Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium

Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, while approximately one third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.

Life Cycle Assessment guidelines for the sustainable production and recycling of aggregates:The Sustainable Aggregates Resource Management project (SARMa)

The mining/quarrying industry is a sector of industry where there are very few Life Cycle Assessment (LCA) tools, and where the role of LCA has been poorly investigated. A key issue is the integration of three inter-dependent life cycles: Project, Asset and Product. Given the unique features of mining LCAs, this Note from the Field presents a common methodology implemented within the Sustainable Aggregates Resource Management (SARMa) Project (www.sarmaproject.eu) in order to boost adoption of LCA in the aggregate industry in South Eastern Europe. The proposed methodology emphasises the importance of resource efficiency and recycling in the context of a Sustainable Supply Mix of aggregates for the construction industry. Through its adoption, aggregate producers, recyclers, and governmental planners would gain confidence with LCA tools and conduct consistent and meaningful life cycle analyses of natural and recycled aggregates. © 2011 Elsevier Ltd. All rights reserved.

Soil conditioning for EPBMs

Nowadays, the Earth Pressure Balanced (EPB) shields are used more and more caused by both the mechanical development of the machines and the more effective use of additives such as foams and polymers. These additives are used to condition spoil in the screw conveyor. A crucial component of EPB tunnelling applications is ground conditioning. Thus, in order to permit quantitative measurements of the conditioned ground behavior, it is necessary to develop and use a test able to simulate the extraction of earth from the chamber with a screw conveyor. This reliable test procedure can provide quantitative parameters that can really describe the conditioned soil behavior.

Soil Conditioning and Ground Monitoring for Shield Tunnelling

Soil conditioning consists of mixing and remolding the natural material during the mechanical excavation of tunnels, generally at low depth, with additives, in order to obtain suitable properties of plasticity and consistency for the excavated material, so becoming able to apply a counterpressure against natural earth pressure and groundwater flow towards the excavation chamber. The assessment and the control of the soil parameters and of machine performance are fundamental for a regular and safe excavation, also with regards to surface stability. This paper mainly focus on testing approach aimed to the proper soil conditioning with EPB shields, whose results have been validated at real scale. The influence of the water content and the amount of conditioning foam has been studied by the Authors. A proper definition of conditioning parameters can allow to extend the application field of Earth Pressure Balance (EPB) tunnel machines to various grain soil distribution, even in weak rock formations (e.g. siltstone or flysch). Importance of conditioning is reflected also on the possibility of a proper spoil disposal or better for its reuse.

Fetal Umbilical Artery Doppler Pulsatility Index as a Predictor of Cardiovascular Risk Factors in Children - A Long-Term Follow Up Study

Abstract Objective To determine if high umbilical artery Doppler (UAD) pulsatility index (PI) is associated with cardio-vascular (CV) risk-factors in children at age 12 years. Methods We studied 195 children at age 12 years who had had in-utero UAD studies performed at 28 weeks gestation. The children were grouped according to whether their umbilical Doppler PI was high (indicating poor feto-placental circulation) or normal. At age 12 years we assessed CV risk factors, including anthropometric measures, blood pressure, pulse wave velocity (a measure of arterial compliance), cardio-respiratory fitness and homocysteine and cholesterol serum levels. Results Compared with children with a normal UAD PI (N=88), the children (N=107) with high UAD PI had higher resting pulse rate (p=0.04), higher pulse wave velocity (p=0.046), higher serum homocysteine levels (p=0.032) and reduced arterial compliance (7.58 v 8.50 m/sec, p=0.029) using univariate analysis. These differences were not present when adjusting for cofounders was modelled. Conclusion High PI on UAD testing in-utero may be associated with increased likelihood of some cardio-vascular risk factors at age 12-years but confounding variables may be as important. Our study raises possible long-term benefits of in-utero UAD measurements.

Pepsin in bronchoalveolar lavage fluid:a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration

Gastro-oesophageal reflux (GOR)-related aspiration is associated with respiratory disease, but the current "gold standard" investigation, the lipid-laden macrophage index (LLMI), is flawed. A specific marker of GOR-related aspiration should originate in the stomach, but not the lung. An assay to detect gastric pepsin in the bronchoalveolar lavage (BAL) of children was developed and validated.

Nasal Epithelial Cells Can Act as a Physiological Surrogate for Paediatric Asthma Studies

Introduction: Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures.

Methods: Paired nasal and bronchial epithelial cells from asthmatic children (n = 9) were differentiated for 28 days under unstimulated and IL-13-stimulated conditions. Morphological and physiological markers were analysed using immunocytochemistry, transepithelial-electrical-resistance, Quantitative Real-time-PCR, ELISA and multiplex cytokine/chemokine analysis.

Results: Physiologically, nasal epithelial cells from asthmatic children exhibit similar cytokine responses to stimulation with IL-13 compared with paired bronchial epithelial cells. Morphologically however, nasal epithelial cells differed significantly from bronchial epithelial cells from asthmatic patients under unstimulated and IL-13-stimulated conditions. Nasal epithelial cells exhibited lower proliferation/differentiation rates and lower percentages of goblet and ciliated cells when unstimulated, while exhibiting a diminished and varied response to IL-13.

Conclusions: We conclude that morphologically, nasal epithelial cells would not be a suitable surrogate due to a significantly lower rate of proliferation and differentiation of goblet and ciliated cells. Physiologically, nasal epithelial cells respond similarly to exogenous stimulation with IL-13 in cytokine production and could be used as a physiological surrogate in the event that bronchial epithelial cells are not available.

Interventions to prevent steroid-induced osteoporosis and osteoporotic fractures in Duchenne muscular dystrophy (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows:

Primary objective: To assess the effects of interventions to delay or treat osteoporosis in DMD patients treated with glucocorticoid steroids.

Secondary objectives: To assess the effects of interventions to delay or treat osteoporosis in DMD on the frequency of vertebral fragility fractures and long bone fractures in DMD patients treated with glucocorticoid steroids.

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

Aims: To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.

Methods: The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates.

Results: The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation:

TVCL=12.9×(Weight /13.2)^0.75×EXP(-0.00158×TPT)×EXP(0.428×CYP3A5)

where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where*1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h kg (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%.

Conclusion: Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance. © 2013 The British Pharmacological Society.

Parents' experiences of caring for their infant following surgery in the neonatal period: A literature review

Previous research with parents of preterm and low-birth weight infants admitted to the Neonatal Intensive Care Unit (NICU) has indicated the following: (i) parents are at risk of experiencing stress associated with the NICU environment; (ii) parents are at risk of short- and longer-term psychological distress; and (iii) the family is at risk of longer-term stress and strain. However, parents of infants admitted to the NICU for surgery are an under-researched population. This paper provides an overview of the current literature in relation to this issue. The results highlight the paucity of research conducted with parents of infants admitted to the NICU for surgery. A number of gaps and limitations were also identified in the current literature, including a lack of examination why some parents cope better than others, and a focus solely on parents of preterm and low birth weight infants. To conclude, further research with parents of infants who had surgery in the first few weeks of life is needed. Such information could help inform clinicians caring for these infants and their families, and would enable identification of those parents and families most at risk.

Human Parechovirus Infection in Neonatal Intensive Care

Background: Approximately 5-6% of all infective episodes in NICU are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV.

Methods: Blood samples were taken from NICU babies greater than 48 hours old, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5'-untranslated region of the HPeV genome by reverse transcriptase PCR. Results were confirmed by electrophoresis and DNA sequencing.

Results: HPeV was detected in 11 of 84 samples (13%). These infants had a mean (interquartile range, IQR) gestational age of 28.9 (26.9 - 30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11-27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December - February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination.

Conclusions: We found a HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.

In situ electron holography of the dynamic magnetic field emanating from a hard-disk drive writer

The proliferation of mobile devices in society accessing data via the ‘cloud’ is imposing a dramatic increase in the amount of information to be stored on hard disk drives (HDD) used in servers. Forecasts are that areal densities will need to increase by as much as 35% compound per annum and by 2020 cloud storage capacity will be around 7 zettabytes corresponding to areal densities of 2 Tb/in2. This requires increased performance from the magnetic pole of the electromagnetic writer in the read/write head in the HDD. Current state-of-art writing is undertaken by morphologically complex magnetic pole of sub 100 nm dimensions, in an environment of engineered magnetic shields and it needs to deliver strong directional magnetic field to areas on the recording media around 50 nm x 13 nm. This points to the need for a method to perform direct quantitative measurements of the magnetic field generated by the write pole at the nanometer scale. Here we report on the complete in situ quantitative mapping of the magnetic field generated by a functioning write pole in operation using electron holography. Opportunistically, it points the way towards a new nanoscale magnetic field source to further develop in situ Transmission Electron Microscopy.