Exhaled nitric oxide correlates with airway eosinophils in childhood asthma

Background: Exhaled nitric oxide has been proposed as a marker for airway inflammation in asthma. The aim of this study was to compare exhaled nitric oxide levels with inflammatory cells and mediators in bronchoalveolar lavage fluid from asthmatic and normal children.

Methods: Children were recruited from elective surgical lists and a non-bronchoscopic bronchoalveolar lavage (BAL) was performed after induction of anaesthesia. Exhaled nitric oxide (parts per billion) was measured by two techniques: tidal breathing and restricted breath.

Results: Median (interquartile range) exhaled nitric oxide measured by restricted breath was increased in asthmatics compared with normal children (24.3 (10.5–66.5) v 9.7 (6.5–16.5), difference between medians 14.6 (95% CI 5.1 to 29.9), p=0.001). In asthmatic children exhaled nitric oxide correlated significantly with percentage eosinophils (r=0.78, p<0.001 (tidal breathing) and r=0.78, p<0.001 (restricted breath)) and with eosinophilic cationic protein (r=0.53, p<0.01 restricted breath)), but not with other inflammatory cells in the BAL fluid. The area under the receiver operator characteristic curves for the prediction of the presence of eosinophilic airways inflammation by exhaled nitric oxide (tidal and restricted) was 0.80 and 0.87, respectively.

Conclusions: Exhaled nitric oxide correlates closely with percentage eosinophils in BAL fluid in asthmatic children and is therefore likely to be a useful non-invasive marker of airway inflammation.

The validity of a latent class typology of adolescent drinking patterns

Objectives: This study examined the validity of a latent class typology of adolescent drinking based on four alcohol dimensions; frequency of drinking, quantity consumed, frequency of binge drinking and the number of alcohol related problems encountered. Method: Data used were from the 1970 British Cohort Study sixteen-year-old follow-up. Partial or complete responses to the selected alcohol measures were provided by 6,516 cohort members. The data were collected via a series of postal questionnaires. Results: A five class LCA typology was constructed. Around 12% of the sample were classified as �hazardous drinkers� reporting frequent drinking, high levels of alcohol consumed, frequent binge drinking and multiple alcohol related problems. Multinomial logistic regression, with multiple imputation for missing data, was used to assess the covariates of adolescent drinking patterns. Hazardous drinking was associated with being white, being male, having heavy drinking parents (in particular fathers), smoking, illicit drug use, and minor and violent offending behaviour. Non-significant associations were found between drinking patterns and general mental health and attention deficient disorder. Conclusion: The latent class typology exhibited concurrent validity in terms of its ability to distinguish respondents across a number of alcohol and non-alcohol indicators. Notwithstanding a number of limitations, latent class analysis offers an alternative data reduction method for the construction of drinking typologies that addresses known weaknesses inherent in more tradition classification methods.

Incretin hormone mimetics and analogues in diabetes therapeutics

The incretin hormones glucagon-like peptide-I (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. Incretin analogues/mimetics activate GLP-I or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1 analogue suitable for once-daily administration, are ongoing. A number of other incretin molecules are at earlier stages of development. This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists.

Synthesis of a neodymium-quinolate complex for near-infrared electroluminescence applications

A structurally pure, near-infrared emissive Nd-(5,7-dichloro-8-hydroxyquinoline)4 tetrakis complex has been synthesized. When incorporated as a dopant in the blue emissive, hole conducting polymer poly(N-vinylcarbazole), PVK, sensitized neodymium ion emission was observed following photo-excitation of the polymer host. OLED devices were fabricated by spin-casting layers of the doped polymer onto glass/indium tin oxide (ITO)/3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates. An external quantum efficiency of 1 x 10(-3)% and a near-infrared irradiance of 2.0 nW/mm(2) at 25 mA/mm(2) and 20 V was achieved using glass/ITO/PEDOT/ PVK:Nd-(5,7-dichloro-8-hydroxyquinoline)(4)/Ca/Al devices. (C) 2007 Elsevier B.V. All rights reserved.

An experiment for two-color photoionization using high intensity extreme-UNT free electron and near-IR laser pulses

We describe an experimental system designed for single-shot photoelectron spectroscopy on free atoms and molecules at the Free Electron Laser in Hamburg (FLASH at DESY). The combination of the extreme ultra-violet (EUV) Free Electron Laser and a temporally synchronized optical fs laser (Ti:Sapphire) enables a variety of two-color pump-probe experiments. The spectral, temporal and spatial characteristics of both the EUV FEL and the optical laser pulses, the experimental procedure to control their overlap as well as the performance of an electron spectrometer used to obtain single-shot photoelectron spectra are discussed. As an illustration of the capabilities of this set-up, some results on two-photon two-color ionization of rare gases are presented. (c) 2007 Elsevier B.V. All rights reserved.

Cost function adaptation: a stochastic gradient algorithm for data echo cancellation

A family of stochastic gradient algorithms and their behaviour in the data echo cancellation work platform are presented. The cost function adaptation algorithms use an error exponent update strategy based on an absolute error mapping, which is updated at every iteration. The quadratic and nonquadratic cost functions are special cases of the new family. Several possible realisations are introduced using these approaches. The noisy error problem is discussed and the digital recursive filter estimator is proposed. The simulation outcomes confirm the effectiveness of the proposed family of algorithms.

Nitric oxide synthase gene therapy enhances the toxicity of cisplatin in cancer cells

BACKGROUND AIMS: Cell-based gene therapy is an alternative to viral and non-viral gene therapy. Emerging evidence suggests that mesenchymal stem cells (MSC) are able to migrate to sites of tissue injury and have immunosuppressive properties that may be useful in targeted gene therapy for sustained specific tissue engraftment. METHODS: In this study, we injected intravenously (i.v.) 1x10(6) MSC, isolated from green fluorescent protein (GFP) transgenic rats, into Rif-1 fibrosarcoma-bearing C3H/HeN mice. The MSC had been infected using a lentiviral vector to express stably the luciferase reporter gene (MSC-GFP-luci). An in vivo imaging system (IVIS 200) and Western blotting techniques were used to detect the distribution of MSC-GFP-luci in tumor-bearing animals. RESULTS: We observed that xenogenic MSC selectively migrated to the tumor site, proliferated and expressed the exogenous gene in subcutaneous fibrosarcoma transplants. No MSC distribution was detected in other organs, such as the liver, spleen, colon and kidney. We further showed that the FGF2/FGFR pathways may play a role in the directional movement of MSC to the Rif-1 fibrosarcoma. We performed in vitro co-culture and in vivo tumor growth analysis, showing that MSC did not affect the proliferation of Rif-1 cells and fibrosarcoma growth compared with an untreated control group. Finally, we demonstrated that the xenogenic MSC stably expressing inducible nitric oxide synthase (iNOS) protein transferred by a lentivirus-based system had a significant inhibitory effect on the growth of Rif-1 tumors compared with MSC alone and the non-treatment control group. CONCLUSIONS: iNOS delivered by genetically modified iNOS-MSC showed a significant anti-tumor effect both in vitro and in vivo. MSC may be used as a target gene delivery vehicle for the treatment of fibrosarcoma and other tumors

Ionography of Submicron Foils and Nanostructures Using Ion Flow Generated in FS-Laser Cluster Plasma

A novel type of submicron ion radiography designed to image low-contrast objects, including nanofoils, membranes and biological structures, is proposed. It is based on femtosecond-laser-driven-cluster- plasma source of multicharged ions and polymer dosimeter film CR-39. The intense isotropic ion flow was produced by femtosecond Ti:Sa laser pulses with intensity similar to 4x10(17) W/cm(2) absorbed in the supersonic jet of the mixed He and CO2 gases. Two Focusing Spectrometers with Spatial Resolution (FSSR) were used to measure X-ray spectra of H-and He-like multicharged oxygen ions. The spectra testify that ions with energy more than 300 keV were radiated in different directions from the plasma source. High contrast ion radiography images were obtained for 2000 dpi metal mesh, 1 mu m polypropylene and 100 nm Zr foils as well as for the different biological objects. Images were recorded on a 1 mm thick CR-39 detector, placed in contact with back surface of the imaged samples at the distances 140 -160 mm from the ion source. The spatial resolution of the image no worse than 600 nm was provided. A difference in object thickness of 100 nm was very well resolved for both Zr and polymer foils. The ion radiography images recorded at different angles from the source, demonstrated almost uniform spatial distribution of ion with total number of 10(8) per shot. (C) 2009 WILEY-VCH Vertag GmbH & Co. KGaA, Weinheim

Mixed Religion Schools in NI and Israel

This paper compares the concept of mixed faith/cultural education in Northern Ireland and Israel. It is primarily concerned with the processes that these 'integrated' schools adopt in their quest to improve relations between divided ethnic groups. Drawing on qualitative data collected in two mixed religion primary schools in each jurisdiction the paper shows that the schools' existing cultural norms act as important mediating influences on the way that inter-group relationships are constructed. The paper concludes that attention needs to be paid to both the policy context and the culture if contact initiatives are to be successful.