One-dimensional model for propagation of a pressure wave in a model of the human arterial network: comparison of theoretical and experimental results

Pulse wave evaluation is an effective method for arteriosclerosis screening. In a previous study, we verified that pulse waveforms change markedly due to arterial stiffness. However, a pulse wave consists of two components, the incident wave and multireflected waves. Clarification of the complicated propagation of these waves is necessary to gain an understanding of the nature of pulse waves in vivo. In this study, we built a one-dimensional theoretical model of a pressure wave propagating in a flexible tube. To evaluate the applicability of the model, we compared theoretical estimations with measured data obtained from basic tube models and a simple arterial model. We constructed different viscoelastic tube set-ups: two straight tubes; one tube connected to two tubes of different elasticity; a single bifurcation tube; and a simple arterial network with four bifurcations. Soft polyurethane tubes were used and the configuration was based on a realistic human arterial network. The tensile modulus of the material was similar to the elasticity of arteries. A pulsatile flow with ejection time 0.3 s was applied using a controlled pump. Inner pressure waves and flow velocity were then measured using a pressure sensor and an ultrasonic diagnostic system. We formulated a 1D model derived from the Navier-Stokes equations and a continuity equation to characterize pressure propagation in flexible tubes. The theoretical model includes nonlinearity and attenuation terms due to the tube wall, and flow viscosity derived from a steady Hagen-Poiseuille profile. Under the same configuration as for experiments, the governing equations were computed using the MacCormack scheme. The theoretical pressure waves for each case showed a good fit to the experimental waves. The square sum of residuals (difference between theoretical and experimental wave-forms) for each case was <10.0%. A possible explanation for the increase in the square sum of residuals is the approximation error for flow viscosity. However, the comparatively small values prove the validity of the approach and indicate the usefulness of the model for understanding pressure propagation in the human arterial network.     

Embryonic stem cells in non-human primates: An overview of neural differentiation potential

Non-human primate (NHP) embryonic stem (ES) cells show unlimited proliferative capacities and a great potential to generate multiple cell lineages. These properties make them an ideal resource both for investigating early developmental processes and for assessing their therapeutic potential in numerous models of degenerative diseases. They share the same markers and the same properties with human ES cells, and thus provide an invaluable transitional model that can be used to address the safety issues related to the clinical use of human ES cells. Here, we review the available information on the derivation and the specific features of monkey ES cells. We comment on the capacity of primate ES cells to differentiate into neural lineages and the current protocols to generate self-renewing neural stem cells. We also highlight the signalling pathways involved in the maintenance of these neural cell types. Finally, we discuss the potential of monkey ES cells for neuronal differentiation.     

Modelling the effects of population structure on childhood disease: the case of varicella

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0-11 years old.Moreover, the individual-based model structure allowed us to reproduce several observed features of VZV epidemiology which were not included as hypotheses in the model: the age at varicella in first-born children was older than in other children, in accordance with observation; the same was true for children residing in rural areas. Model predicted incidence was comparable to observed incidence over time. These results show that models based on detailed census data on a small scale provide valid small scale prediction. By simulating several scenarios, we evaluate how varicella epidemiology is shaped by policies, such as age at first school enrolment, and school eviction. This supports the use of such models for investigating outcomes of public health measures.     

The Chikungunya epidemic on La Réunion Island in 2005-2006: a cost-of-illness study

Background

This study was conducted to assess the impact of chikungunya on health costs during the epidemic that occurred on La Réunion in 2005–2006.

Methodology/Principal Findings

From data collected from health agencies, the additional costs incurred by chikungunya in terms of consultations, drug consumption and absence from work were determined by a comparison with the expected costs outside the epidemic period. The cost of hospitalization was estimated from data provided by the national hospitalization database for short-term care by considering all hospital stays in which the ICD-10 code A92.0 appeared. A cost-of-illness study was conducted from the perspective of the third-party payer. Direct medical costs per outpatient and inpatient case were evaluated. The costs were estimated in Euros at 2006 values. Additional reimbursements for consultations with general practitioners and drugs were estimated as €12.4 million (range: €7.7 million–€17.1 million) and €5 million (€1.9 million–€8.1 million), respectively, while the cost of hospitalization for chikungunya was estimated to be €8.5 million (€5.8 million–€8.7 million). Productivity costs were estimated as €17.4 million (€6 million–€28.9 million). The medical cost of the chikungunya epidemic was estimated as €43.9 million, 60% due to direct medical costs and 40% to indirect costs (€26.5 million and €17.4 million, respectively). The direct medical cost was assessed as €90 for each outpatient and €2,000 for each inpatient.

Conclusions/Significance

The medical management of chikungunya during the epidemic on La Réunion Island was associated with an important economic burden. The estimated cost of the reported disease can be used to evaluate the cost/efficacy and cost/benefit ratios for prevention and control programmes of emerging arboviruses.     

Special care and school difficulties in 8-year-old very preterm children: the Epipage cohort study

Objectives

To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children.

Patient and Methods

Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39–40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents.

Results

Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five.

Conclusions

Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores.     

Using Digital RNA Counting and Flow Cytometry to Compare mRNA with Protein Expression in Acute Leukemias

Background

The diagnosis of malignant hematologic diseases has become increasingly complex during the last decade. It is based on the interpretation of results from different laboratory analyses, which range from microscopy to gene expression profiling. Recently, a method for the analysis of RNA phenotypes has been developed, the nCounter technology (Nanostring® Technologies), which allows for simultaneous quantification of hundreds of RNA molecules in biological samples. We evaluated this technique in a Swiss multi-center study on eighty-six samples from acute leukemia patients.

Methods

mRNA and protein profiles were established for normal peripheral blood and bone marrow samples. Signal intensities of the various tested antigens with surface expression were similar to those found in previously performed Affymetrix microarray analyses. Acute leukemia samples were analyzed for a set of twenty-two validated antigens and the Pearson Correlation Coefficient for nCounter and flow cytometry results was calculated.

Results

Highly significant values between 0.40 and 0.97 were found for the twenty-two antigens tested. A second correlation analysis performed on a per sample basis resulted in concordant results between flow cytometry and nCounter in 44–100% of the antigens tested (mean = 76%), depending on the number of blasts present in a sample, the homogeneity of the blast population, and the type of leukemia (AML or ALL).

Conclusions

The nCounter technology allows for fast and easy depiction of a mRNA profile from hematologic samples. This technology has the potential to become a valuable tool for the diagnosis of acute leukemias, in addition to multi-color flow cytometry.     

Human butyrylcholinesterase produced in insect cells: huprine-based affinity purification and crystal structure

Butyrylcholinesterase (BChE) is a serine hydrolase that is present in all mammalian tissues. It can accommodate larger substrates or inhibitors than acetylcholinesterase (AChE), the enzyme responsible for hydrolysis of the neurotransmitter acetylcholine in the central nervous system and neuromuscular junctions. AChE is the specific target of organophosphorous pesticides and warfare nerve agents, and BChE is a stoichiometric bioscavenger. Conversion of BChE into a catalytic bioscavenger by rational design or designing reactivators specific to BChE required structural data obtained using a recombinant low-glycosylated human BChE expressed in Chinese hamster ovary cells. This expression system yields ≈ 1 mg of pure enzyme per litre of cell culture. Here, we report an improved expression system using insect cells with a fourfold higher yield for truncated human BChE with all glycosylation sites present. We developed a fast purification protocol for the recombinant protein using huprine-based affinity chromatography, which is superior to the classical procainamide-based affinity. The purified BChE crystallized under different conditions and space group than the recombinant low-glycosylated protein produced in Chinese hamster ovary cells. The crystals diffracted to 2.5 ?. The overall monomer structure is similar to the low-glycosylated structure except for the presence of the additional glycans. Remarkably, the carboxylic acid molecule systematically bound to the catalytic serine in the low-glycosylated structure is also present in this new structure, despite the different expression system, purification protocol and crystallization conditions.     

Evaluation of the technical and environmental performances of extraction and purification processes of arabinoxylans from wheat straw and bran

A process for hemicelluloses fractionation and purification from wheat straw and bran has been investigated and technical considerations (yields, purity) have been coupled to environmental characterizations (water consumption, carbon dioxide emissions) in order to develop an environment-friendly process. Extraction by twin-screw extrusion gave a yield in arabinoxylans equal to 8.5% (weight of (arabinose + xylose) in the extract after fractionation/dry weight of the destarched bran). The extraction of 86 kg of straw and bran (with a ratio 6.2:1) with 5.8 kg of NaOH in pellet form resulted in the production of a complex extract containing 1.0 kg of arabinoxylan polymer, which required concentration and purification steps. Evaporation (EV) followed by ethanol precipitation (P) and freeze-drying (FD), gave a yield in hemicellulosic powder of 36.5% (dry weight of powder/dry weight of extract after liquid/solid separation) with a total sugar content equal to 48.4% but also used a large amount of ethanol. The other studied purification process was based on a combination of ultrafiltration (UF), anion exchange chromatography (CHR) and spray-drying (SD). It gave a yield in hemicellulosic powders of 24.6% and a total sugar content equal to 28.7%. The technical performances of the second process appear to be less attractive but with a lower energetic and ethanol consumption. Thus secondly the environmental impacts (water consumption and CO₂ emission) of the ultrafiltration step were quantified. Life Cycle Assessment data (Ecoinvent) were used to convert materials used for the infrastructure and energy consumed during functioning into carbon dioxide emissions and water consumptions. Results have shown that environmental impacts due to the operating conditions are higher than those relative to raw material involved in the installation. The study showed that this kind of approach allows the determination of optimum conditions for the ultrafiltration step.