOLOGY/PRINCIPAL FINDINGS Pre-post intervention study of HH performance at baseline (October 2007-December 2009) and during intervention, which included two phases. Phase 1 (2010) included multimodal WHO approach. Phase 2 (2011) added Continuous Quality Improvement (CQI) tools and was based on: a) Increase of alcohol hand rub (AHR) solution placement (from 0.57 dispensers/bed to 1.56); b) Increase in frequency of audits (three days every three weeks: "3/3 strategy"); c) Implementation of a standardized register form of HH corrective actions; d) Statistical Process Control (SPC) as time series analysis methodology through appropriate control charts. During the intervention period we performed 819 scheduled direct observation audits which provided data from 11,714 HH opportunities. The most remarkable findings were: a) significant improvements in HH compliance with respect to baseline (25% mean increase); b) sustained high level (82%) of HH compliance during intervention; c) significant increase in AHRs consumption over time; c) significant decrease in the rate of healthcare-acquired MRSA; d) small but significant improvements in HH compliance when comparing phase 2 to phase 1 [79.5% (95% CI: 78.2-80.7) vs 84.6% (95% CI:83.8-85.4), p<0.05]; e) successful use of control charts to identify significant negative and positive deviations (special causes) related to the HH compliance process over time ("positive": 90.1% as highest HH compliance coinciding with the "World hygiene day"; and "negative":73.7% as lowest HH compliance coinciding with a statutory lay-off proceeding). CONCLUSIONS/SIGNIFICANCE CQI tools may be a key addition to WHO strategy to maintain a good HH performance over time. In addition, SPC has shown to be a powerful methodology to detect special causes in HH performance (positive and negative) and to help establishing adequate feedback to healthcare workers.

Single-injection or continuous femoral nerve block for total knee arthroplasty?

BACKGROUND: The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty (TKA) remains undefined. QUESTIONS/PURPOSES: We compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine (1) time to discharge readiness; (2) early pain scores and analgesic consumption; and (3) functional outcomes, including range of motion and WOMAC scores at the time of recovery. METHODS: Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this randomized, placebo-controlled, double-blind trial: a high concentration group (ropivacaine 0.2% infusion), a low concentration group (ropivacaine 0.1% infusion), or a placebo infusion group (saline 0.9% infusion). Infusions were discontinued on postoperative Day (POD) 2. The primary outcome was time to discharge readiness. Secondary outcomes included opioid consumption, pain, and functional outcomes. Ninety-three patients completed the study protocol; the study was halted early because of unanticipated changes to pain protocols at the host institution, by which time only 61% of the required number of patients had been enrolled. RESULTS: With the numbers available, the mean time to discharge readiness was not different between groups (high concentration group, 62 hours [95% confidence interval [CI], 51-72 hours]; low concentration group, 73 hours [95% CI, 63-83 hours]; placebo infusion group 65 hours [95% CI, 56-75 hours]; p = 0.27). Patients in the low concentration group consumed significantly less morphine during the period of infusion (POD 1, high concentration group, 56 mg [95% CI, 42-70 mg]; low concentration group, 35 mg [95% CI, 27-43 mg]; placebo infusion group, 48 mg [95% CI, 38-59 mg], p = 0.02; POD 2, high concentration group, 50 mg [95% CI, 41-60 mg]; low concentration group, 33 mg [95% CI, 24-42 mg]; placebo infusion group, 39 mg [95% CI, 30-48 mg], p = 0.04); however, there were no important differences in pain scores or opioid-related side effects with the numbers available. Likewise, there were no important differences in functional outcomes between groups. CONCLUSIONS: Based on this study, which was terminated prematurely before the desired sample size could be achieved, we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA. A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores, side effects, or functional outcomes. These pilot data may be used to inform the statistical power of future randomized trials. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines.

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxyprogesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non-significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti-cancer agents.

A continuous strain-space model of viral evolution within a host

Viruses rapidly evolve, and HIV in particular is known to be one of the fastest evolving human viruses. It is now commonly accepted that viral evolution is the cause of the intriguing dynamics exhibited during HIV infections and the ultimate success of the virus in its struggle with the immune system. To study viral evolution, we use a simple mathematical model of the within-host dynamics of HIV which incorporates random mutations. In this model, we assume a continuous distribution of viral strains in a one-dimensional phenotype space where random mutations are modelled by di ffusion. Numerical simulations show that random mutations combined with competition result in evolution towards higher Darwinian fitness: a stable traveling wave of evolution, moving towards higher levels of fi tness, is formed in the phenoty space.

A general continuous auction model with insiders

We analyse in a unified way how the presence of a trader with privilege information makes the market to be efficient when the release time is known. We establish a general relation between the problem of finding an equilibrium and the problem of enlargement of filtrations. We also consider the case where the time of announcement is random. In such a case the market is not fully efficient and there exists equilibrium if the sensitivity of prices with respect to the global demand is time decreasing according with the distribution of the random time.

Nasal trauma due to continuous positive airway pressure in neonates.

PATIENTS: All neonates admitted between January 2002 and December 2007 treated by nCPAP were eligible. METHODS: Patients' noses were monitored during nCPAP. Nasal trauma was reported into three stages: (I) persistent erythema; (II) superficial ulceration; and (III) necrosis. RESULTS: 989 neonates were enrolled. Mean gestational age was 34 weeks (SD 4), mean birth weight 2142 g (SD 840). Nasal trauma was reported in 420 (42.5%) patients and it was of stage I, II and III in 371 (88.3%), 46 (11%) and 3 (0.7%) patients, respectively. Incidence and severity of trauma were inversely correlated with gestational age and birth weight. The risk of nasal trauma was greater in neonates <32 weeks of gestational age (OR 2.48, 95% CI 1.59 to 3.86), weighing <1500 g at birth (OR 2.28, 95% CI 1.43 to 3.64), treated >5 days by nCPAP (OR 5.36, 95% CI 3.82 to 7.52), or staying >14 days in the NICU (OR 1.67, 95% CI 1.22 to 2.28). Most cases of nasal trauma (90%) appeared during the first 6 days of nCPAP. Persistent visible scars were present in two cases. CONCLUSIONS: Nasal trauma is a frequent complication of nCPAP, especially in preterm neonates, but long-term cosmetic sequelae are very rare. This study provides a description of nasal trauma and proposes a simple staging system. This could serve as a basis to develop strategies of prevention and treatment of this iatrogenic event.

Modeling of hybrid systems by piecewise decomposition

Piecewise linear models systems arise as mathematical models of systems in many practical applications, often from linearization for nonlinear systems. There are two main approaches of dealing with these systems according to their continuous or discrete-time aspects. We propose an approach which is based on the state transformation, more particularly the partition of the phase portrait in different regions where each subregion is modeled as a two-dimensional linear time invariant system. Then the Takagi-Sugeno model, which is a combination of local model is calculated. The simulation results show that the Alpha partition is well-suited for dealing with such a system

Cardio-pulmonary interaction in premature newborn with nasal continuous positive airways pressure (n-CPAP) respiratory assistance evaluated with echocardiography

Introduction: Nasal continuous positive airways pressure (n-CPAP) is an effective treatment in premature infants with respiratory distress. The cardio-pulmonary interactions secondary to n-CPAP are well studied in adults, but less well described in premature infants. We postulated that there could be important interactions with regard to the patent ductus arteriosus (PDA). Methods: Prospective study, approved by the local ethic committee. Premature infants less than 32 weeks gestation, _7 days-old, needing n-CPAP for respiratory distress, but without the need of additional oxygen were included in the study. Every patient had a first echocardiography with n-CPAP and then n-CPAP was retrieved. 3 hours later the echocardiography was repeated by the same investigator and then the patient replaced on n-CPAP. Results: 14 premature newborn were included, mean gestational age of 28 _ 2 weeks, mean weight 1.1 _ 0.3 Kg and height 39 _ 3 cm. Echocardiographic measurements are depicted in Table 1. Significant finding were observed between measurement on n- CPAP or without n-CPAP: on end diastolic left ventricular diameter (12.8 _ 1.6 mm vs. 13.5 _ 2 mm), on end systolic left ventricular diameter (8.4 _ 1.3 mm vs. 9.1 _ 1.5 mm), left atrium diameter (8.9 _ 2.2 mm vs. 10.4 _ 2.5 mm), maximal velocity on tricuspid valve (46 _ 10 cm/s vs. 51 _ 9 cm/s), calculated Qp (3.7 _ 0.8 L/min/m2 vs. 4.3 _ 0.8 L/min/m2). Only three patients have demonstrated a PDA during the study. Conclusion: Positive end expiratory pressure (Peep) has hemodynamic effects which are: reduction of systemic and pulmonary venous return as shown by the changes on tricuspid valve inflow,on the calculated Qp and finally on the diameter of the left atrium and left ventricle.We found in premature infants the same hemodynamic effects than those described in adults but with lower Peep values. This could be due to the particular elasticity and weakness of the thoracic wall of premature infants. Interestingly the flow through a PDA seems also to be diminished with Peep, but the number of patients is insufficient to conclude. Further investigation will be needed to better understand these interactions. Table 1. Echocardiographic measurement (mean (SD)). With n-CPAP Without n-CPAP p value RV ED diameter (mm) 6.3 (1.7) 6.04 (1.1) NS LV ED diameter (mm) 12.8 (1.6) 13.5 (2.0) _0.05 LV ES diameter (mm) 8.4 (1.3) 9.1 (1.5) _0.05 SF (%) 34 (5) 33 (6) NS Ao valve diameter (mm) 7.4 (1.3) 7.4 (1.2) NS LA diameter (mm) 8.9 (2.2) 10.4 (2.5) _0.05 Vmax Ao (cm/s) 70 (16) 71 (18) NS Vmax PV (cm/s) 69 (15) 72 (16) NS Vmax TV (cm/s) 46 (10) 51 (9) _0.05 Vmax MV (cm/s) 53 (17) 54 (18) NS Qp (L/min/m2) 3.7 (0.8) 4.3 (0.8) _0.05 Qs (L/min/m2) 4.0 (0.8) 4.0 (0.7) NS Qp/Qs 0.92 (0.14) 1.09 (0.23) _0.05 RV: right ventricle, LV: left ventricle, ED: end diastolic, ES: end systolic, SF: shortening fraction,Ao: aortic valve, LA: left atrium,Vmax: maximum Doppler Velocity, Qp: pulmonary output, Qs: systemic output, NS: non significant.

Impact of perinatal factors on continuous early monitoring of brain electrocortical activity in very preterm newborns by amplitude-integrated EEG.

Background:Amplitude-integrated electroencephalogram (aEEG) is increasingly used for neuromonitoring in preterms. We aimed to quantify the effects of gestational age (GA), postnatal age (PNA), and other perinatal factors on the development of aEEG early after birth in very preterm newborns with normal cerebral ultrasounds.Methods:Continuous aEEG was prospectively performed in 96 newborns (mean GA: 29.5 (range: 24.4-31.9) wk, birth weight 1,260 (580-2,120) g) during the first 96 h of life. aEEG tracings were qualitatively (maturity scores) and quantitatively (amplitudes) evaluated using preestablished criteria.Results:A significant increase in all aEEG measures was observed between day 1 and day 4 and for increasing GA (P < 0.001). The effect of PNA on aEEG development was 6.4- to 11.3-fold higher than that of GA. In multivariate regression, GA and PNA were associated with increased qualitative and quantitative aEEG measures, whereas small-for-GA status was independently associated with increased maximum aEEG amplitude (P = 0.003). Morphine administration negatively affected all aEEG measures (P < .05), and caffeine administration negatively affected qualitative aEEG measures (P = 0.02).Conclusion:During the first few days after birth, aEEG activity in very preterm infants significantly develops and is strongly subjected to the effect of PNA. Perinatal factors may alter the early aEEG tracing and interfere with its interpretation.

Continuous-time formulation of reaction-diffusion processes on heterogeneous metapopulations

We present the derivation of the continuous-time equations governing the limit dynamics of discrete-time reaction-diffusion processes defined on heterogeneous metapopulations. We show that, when a rigorous time limit is performed, the lack of an epidemic threshold in the spread of infections is not limited to metapopulations with a scale-free architecture, as it has been predicted from dynamical equations in which reaction and diffusion occur sequentially in time

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.

Fault diagnosis by refining the parameter uncertainty space of nonlinear dynamic systems

This paper deals with fault detection and isolation problems for nonlinear dynamic systems. Both problems are stated as constraint satisfaction problems (CSP) and solved using consistency techniques. The main contribution is the isolation method based on consistency techniques and uncertainty space refining of interval parameters. The major advantage of this method is that the isolation speed is fast even taking into account uncertainty in parameters, measurements, and model errors. Interval calculations bring independence from the assumption of monotony considered by several approaches for fault isolation which are based on observers. An application to a well known alcoholic fermentation process model is presented

Robust fault detection using consistency techniques for uncertainty handling

Often practical performance of analytical redundancy for fault detection and diagnosis is decreased by uncertainties prevailing not only in the system model, but also in the measurements. In this paper, the problem of fault detection is stated as a constraint satisfaction problem over continuous domains with a big number of variables and constraints. This problem can be solved using modal interval analysis and consistency techniques. Consistency techniques are then shown to be particularly efficient to check the consistency of the analytical redundancy relations (ARRs), dealing with uncertain measurements and parameters. Through the work presented in this paper, it can be observed that consistency techniques can be used to increase the performance of a robust fault detection tool, which is based on interval arithmetic. The proposed method is illustrated using a nonlinear dynamic model of a hydraulic system