Concordance for changes in allergic asthma domain variables after short-term corticosteroid therapy.

BACKGROUND: Asthma is a complex syndrome with multiple domains including symptoms, lung function, asthma control, and airway inflammation. A study of Fenom PRO™, a novel monitor for exhaled nitric oxide (FeNO), provided an opportunity to look at concordance/discordance (C/D) for changes in multiple asthma domains over a 2-week period after corticosteroid therapy. METHODS: Non-steroid-treated adults and children with uncontrolled asthma had asthma domain measures, (FeNO), forced expired volume in 1 s (FEV1), the 6-item Asthma Control Questionnaire scores (ACQ6), and daily asthma symptoms, assessed before and after a 2-week course of corticosteroids. Asthma symptoms were assessed using a custom novel twice-daily symptom scale (ASX). C/D bidirectional changes in all domains were calculated around both the zero point, and around the minimal important difference (MID) in relevant subjects. RESULTS: There was a highly significant fall in mean FeNO of 51.7% over 2 weeks (p < 0.0001) accompanied by significant improvements in mean FEV1, ACQ6 and ASX scores. However, C/D between individual domains varied considerably between subjects. The C/D between parameters for any change around zero for the combined adults and pediatric population was best for FeNO and ACQ6, 79.3/20.7% while FEV1 was more discordant than other parameters in general. When considering changes around the minimal important difference (MID) in a subset, the level of concordance increased in general, with FeNO and ACQ6 demonstrating a C/D of 93.5/6.6%. CONCLUSION: This data demonstrates that the concordance between changes in the asthma domains is often substantially less than 100%. Reasons for this may include different time courses for change of the separate domains, the degree of abnormality for each domain at baseline, as well as intrinsic limitations of each parameter.

Clinical precision, accuracy, number and durations of exhalations for a novel electrochemical monitor for exhaled nitric oxide.

BACKGROUND: Exhaled nitric oxide (FeNO) is a validated marker of eosinophilic inflammation. Fenom ProTM is a novel FDA-cleared monitor for FeNO. The American Thoracic Guidelines from 2005 recommend at least 6 s exhalation for adults and in some cases up to 10 s, and 4 s for children, and that the average of the first two valid exhalations is taken as the FeNO value. METHODS: Clinical precision, 6 versus 10 s exhalations, the first versus the average of the first two valid exhalation methods comparison were evaluated for Fenom ProTM, as well as a methods comparison to the NIOX VERO® monitor. RESULTS: The intent-to-treat population (n = 126) consisted of 83 adults, and 43 pediatric subjects with 16 subjects under 12 years of age. Clinical precision for 10 s exhalations on Fenom ProTM was excellent with a within-subject standard deviation (SD) range of 0.57-3.73 ppb and mean coefficient of variation (CV) range of 4.21% to 9.65%. The clinical precision for the separate adult and pediatric groups as well as for the 6 s exhalations were similar. The 10 and 6 s exhalation comparisons and one versus the average of two valid exhalations showed a high level of agreement. The Fenom ProTM and the NIOX VERO® monitors also demonstrated a high level of agreement with the values from the latter slightly lower (mean bias of -3.2 ppb). CONCLUSION: Fenom ProTM demonstrated eminently acceptable performance supporting its clinical utility. The data suggests that 6 s exhalations can be used in adults and children, and that one exhalation is adequate rather than obtaining the average of two exhalations on Fenom ProTM.

Fabrication and characterization of graphitic carbon nanostructures with controllable size, shape, and position.

The incorporation of carbon materials in micro- and nanoscale devices is being widely investigated due to the promise of enhanced functionality. Challenges in the positioning and addressability of carbon nanotubes provide the motivation for the development of new processes to produce nanoscale carbon materials. Here, the fabrication of conducting, nanometer-sized carbon structures using a combination of electron beam lithography (EBL) and carbonisation is reported. EBL is used to directly write predefined nanometer-sized patterns in a thin layer of negative resist in controllable locations. Careful heat treatment results in carbon nanostructures with the size, shape, and location originally defined by EBL. The pyrolysis process results in significant shrinkage of the structures in the vertical direction and minimal loss in the horizontal direction. Characterization of the carbonized material indicates a structure consisting of both amorphous and graphitized carbon with low levels of oxygen. The resistivity of the material is similar to other disordered carbon materials and the resistivity is maintained from the bulk to the nanoscale. This is demonstrated by fabricating a nanoscale structure with predictable resistance. The ability to fabricate these conductive structures with known dimensions and in predefined locations can be exploited for a number of applications. Their use as nanoband electrodes is also demonstrated.

Redox-driven conductance switching via filament formation and dissolution in carbon/molecule/TiO2/Ag molecular electronic junctions.

Carbon/molecule/TiO2/Au molecular electronic junctions show robust conductance switching, in which a metastable high conductance state may be induced by a voltage pulse which results in redox reactions in the molecular and TiO2 layers. When Ag is substituted for Au as the "top contact", dramatically different current/voltage curves and switching behavior result. When the carbon substrate is biased negative, an apparent breakdown occurs, leading to a high conductance state which is stable for at least several hours. Upon scanning to positive bias, the conductance returns to a low state, and the cycle may be repeated hundreds of times. Similar effects are observed when Cu is substituted for Au and for three different molecular layers as well as "control" junctions of the type carbon/TiO2/Ag/Au. The polarity of the "switching" is reversed when the Ag layer is between the carbon and molecular layers, and the conductance change is suppressed at low temperature. Pulse experiments show very erratic transitions between high and low conductivity states, particularly near the switching threshold. The results are consistent with a switching mechanism based on Ag or Cu oxidation, transport of their ions through the TiO2, and reduction at the carbon to form a metal filament.

Covalent bonding of alkene and alkyne reagents to graphitic carbon surfaces.

Various aromatic and aliphatic alkynes and one alkene were covalently bonded to sp(2)-hybridized carbon surfaces by heat treatment in an argon atmosphere. X-ray photoelectron spectroscopy, Raman, and FTIR spectra of the modified surfaces showed that the molecules were intact after the 400 degrees C heat treatment but that the alkyne group had reacted with the surface to form a covalent bond. Alkynes with ferrocene and porphyrin centers exhibited chemically reversible voltammetric waves that could be cycled many times. Atomic force microscopy of the modified surfaces indicated a thickness of the molecular layer consistent with monolayer coverage, and surface coverage determined by voltammetry was also in the monolayer range. Raman spectroscopy of the porphyrin monolayers formed from a porphyrin alkyne showed no evidence for dimer formation, although multilayer formation may occur at undetected levels. FTIR spectra of the porphyrin-modified carbon surfaces were well-defined, similar to the parent molecule, and indicative of an average tilt angle between the porphyrin plane and the surface normal of 37 degrees . The bond between the molecular monolayer and the carbon surface was quite stable, withstanding sonication in tetrahydrofuran, mild aqueous acid and base, and repeated voltammetric cycling in propylene carbonate electrolyte. Heat treatment of alkynes and alkenes appears to be a generally useful method for modifying carbon surfaces, which can be applied to both aromatic and aliphatic molecules.

A glassy carbon microfluidic device for electrospray mass spectrometry.

Due to the broad impact of microfabrication technology on chemistry and biology, new methods to pattern and etch a variety of materials are being explored in a number of laboratories. Here, we report the design, fabrication, and operation of a glassy carbon (GC) microchip interfaced to a nanoelectrospray ionization source and a quadrupole mass spectrometer. The method involves standard photolithographic pattern transfer to a photoresist layer and anodization of the exposed GC substrate in basic electrolyte to produce a series of channels with well-defined wall structure. The performance of the microchip was evaluated with standard polymer and peptide samples.