A unified approach to explain contrary effects of hysteresis and smoothing in nonsmooth systems

Piecewise smooth dynamical systems make use of discontinuities to model switching between regions of smooth evolution. This introduces an ambiguity in prescribing dynamics at the discontinuity: should it be given by a limiting value on one side or other of the discontinuity, or a member of some set containing those values? One way to remove the ambiguity is to regularize the discontinuity, the most common being either to smooth out the discontinuity, or to introduce a hysteresis between switching in one direction or the other across the discontinuity. Here we show that the two can in general lead to qualitatively different dynamical outcomes. We then define a higher dimensional model with both smoothing and hysteresis, and study the competing limits in which hysteretic or smoothing effect dominate the behaviour, only the former of which correspond to Filippov's standard `sliding modes'

The effect of neuromuscular blockade on mask ventilation

Summary We wished to test the hypothesis that neuromuscular blockade facilitates mask ventilation. In order reliably and reproducibly to assess the efficiency of mask ventilation, we developed a novel grading scale (Warters scale), based on attempts to generate a standardised tidal volume. Following induction of general anaesthesia, a blinded anaesthesia provider assessed mask ventilation in 90 patients using our novel grading scale. The non-blinded anaesthesiologist then randomly administered rocuronium or normal saline. After 2 min, mask ventilation was reassessed by the blinded practitioner. Rocuronium significantly improved ventilation scores on the Warters scale (mean (SD) 2.3 (1.6) vs 1.2 (0.9), p < 0.001). In a subgroup of patients with a baseline Warters scale value of > 3 (i.e. difficult to mask ventilate; n = 14), the ventilation scores also showed significant improvement (4.2 (1.2) vs 1.9 (1.0), p = 0.0002). Saline administration had no effect on ventilation scores. Our data indicate that neuromuscular blockade facilitates mask ventilation. We discuss the implications of this finding for unexpected difficult airway management and for the practice of confirming adequate mask ventilation before the administration of neuromuscular blockade

The impact of the demographic transition on dengue in Thailand: Insights from a statistical analysis and mathematical modeling

Background: An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings: Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions: Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon

Stochastic analysis of exit fluid temperature records from the active TAG hydrothermal mound (Mid-Atlantic Ridge, 26°N) : 2. Hidden Markov models of flow episodes

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): B09102, doi:10.1029/2007JB004961.I develop a stochastic signal model for episodic modes of variability in hydrothermal flow records using probabilistic functions of Markov processes (i.e., hidden Markov models, HMMs) and fit the model to exit fluid temperature time series data from diffuse flow sites on the active TAG hydrothermal mound. The flow states are modeled using Gamma densities to provide flexibility for application to a range of signal types. Between three and five flow states are needed to fit the diffuse flow temperature records from TAG, which correspond to models with between 10 and 28 degrees of freedom. The number of flow states required to fit a given record is related to the signal variance, with more variable records requiring a larger state space. HMMs thus provide an efficient signal model for episodic variability in hydrothermal flow records, suggesting that Markov processes may provide a means to generate stochastic subsurface flow models for deep-sea hydrothermal fields if the spatial flow correlations can be incorporated into a statistical framework. I also use the Viterbi algorithm to “decode” the time series data into best fitting state sequences, which can be used to classify the records into discrete flow episodes. This may provide an objective means to identify discrete events in a flow record if misclassification issues arising from nonepisodic variability (e.g., tidal forcing) can be addressed.This work was supported by the National Science Foundation (OCE-0137329)

Multiple Cytokines Are Released When Blood from Patients with Tuberculosis Is Stimulated with Mycobacterium tuberculosis Antigens

Mycobacterium tuberculosis (Mtb) infection may cause overt disease or remain latent. Interferon gamma release assays (IGRAs) detect Mtb infection, both latent infection and infection manifesting as overt disease, by measuring whole-blood interferon gamma (IFN-γ) responses to Mtb antigens such as early secreted antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7. Due to a lack of adequate diagnostic standards for confirming latent Mtb infection, IGRA sensitivity for detecting Mtb infection has been estimated using patients with culture-confirmed tuberculosis (CCTB) for whom recovery of Mtb confirms the infection. In this study, cytokines in addition to IFN-γ were assessed for potential to provide robust measures of Mtb infection.Cytokine responses to ESAT-6, CFP-10, TB7.7, or combinations of these Mtb antigens, for patients with CCTB were compared with responses for subjects at low risk for Mtb infection (controls). Three different multiplexed immunoassays were used to measure concentrations of 9 to 20 different cytokines. Responses were calculated by subtracting background cytokine concentrations from cytokine concentrations in plasma from blood stimulated with Mtb antigens.Two assays demonstrated that ESAT-6, CFP-10, ESAT-6+CFP-10, and ESAT-6+CFP-10+TB7.7 stimulated the release of significantly greater amounts of IFN-γ, IL-2, IL-8, MCP-1 and MIP-1β for CCTB patients than for controls. Responses to combination antigens were, or tended to be, greater than responses to individual antigens. A third assay, using whole blood stimulation with ESAT-6+CFP-10+TB7.7, revealed significantly greater IFN-γ, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1β, and TNF-α responses among patients compared with controls. One CCTB patient with a falsely negative IFN-γ response had elevated responses with other cytokines.Multiple cytokines are released when whole blood from patients with CCTB is stimulated with Mtb antigens. Measurement of multiple cytokine responses may improve diagnostic sensitivity for Mtb infection compared with assessment of IFN-γ alone

Skin-Test Screening and Tuberculosis Transmission among the Homeless1

We describe the implementation of a mandatory tuberculosis (TB) screening program that uses symptom screening and tuberculin skin testing in homeless shelters. We used the results of DNA fingerprinting of Mycobacterium tuberculosis isolates to evaluate the effect of the program on TB incidence and transmission. After the program was implemented, the proportion of cases among homeless persons detected by screening activities increased, and the estimated TB incidence decreased from 510 to 121 cases per 100,000 population per year. Recent transmission, defined by DNA fingerprinting analysis as clustered patterns occurring within 2 years, decreased from 49% to 14% (p=0.03). Our results suggest that the shelter-based screening program decreased the incidence of TB by decreasing its transmission among the homeless

Stochastic analysis of exit fluid temperature records from the active TAG hydrothermal mound (Mid-Atlantic Ridge, 26°N) : 1. Modes of variability and implications for subsurface flow

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): B07101, doi:10.1029/2006JB004435.Yearlong time series records of exit fluid temperature from the active TAG hydrothermal mound (Mid-Atlantic Ridge, 26°N) reveal a complex space-time pattern of flow variability within the mineral deposit. Exit fluid temperatures were measured every 8–10 min from 17 sites distributed across the upper terrace of the mound from June 2003 to June 2004. High-temperature records were obtained using Deep Sea Power and Light SeaLogger® probes deployed in fractures discharging ∼360°C black smoker fluids, and low-temperature records were obtained using VEMCO Ltd. Minilog probes deployed in cracks discharging ∼20°C diffuse flow fluids. The temperature records are considerably more variable than those acquired from vent fields on the fast spreading East Pacific Rise and exhibit a complex mix of both episodic and periodic variability. The diffuse flow records alternate between periods of discharge and periods of what I infer to be recharge when fluid temperatures are equal to background water column levels (∼2.7°C) as ambient seawater is drawn into the seafloor. The space-time patterns of these episodic variations suggest that they represent reorganizations of the secondary circulation system driving diffuse discharge on the upper terrace of the mound on timescales from a few hours to a few days, most likely in response to permeability perturbations. Harmonic temperature oscillations were observed over a range of periods, with the principal lunar semidiurnal tidal period (M2) being most dominant. During certain times, exit fluid temperatures at diffuse sites pulse at diurnal and semidiurnal tidal periods when they are hovering near background water column levels, which I interpret as flow reversals associated with the vertical displacement of a fluid boundary layer at the seafloor interface when the local net flux is near zero. The pulsing behavior is predicted by poroelastic models of tidal loading but is not consistent with effects from tidal currents, which demonstrates that poroelastic effects from tidal loading modulate shallow subsurface flow at the active TAG mound.This work was supported by the National Science Foundation (OCE-0137329)

Day-care, early common infections and childhood acute leukaemia: a multicentre French case–control study

We conducted a case–control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4–1.0)), repeated early common infections (⩾4 per year before age two, odds ratio=0.6 (0.4–1.0)), surgical procedures for ear–nose–throat infections before age two (odds ratio=0.5 (0.2–1.0)) and prolonged breast-feeding (⩾6 months, odds ratio=0.5 (0.2–1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5–2.3) and odds ratio=0.8 (0.5–1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1–0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia