Linear stochastic differential algebraic equations with constant coefficients

We consider linear stochastic differential-algebraic equations with constant coefficients and additive white noise. Due to the nature of this class of equations, the solution must be defined as a generalised process (in the sense of Dawson and Fernique). We provide sufficient conditions for the law of the variables of the solution process to be absolutely continuous with respect to Lebesgue measure.

Renal sodium handling and nighttime blood pressure.

Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure.

Ambulatory blood pressure monitoring in adolescent untreated hypertensive patients.

Ambulatory blood pressure profiles were obtained with the portable semi-automatic blood pressure recorder Remler M2000 in groups of 20 adolescents, 20 young and 20 middle-aged adults and 20 elderly untreated patients, all considered by their physician to be hypertensive. It was found that adolescents who are hypertensive when seeing their physician are more often normotensive outside the physician's office than adult and elderly patients under similar conditions. The increased heart rate variability which was detected in adolescents was not associated with an enhanced blood pressure variability.

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Atrial natriuretic peptides: reproducibility of renal effects and response of liver blood flow.

To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 microgram/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow. Blood pressure, heart rate and the plasma levels of angiotensin II, aldosterone, arginine vasopressin and plasma renin activity were unaltered. The effect of a 2-h infusion of ANP 0.5 microgram/min or its vehicle on apparent hepatic blood flow (HBF) was also studied in 14 normal volunteers by measuring the indocyanine green clearance. A 21% decrease in HBF was observed in subjects who received the ANP infusion (p less than 0.01 vs vehicle). Thus, ANP infused at a dose that did not lower blood pressure decreased both renal and liver blood flow in normotensive volunteers. The renal and endocrine responses to ANP were reproducible over a 1-week interval.

Quantification of clenbuterol at trace level in human urine by ultra-high pressure liquid chromatography-tandem mass spectrometry.

Clenbuterol is a β2 agonist agent with anabolic properties given by the increase in the muscular mass in parallel to the decrease of the body fat. For this reason, the use of clenbuterol is forbidden by the World Anti-Doping Agency (WADA) in the practice of sport. This compound is of particular interest for anti-doping authorities and WADA-accredited laboratories due to the recent reporting of risk of unintentional doping following the eating of meat contaminated with traces of clenbuterol in some countries. In this work, the development and the validation of an ultra-high pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the quantification of clenbuterol in human urine is described. The analyte was extracted from urine samples by liquid-liquid extraction (LLE) in basic conditions using tert butyl-methyl ether (TBME) and analyzed by UHPLC-MS/MS with a linear gradient of acetonitrile in 9min only. The simple and rapid method presented here was validated in compliance with authority guidelines and showed a limit of quantification at 5pg/mL and a linearity range from 5pg/mL to 300pg/mL. Good trueness (85.8-105%), repeatability (5.7-10.6% RSD) and intermediate precision (5.9-14.9% RSD) results were obtained. The method was then applied to real samples from eighteen volunteers collecting urines after single oral doses administration (1, 5 and 10μg) of clenbuterol-enriched yogurts.

In vivo characterization of the circadian clock output gene usp2

Life on earth is subject to the repeated change between day and night periods. All organisms that undergo these alterations have to anticipate consequently the adaptation of their physiology and possess an endogenous periodicity of about 24 hours called circadian rhythm from the Latin circa (about) and diem (day). At the molecular level, virtually all cells of an organism possess a molecular clock which drives rhythmic gene expression and output functions. Besides altered rhythmicity in constant conditions, impaired clock function causes pathophysiological conditions such as diabetes or hypertension. These data unveil a part of the mechanisms underlying the well-described epidemiology of shift work and highlight the function of clock-driven regulatory mechanisms. The post-translational modification of proteins by the ubiquitin polypeptide is a central mechanism to regulate their stability and activity and is capital for clock function. Similarly to the majority of biological processes, it is reversible. Deubiquitylation is carried out by a wide variety of about ninety deubiquitylating enzymes and their function remains poorly understood, especially in vivo. This class of proteolytic enzymes is parted into five families including the Ubiquitin-Specific Proteases (USP), which is the most important with about sixty members. Among them, the Ubiquitin-Specific Protease 2 (Usp2) gene encodes two protein isoforms, USP2-45 and USP2-69. The first is ubiquitously expressed under the control of the circadian clock and displays all features of core clock genes or its closest outputs effectors. Additionally, Usp2-45 was also found to be induced by the mineralocorticoid hormone aldosterone and thought to participate in Na+ reabsorption and blood pressure regulation by Epithelial Na+ Channel ENaC in the kidneys. During my thesis, I aimed to characterize the role of Usp2 in vivo with respect to these two areas, by taking advantage of a total constitutive knockout mouse model. In the first project I aimed to validate the role of USP2-45 in Na+ homeostasis and blood pressure regulation by the kidneys. I found no significant alterations of diurnal Na+ homeostasis and blood pressure in these mice, indicating that Usp2 does not play a substantial role in this process. In urine analyses, we found that our Usp2-KO mice are actually hypercalciuric. In a second project, I aimed to understand the causes of this phenotype. I found that the observed hypercalciuria results essentially from intestinal hyperabsorption. These data reveal a new role for Usp2 as an output effector of the circadian clock in dietary Ca2+ metabolism in the intestine.

Adiposity indicators and blood pressure in children: nothing beyond body mass index?

Obesity is a major risk factor for elevated blood pressure in children. For instance, in a school-based study of 5207 children aged 10-12 years, the prevalence of hypertension, which is sustained elevated blood pressure over several visits, was 1.5%, 3.9% and 17.5% in normal weight, overweight and obese children, respectively. High body mass index (BMI) is commonly used to define overweight and obesity. However, because BMI is merely a proxy for adiposity, there is a longstanding debate about its performance to predict elevated blood pressure (or any other health conditions associated with adiposity) and whether other adiposity indicators, such as waist circumference, waist-to-hip ratio or hip circumference, should not be preferred... In this study, 7.4% of boys and 6.4% of girls had elevated blood pressure. The adiposity indicators were highly correlated to each other, apart from weight, waist-to-hip ratio and skinfold thickness z-scores. All indicators were associated with blood pressure. The ability to identify children with elevated blood pressure, assessed by the area under the receiver operating curve (AUC) statistic, was superior for BMI, body adiposity index and waist-to-height ratio z-scores compared with other indicators. BMI z-scores had a slightly higher AUC than other indicators. The authors concluded that BMIz-scores could be a better predictor of elevated blood pressure in children than other adiposity indicators.

Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management.

Improving the accuracy of heat balance integral methods applied to thermal problems with time dependent boundary conditions

In this paper the two main drawbacks of the heat balance integral methods are examined. Firstly we investigate the choice of approximating function. For a standard polynomial form it is shown that combining the Heat Balance and Refined Integral methods to determine the power of the highest order term will either lead to the same, or more often, greatly improved accuracy on standard methods. Secondly we examine thermal problems with a time-dependent boundary condition. In doing so we develop a logarithmic approximating function. This new function allows us to model moving peaks in the temperature profile, a feature that previous heat balance methods cannot capture. If the boundary temperature varies so that at some time t & 0 it equals the far-field temperature, then standard methods predict that the temperature is everywhere at this constant value. The new method predicts the correct behaviour. It is also shown that this function provides even more accurate results, when coupled with the new CIM, than the polynomial profile. Analysis primarily focuses on a specified constant boundary temperature and is then extended to constant flux, Newton cooling and time dependent boundary conditions.

Life Cycle and Reproductive Patterns of Triatoma rubrofasciata (De Geer, 1773) (Hemiptera: Reduviidae), under Laboratory Conditions

The life cycle and reproductive patterns of Triatoma rubrofasciata were studied along with laboratory conditions for the establishment of a prolific colony. The insects were divided into four groups: two of them were maintained at room temperature (20.5°C to 33°C and 85% ± 5% of relative humidity), the other two in a climatic chamber (CC) (temperature: 29°C, humidity: 80% ± 5%). The groups were fed weekly or fortnightly on Swiss mice. The females from the group kept in the CC and fed weekly had longer life span, as well as a higher number of eggs, fertile eggs and hatchings; the group kept in the CC and fed fortnightly had a shorter life span for the 1st, 2nd and 3rd instars and a lower mortality rate for all instars. It was concluded that a constant high temperature (CC at 29°C) is the most suitable condition for the maintenance of a colony of T. rubrofasciata regardless of the interval between repasts.

Survival, development and growth of larvae of the blue swimmer crab, Portunus pelagicus, cultured under different photoperiod conditions

The blue swimmer crab is a commercially important species of the tropical Indo-Pacific regions that shows substantial potential as a candidate species for aquaculture. Optimization of larval rearing conditions, including photoperiod, is therefore important to establish a method for the intensive hatchery culture of this species. Newly hatched larvae of Portunuspelagicus in first zoeal stage (ZI) were reared under five photoperiod regimes 0L: 24D, 6L: 18D, 12L: 12D, 18L: 6D, and 24L: 0D (5 replicates per treatment) till they metamorphosed to megalopae (ranged from 8.5 ± 0.3 days (18L: 6D) to 10.8 ± 1.8 days (0L: 24D) at 29 ± 1 °C). Daily, larvae of each treatment were fed an identical diet of mixed rotifer and Artemia nauplii, and the survival and molt to successive stages was monitored. Newly hatched ZI larvae of P. pelagicus could successfully develop to the megalopal stage under all tested photoperiod conditions, but we detected significant differences in survival among treatments (p & 0.05). The constant darkness treatment (0L: 24D) had the lowest (19.2 ± 7.2%, mean ± S.E.) cumulative survival from ZI to the megalopal stage, while the 18L: 6D treatment achieved the highest survival (51.2 ± 23.6%). Similarly, the photoperiod significantly affected zoeal development. Constant darkness led to the longest cumulative zoeal duration (10.8 ± 1.8 days), whereas the 18L: 6D treatment rendered the shortest larval development (8.5 ± 0.3 days). In addition, larvae reared under constant darkness resulted in the smallest megalopae (carapace length = 1.44 ± 0.09 mm) and the lowest dry weight (0.536 ± 0.188 mg). In conclusion, photoperiod significantly affected the survival, development, and growth of P. pelagicus zoeal larvae. Constant darkness led to the lowest larval survival and developmental rate, while a photoperiod regime of 18L: 6D appeared to be the most suitable condition for the rearing of zoeal larvae of P. pelagicus.

Prevalence of chronic conditions – Stroke

IPH has estimated and forecast clinical diagnosis rates of stroke among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007. The data describe the number of adults who report that they have experienced doctor-diagnosed stroke in the previous 12 months. Data are available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06. The data describe the number of adults who report that they have experienced doctor-diagnosed stroke at any time in the past. Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past. The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Making Chronic Conditions Count: 4. Stroke

Chronic conditions are responsible for a significant proportion of early deaths. They reduce quality of life in many of the adults living with them, represent substantial financial costs to patients and the health and social care system, and cause a significant loss of productivity to the economy. This report contains estimates and forecasts of the population prevalence of stroke, and it shows how it varies across the island and what change is expected between 2007, 2015 and 2020.