Aerosol-phase activity of iodine captured from a triiodide resin filter on fine particles containing an infectious virus.

AIMS: To avoid interference by water-iodine disinfection chemistry and measure directly the effect of iodine, captured from a triiodide complex bound to a filter medium, on viability of penetrating viral particles. METHODS AND RESULTS: Aerosols of MS2 coli phage were passed through control P100 or iodinated High-Efficiency Particulate Air media, collected in plastic bags, incubated for 0-10 min, collected in an impinger containing thiosulphate to consume all unreacted iodine, plated and enumerated. Comparison of viable counts demonstrated antimicrobial activity with an apparent half-life for devitalization in tens of seconds; rate of kill decreased at low humidity and free iodine was captured by the bags. CONCLUSIONS: The results support the mechanism of near-contact capture earlier proposed; however, the disinfection chemistry in the aerosol phase is very slow on the time scale of inhalation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that disinfection by filter-bound iodine in the aerosol phase is too slow to be clinically significant in individual respiratory protection, but that it might be of benefit to limit airborne transmission of infections in enclosed areas.

A combined segmenting and non-segmenting approach to signal quality estimation for ambulatory photoplethysmography.

Continuous cardiac monitoring of healthy and unhealthy patients can help us understand the progression of heart disease and enable early treatment. Optical pulse sensing is an excellent candidate for continuous mobile monitoring of cardiovascular health indicators, but optical pulse signals are susceptible to corruption from a number of noise sources, including motion artifact. Therefore, before higher-level health indicators can be reliably computed, corrupted data must be separated from valid data. This is an especially difficult task in the presence of artifact caused by ambulation (e.g. walking or jogging), which shares significant spectral energy with the true pulsatile signal. In this manuscript, we present a machine-learning-based system for automated estimation of signal quality of optical pulse signals that performs well in the presence of periodic artifact. We hypothesized that signal processing methods that identified individual heart beats (segmenting approaches) would be more error-prone than methods that did not (non-segmenting approaches) when applied to data contaminated by periodic artifact. We further hypothesized that a fusion of segmenting and non-segmenting approaches would outperform either approach alone. Therefore, we developed a novel non-segmenting approach to signal quality estimation that we then utilized in combination with a traditional segmenting approach. Using this system we were able to robustly detect differences in signal quality as labeled by expert human raters (Pearson's r = 0.9263). We then validated our original hypotheses by demonstrating that our non-segmenting approach outperformed the segmenting approach in the presence of contaminated signal, and that the combined system outperformed either individually. Lastly, as an example, we demonstrated the utility of our signal quality estimation system in evaluating the trustworthiness of heart rate measurements derived from optical pulse signals.

Standard method for deposition of dry, aerosolized, silica-coated Bacillus spores onto inanimate surfaces.

AIMS: To evaluate a standard aerosolization method for uniformly depositing threat-representative spores onto surfaces. METHODS AND RESULTS: Lyophilized Bacillus anthracis ΔSterne spores, coated in silica, were aerosolized into a containment chamber and deposited onto nine surface types by two independent laboratories. Laboratory A produced a mean loading concentration of 1·78 × 10(5) CFU cm(-2) ; coefficient of variation (CV) was <40% for 96% of samples. Laboratory B produced a mean loading concentration of 7·82 × 10(6) CFU cm(-2) ; 68% of samples demonstrated CV <40%. CONCLUSIONS: This method has been shown to meet the goal of loading threat-representative spores onto surfaces with low variability at concentrations relevant to the Department of Defense. SIGNIFICANCE AND IMPACT OF THE STUDY: As demonstrated in 2001, a biological attack using anthrax disseminated as a dry powder is a credible threat. This method will provide a means to load spores onto surfaces that mimic a 'real-world' scenario of an aerosolized anthrax attack. The method has utility for evaluating sporicidal technologies and for nondecontamination studies, for example fate and transport or reaerosolization.

Direct electrical stimulation of the somatosensory cortex in humans using electrocorticography electrodes: a qualitative and quantitative report.

OBJECTIVE: Recently, electrocorticography-based brain-computer interfaces have been successfully used to translate cortical activity into control signals for external devices. However, the utility of such devices would be greatly enhanced by somatosensory feedback. Direct stimulation of somatosensory cortex evokes sensory perceptions, and is thus a promising option for closing the loop. Before this can be implemented in humans it is necessary to evaluate how changes in stimulus parameters are perceived and the extent to which they can be discriminated. APPROACH: Electrical stimulation was delivered to the somatosensory cortex of human subjects implanted with electrocorticography grids. Subjects were asked to discriminate between stimuli of different frequency and amplitude as well as to report the qualitative sensations elicited by the stimulation. MAIN RESULTS: In this study we show that in humans implanted with electrocorticography grids, variations in the amplitude or frequency of cortical electrical stimulation produce graded variations in percepts. Subjects were able to reliably distinguish between different stimuli. SIGNIFICANCE: These results indicate that direct cortical stimulation is a feasible option for sensory feedback with brain-computer interface devices.

Design, construction and validation of a nose-only inhalation exposure system to measure infectivity of filtered bioaerosols in mice.

AIMS: The aim of this project was to validate a method to deliver a reproducible, selected dose of infective bioaerosol through a respiratory protective technology to an animal that exhibits a proportional clinical response. METHODS AND RESULTS: The Controlled Aerosol Test System (CATS) was designed to generate and condition a viable infective aerosol, pass it through a treatment technology and thence to the breathing zone of a mouse constrained in a Nose-Only Inhalation Exposure System (NOIES). A scanning mobility particle sizer and impingers at sampling ports were used to show that viability is preserved and particle size distribution (PSD) is acceptably uniform throughout the open CATS, including the 12 ports of the NOIES, and that a particle filter used caused the expected attenuation of particle counts. CONCLUSIONS: Controlled Aerosol Test System delivers uniformly to mice constrained in the NOIES a selectable dose of viral bioaerosol whose PSD and viable counts remain consistent for an hour. SIGNIFICANCE AND IMPACT OF THE STUDY: This study's characterization of CATS provides a new test system in which a susceptible small-animal model can be used as the detector in a quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol. This provides a major improvement over the use of viable bioaerosol collectors (e.g. impactors and impingers), which provide data that are difficult to relate to the attenuation of pathogenicity.

Proportional mouse model for aerosol infection by influenza.

AIMS: The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen - influenza A/PR/8/34 (H1N1) virus - using a small-animal model in the Controlled Aerosol Test System (CATS). METHODS AND RESULTS: Intranasal inoculation of nonadapted H1N1 virus into C57BL, BALB/c and CD-1 mice caused infection in all three species. Respiratory exposure of CD-1 mice to the aerosolized virus at graduated doses was accomplished in a modified rodent exposure apparatus. Weight change was recorded for 7 days postexposure, and viral populations in lung tissue homogenates were measured post mortem by DNA amplification (qRT-PCR), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of PCR cycle threshold vs delivered dose were linear to threshold doses of ~40 TCID(50) and ~12 TCID(50) , respectively. CONCLUSIONS: MID(50) for inspired H1N1 aerosols in CD-1 mice is between 12 and 40 TCID(50) ; proportionality to dose of weight loss and viral populations makes the CD-1 mouse a useful model for measuring infectivity by inhalation. SIGNIFICANCE AND IMPACT OF THE STUDY: In the CATS, this mouse-virus model provides the first quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol.

Analysis of residual chemicals on filtering facepiece respirators after decontamination.

The N95 filtering facepiece respirator (FFR) is commonly used to protect individuals from infectious aerosols. Health care experts predict a shortage of N95 FFRs if a severe pandemic occurs, and an option that has been suggested for mitigating such an FFR shortage is to decontaminate and reuse the devices. Before the effectiveness of this strategy can be established, many parameters affecting respiratory protection must be measured: biocidal efficacy of the decontamination treatment, filtration performance, pressure drop, fit, and toxicity to the end user post treatment. This research effort measured the amount of residual chemicals created or deposited on six models of FFRs following treatment by each of 7 simple decontamination technologies. Measured amounts of decontaminants retained by the FFRs treated with chemical disinfectants were small enough that exposure to wearers will be below the permissible exposure limit (PEL). Toxic by-products were also evaluated, and two suspected toxins were detected after ethylene oxide treatment of FFR rubber straps. The results provide encouragement to efforts promoting the evolution of effective strategies for decontamination and reuse of FFRs.

The Dry Aerosol Deposition Device (DADD): an instrument for depositing microbial aerosols onto surfaces.

Concerns surrounding the contamination of infrastructure and equipment with biowarfare agents have led to the development of antimicrobial surfaces/coatings that are designed to "self-sterilize." Surfaces will likely be contaminated via an aerosol exposure and thus antimicrobial efficacy measurements should also be performed using biological aerosols. Standard methods that use microbial agents suspended in aqueous buffers may provide misleading results that overestimate the performance of the surface. A settling chamber is the most common instrument for applying biological aerosols to surfaces. However, settling chambers have some drawbacks (e.g., slow loading times, large footprint, variable loading, etc.) that make them undesirable for many applications. We have developed a Dry Aerosol Deposition Device (DADD) that uses impaction rather than settling to load surfaces with biological aerosols. The use of impaction allows for rapid and highly reproducible loading of microorganisms onto surfaces. We have demonstrated that the DADD can deliver both Bacillus atrophaeus spores and Staphylococcus aureus vegetative cells to glass coupons at concentrations exceeding 1x10(4) CFU/cm(2). The average coefficient of variation (CV) for sample-to-sample loading within an experiment was 13.6% for spores and 6.1% for S. aureus cells. The DADD is also a relatively simple and inexpensive device that can easily be contained within a 4-foot biological safety cabinet.

Antioxidants in neoplastic cells: IV. Evidence that the phenolic antioxidant A274 is 9-(4-hydroxyphenyl)xanthene, an artifact in tissue culture media.

An extensively conjugated phenol (A274), recently shown to be present as a common trace constituent in randomly selected batches of commercial tissue culture media, was diazomethylated; the monomethyl derivative so prepared was shown to exhibit gas chromatographic and mass spectrometric properties identical to those observed for synthetically prepared 9-(4-methoxyphenyl)xanthene, but different from those of several isomeric compounds. The structure 9-(4-hydroxyphenyl)xanthene is thus proposed for A274.

Chemical ionization mass spectra of phenothiazine derivatives and their oxygenated analogs.

Twenty-nine derivatives of phenothiazine formed relatively stable ions by proton capture under conditions of chemical ionization, using methane or isobutane as reagent gas. Fragments of generally low abundance formed by simple bond cleavage in the trimethylene portion of the side chain and by loss of water or hydrogen halide. Mass spectra obtained from pyrolyzates of amine salts and from the corresponding free bases were essentially identical.

Quantitation of glycine in plasma and urine by chemical ionization mass fragmentography.

A new technique has been developed for rapid and precise quantitation of glycine in micro samples of biological fluids. Glycine is measured as the n-butyl N-trifluoroacetyl (TAB) derivative by chemical ionization mass fragmentography, using both methane and isobutane as carrier/reagent gases, with the analogous derivative of 2,2-dideuterioglycine added as the internal standard. This technique is also readily applicable, with sensitivity to the femtomole level, to determinations of other amino acids, as, for example, in studies of congenital errors of metabolism.

Quantitative, multicomponent analysis of fatty acids from cholesteryl esters by chemical ionization reconstructed mass chromatography.

Reconstructed mass chromatography using methane as a carrier and reagent gas for chemical ionization gas chromatography-mass spectrometry of the derived methyl esters allows rapid, quantitative microdeterminations of complete cholesteryl ester fatty acid profiles. The sensitivity of this method is consistent with completely specific, multicomponent assay at the picomole level. Introduction of two homologues as internal standards, one into the intact biological specimen and the other after derivatization, provides a measure of the net efficiency of the processes of extraction and derivatization. This procedure may be extended readily to the determination of fatty acid profiles in most biological fluids.