Continuous-wave cavity ringdown for high-sensitivity polarimetry and magnetometry measurements.

We report the development of a novel variant of cavity ringdown polarimetry using a continuous-wave laser operating at 532 nm for highly precise chiroptical activity and magnetometry measurements. The key methodology of the apparatus relies upon the external modulation of the laser frequency at the frequency splitting between non-degenerate left- and right-circularly polarized cavity modes. The method is demonstrated by the evaluation of the Verdet constants of crystalline CeF3 and fused silica, in addition to the observation of gas- and solution-phase optical rotations of selected chiral molecules. Specifically, optical rotations of (i) vapors of α-pinene and R-(+)-limonene, (ii) mutarotating D-glucose in water, and (iii) acidified L-histidine solutions are determined. The detection sensitivities for the gas- and solution-phase chiral activity measurements are ∼30 and ∼120µdeg over a 30 s detection period per cavity round trip pass, respectively. Furthermore, the measured optical rotations for R-(+)-limonene are compared with computations performed using the TURBOMOLE quantum chemistry package. The experimentally observed optically rotatory dispersion of this cyclic monoterpene was thus rationalized via a consideration of its room temperature conformer distribution as determined by the aforementioned single-point energy calculations.

Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis.

This study explored the use of computed cardiopulmonography (CCP) to assess lung function in early-stage cystic fibrosis (CF). CCP has two components. The first is a particularly accurate technique for measuring gas exchange. The second is a computational cardiopulmonary model where patient-specific parameters can be estimated from the measurements of gas exchange. Twenty-five participants (14 healthy controls, 11 early-stage CF) were studied with CCP. They were also studied with a standard clinical protocol to measure the lung clearance index (LCI2.5). Ventilation inhomogeneity, as quantified through CCP parameter σlnCl, was significantly greater (P < 0.005) in CF than in controls, and anatomical deadspace relative to predicted functional residual capacity (DS/FRCpred) was significantly more variable (P < 0.002). Participant-specific parameters were used with the CCP model to calculate idealized values for LCI2.5 (iLCI2.5) where extrapulmonary influences on the LCI2.5, such as breathing pattern, had all been standardized. Both LCI2.5 and iLCI2.5 distinguished clearly between CF and control participants. LCI2.5 values were mostly higher than iLCI2.5 values in a manner dependent on the participant's respiratory rate (r = 0.46, P < 0.05). The within-participant reproducibility for iLCI2.5 appeared better than for LCI2.5, but this did not reach statistical significance (F ratio = 2.2, P = 0.056). Both a sensitivity analysis on iLCI2.5 and a regression analysis on LCI2.5 revealed that these depended primarily on an interactive term between CCP parameters of the form σlnCL*(DS/FRC). In conclusion, the LCI2.5 (or iLCI2.5) probably reflects an amalgam of different underlying lung changes in early-stage CF that would require a multiparameter approach, such as potentially CCP, to resolve.NEW & NOTEWORTHY Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulmonary model that is used to identify a set of patient-specific characteristics of the lung. Here, we show that this technique can improve on a standard clinical approach for lung function testing in cystic fibrosis. Most particularly, an approach incorporating multiple model parameters can potentially separate different aspects of pathological change in this disease.

The Lognormal Lung: A new approach to quantifying lung inhomogeneity in COPD.

Early diagnosis and disease phenotyping in COPD are currently limited by the use of spirometry, which may remain normal despite significant small-airways disease and which may not fully capture a patient's underlying pathophysiology. In this study we explored the use of a new non-invasive technique that assesses gas-exchange inhomogeneity in patients with COPD of varying disease severity (according to GOLD Stage), compared with age-matched healthy controls. The technique, which combines highly accurate measurement of respiratory gas exchange using a bespoke molecular flow sensor and a mechanistic mathematical model of the lung, provides new indices of lung function: the parameters σCL, σCd, and σVD represent the standard deviations of distributions for alveolar compliance, anatomical deadspace and vascular conductance relative to lung volume, respectively. It also provides parameter estimates for total anatomical deadspace and functional residual capacity (FRC). We demonstrate that these parameters are robust and sensitive, and that they can distinguish between healthy individuals and those with mild-moderate COPD (stage 1-2), as well as distinguish between mild-moderate COPD (stage 1-2) and more severe (stage 3-4) COPD. In particular, σCL, a measure of unevenness in lung inflation/deflation, could represent a more sensitive non-invasive marker of early or mild COPD. In addition, by providing a multi-dimensional assessment of lung physiology, this technique may also give insight into the underlying pathophysiological phenotype for individual patients. These preliminary results warrant further investigation in larger clinical research studies, including interventional trials.

Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.

Thoracic ultrasound for TB diagnosis in adults and children.

Thoracic ultrasound is an appealing alternative to chest radiography for the diagnosis of TB. Based on research experience conducting thoracic ultrasound for adults and children in South Africa, three key considerations for potential scale-up were identified. First, thoracic ultrasound requires a comprehensive training programme for novice users; artificial intelligence may be used to simplify training and interpretation. Second, a robust ultrasound device is needed with good subpleural resolution and a probe suitable for children. Third, comprehensive scanning of the lungs is time-intensive, and shorter scanning protocols may be more feasible in clinical practice.

L'échographie thoracique est une alternative attrayante à la radiographie pulmonaire pour le diagnostic de la TB. En prenant appui sur l'expérience acquise lors d'études ayant utilisé l'échographie thoracique chez l'adulte et l'enfant en Afrique du Sud, trois considérations clés pour une éventuelle utilisation accrue de cet outil ont été identifiées. Premièrement, tout nouvel utilisateur d'un échographe thoracique doit suivre un programme de formation exhaustif. L'intelligence artificielle pourrait être utilisée pour simplifier la formation et l'interprétation des résultats. Deuxièmement, un échographe de qualité est nécessaire, avec une bonne résolution sous-pleurale et une sonde adaptée à l'enfant. Troisièmement, une scannographie exhaustive des poumons est chronophage ; des protocoles de scannographie plus courts pourraient être plus faciles en pratique clinique.

Determining Water Transport Kinetics in Limestone by Dual-Wavelength Cavity Ring-Down Spectroscopy.

Water plays a major role in the deterioration of porous building materials such as those widely found in built heritage, influencing many physical, chemical, and biological decay processes. This article details a proof-of-principle study using near-infrared cavity ring-down spectroscopy (CRDS) to monitor the release of water and its artificially enriched isotopologues from small (ca. 25 × 25 × 5 mm) samples of limestone subject to drying by a fixed flow of nitrogen with varying levels of humidity and at room temperature and atmospheric pressure. Under low-humidity conditions, the drying kinetics are consistent with the well-established two-phase drying process exhibited by porous materials, namely, an initial constant drying rate period (phase I) followed by a falling drying rate period (phase II). The water diffusivity during phase II, DII, was measured (for Clipsham limestone) to be 3.0 × 10-9 ± 1 × 10-10 m2 s-1. The CRDS measurements allow spectroscopic determination of the total mass of water released by the sample, and the calculated values are in excellent agreement with gravimetric analysis. Importantly, the selectivity and sensitivity afforded by CRDS allows isotope analysis to be carried out, such that the flux of isotopically labeled water out of the sample can be determined under conditions of humidified flow where there may be a simultaneous ingress of water from the environment. Dual-wavelength CRDS distinguishes isotopic species, and it is demonstrated that the drying kinetics and physical properties of the samples are self-consistent when monitoring both HDO and H2O (for HDO, DII was 3.2 × 10-9 ± 4 × 10-10 m2 s-1). As the humidity levels in the flow increase, a departure from the distinct two-phase behavior is observed in the HDO drying curves. These new measurements of isotopically resolved mass fluxes will help refine models for drying mechanisms in porous media.

High performance continuous-wave laser cavity enhanced polarimetry using RF-induced linewidth broadening.

We present precise optical rotation measurements of gaseous chiral samples using near-IR continuous-wave cavity-enhanced polarimetry. Optical rotation is determined by comparing cavity ring-down signals for two counter-propagating beams of orthogonal polarisation which are subject to polarisation rotation by the presence of both an optically active sample and a magneto-optic crystal. A broadband RF noise source applied to the laser drive current is used to tune the laser linewidth and optimise the polarimeter, and this noise-induced laser linewidth is quantified using self-heterodyne beat-note detection. We demonstrate the optical rotation measurement of gas phase samples of enantiomers of α-pinene and limonene with an optimum detection precision of 10 µdeg per cavity pass and an uncertainty in the specific rotation of ∼0.1 deg dm-1 (g/ml)-1 and determine the specific rotation parameters at 730 nm, for (+)- and (-)-α-pinene to be 32.10 ± 0.13 and -32.21 ± 0.11 deg dm-1 (g/ml)-1, respectively. Measurements of both a pure R-(+)-limonene sample and a non-racemic mixture of limonene of unknown enantiomeric excess are also presented, illustrating the utility of the technique.

Diverse clinical and social circumstances: developing patient-centred care for DR-TB patients in South Africa.

OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.

OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.

Time-resolved observations of vibrationally excited NO X 2Π (v') formed from collisional quenching of NO A 2Σ+ (v = 0) by NO X 2Π: evidence for the participation of the NO a 4Π state.

Time-resolved observations have been made of the formation of vibrationally excited NO X 2Π (v') following collisional quenching of NO A 2Σ+ (v = 0) by NO X 2Π (v = 0). Two time scales are observed, namely a fast production rate consistent with direct formation from the quenching of the electronically excited NO A state, together with a slow component, the magnitude and rate of formation of which depend upon NO pressure. A reservoir state formed by quenching of NO A 2Σ+ (v = 0) is invoked to explain the observations, and the available evidence points to this state being the first electronically excited state of NO, a 4Π. The rate constant for quenching of the a 4Π state to levels v' = 11-16 by NO is measured as (8.80 ± 1.1) × 10-11 cm3 molecule-1 s-1 at 298 K where the error quoted is two standard deviations, and from measurements of the increased formation of high vibrational levels of NO(X) by the slow process we estimate a lower limit for the fraction of self-quenching collisions of NO A 2Σ+ (v = 0) which lead to NO a 4Π as 19%.

Pulmonary Effects of Sustained Periods of High-G Acceleration Relevant to Suborbital Spaceflight.

AbstractBACKGROUND: Members of the public will soon be taking commercial suborbital spaceflights with significant Gx (chest-to-back) acceleration potentially reaching up to 6 Gx. Pulmonary physiology is gravity-dependent and is likely to be affected, which may have clinical implications for medically susceptible individuals.METHODS: During 2-min centrifuge exposures ranging up to 6 Gx, 11 healthy subjects were studied using advanced respiratory techniques. These sustained exposures were intended to allow characterization of the underlying pulmonary response and did not replicate actual suborbital G profiles. Regional distribution of ventilation in the lungs was determined using electrical impedance tomography. Neural respiratory drive (from diaphragm electromyography) and work of breathing (from transdiaphragmatic pressures) were obtained via nasoesophageal catheters. Arterial blood gases were measured in a subset of subjects. Measurements were conducted while breathing air and breathing 15 oxygen to simulate anticipated cabin pressurization conditions.RESULTS: Acceleration caused hypoxemia that worsened with increasing magnitude and duration of Gx. Minimum arterial oxygen saturation at 6 Gx was 86 1 breathing air and 79 1 breathing 15 oxygen. With increasing Gx the alveolar-arterial (A-a) oxygen gradient widened progressively and the relative distribution of ventilation reversed from posterior to anterior lung regions with substantial gas-trapping anteriorly. Severe breathlessness accompanied large progressive increases in work of breathing and neural respiratory drive.DISCUSSION: Sustained high-G acceleration at magnitudes relevant to suborbital flight profoundly affects respiratory physiology. These effects may become clinically important in the most medically susceptible passengers, in whom the potential role of centrifuge-based preflight evaluation requires further investigation.Pollock RD, Jolley CJ, Abid N, Couper JH, Estrada-Petrocelli L, Hodkinson PD, Leonhardt S, Mago-Elliott S, Menden T, Rafferty G, Richmond G, Robbins PA, Ritchie GAD, Segal MJ, Stevenson AT, Tank HD, Smith TG. Pulmonary effects of sustained periods of high-G acceleration relevant to suborbital spaceflight. Aerosp Med Hum Perform. 2021; 92(7):633641.

The differing physiology of nitrogen and tracer gas multiple-breath washout techniques.

BACKGROUND: Multiple-breath washout techniques are increasingly used to assess lung function. The principal statistic obtained is the lung clearance index (LCI), but values obtained for LCI using the nitrogen (N2)-washout technique are higher than those obtained using an exogenous tracer gas such as sulfur hexafluoride. This study explored whether the pure oxygen (O2) used for the N2 washout could underlie these higher values. METHODS: A model of a homogenous, reciprocally ventilated acinus was constructed. Perfusion was kept constant, and ventilation adjusted by varying the swept volume during the breathing cycle. The blood supplying the acinus had a standard mixed-venous composition. Carbon dioxide and O2 exchange between the blood and acinar gas proceeded to equilibrium. The model was initialised with either air or air plus tracer gas as the inspirate. Washouts were conducted with pure O2 for the N2 washout or with air for the tracer gas washout. RESULTS: At normal ventilation/perfusion (V'/Q') ratios, the rate of washout of N2 and exogenous tracer gas was almost indistinguishable. At low V'/Q', the N2 washout lagged the tracer gas washout. At very low V'/Q', N2 became trapped in the acinus. Under low V'/Q' conditions, breathing pure O2 introduced a marked asymmetry between the inspiratory and expiratory gas flow rates that was not present when breathing air. DISCUSSION: The use of pure O2 to washout N2 increases O2 uptake in low V'/Q' units. This generates a background gas flow into the acinus that opposes flow out of the acinus during expiration, and so delays the washout of N2.

Development of in-airway laser absorption spectroscopy for respiratory based measurements of cardiac output.

Respiratory approaches to determining cardiac output in humans are securely rooted in mass balance and therefore potentially highly accurate. To address existing limitations in the gas analysis, we developed an in-airway analyser based on laser absorption spectroscopy to provide analyses every 10 ms. The technique for estimating cardiac output requires both a relatively soluble and insoluble tracer gas, and we employed acetylene and methane for these, respectively. A multipass cell was used to provide sufficient measurement sensitivity to enable analysis directly within the main gas stream, thus avoiding errors introduced by sidestream gas analysis. To assess performance, measurements of cardiac output were made during both rest and exercise on five successive days in each of six volunteers. The measurements were extremely repeatable (coefficient of variation ~ 7%). This new measurement technology provides a stable foundation against which the algorithm to calculate cardiac output can be further developed.

Continuous-Wave Cavity-Enhanced Polarimetry for Optical Rotation Measurement of Chiral Molecules.

Precise optical rotation measurements play an important role in the analysis of chiral molecules in various fields, especially in biological chemistry and pharmacology. In this paper, we demonstrate a new variant of continuous-wave cavity-enhanced polarimetry for detecting the optical activity of two enantiomers of a chiral molecule at 730 nm. It is based on a signal-reversing technique for which the chiral specific rotation is directly determined by the cavity ring-down signal from two counter-propagating beams in a bow-tie cavity. In particular, we ensure reproducible excitation of both modes by broadening the linewidth of a diode laser source by application of a radio frequency perturbation to its injection current. The performance of the polarimeter is demonstrated for the specific rotation of (+)- and (-)-α-pinene in different environments, including the pure vapor, open air, and the liquid phase; the detection precision ranges between 10-5 and 10-4 degrees per cavity pass depending on the environment. The apparatus is a robust and practical tool for quantifying chirality and can be developed for the entire visible and near-infrared spectral regions.

A dynamic model of the body gas stores for carbon dioxide, oxygen, and inert gases that incorporates circulatory transport delays to and from the lung.

Many models of the body's gas stores have been generated for specific purposes. Here, we seek to produce a more general purpose model that: 1) is relevant for both respiratory (CO2 and O2) and inert gases; 2) is based firmly on anatomy and not arbitrary compartments; 3) can be scaled to individuals; and 4) incorporates arterial and venous circulatory delays as well as tissue volumes so that it can reflect rapid transients with greater precision. First, a "standard man" of 11 compartments was produced, based on data compiled by the International Radiation Protection Commission. Each compartment was supplied via its own parallel circulation, the arterial and venous volumes of which were based on reported tissue blood volumes together with data from a detailed anatomical model for the large arteries and veins. A previously published model was used for the blood gas chemistry of CO2 and O2. It was not permissible ethically to insert pulmonary artery catheters into healthy volunteers for model validation. Therefore, validation was undertaken by comparing model predictions with previously published data and by comparing model predictions with experimental data for transients in gas exchange at the mouth following changes in alveolar gas composition. Overall, model transients were fastest for O2, intermediate for CO2, and slowest for N2. There was good agreement between model estimates and experimentally measured data. Potential applications of the model include estimation of closed-loop gain for the ventilatory chemoreflexes and improving the precision associated with multibreath washout testing and respiratory measurement of cardiac output.NEW & NOTEWORTHY A model for the body gas stores has been generated that is applicable to both respiratory gases (CO2 and O2) and inert gases. It is based on anatomical details for organ volumes and blood contents together with anatomical details of the large arteries. It can be scaled to the body size and composition of different individuals. The model enables mixed venous gas compositions to be predicted from the systemic arterial compositions.

The correlation between breath acetone and blood betahydroxybutyrate in individuals with type 1 diabetes.

Ketone testing is an important element of the self-management of illness in type 1 diabetes. The aim of the present study was to see if a breath test for acetone could be used to predict quantitatively the levels of the ketone betahydroxybutyrate in the blood of those with type 1 diabetes, and thus be used as an alternative to capillary testing for ketones. Simultaneous capillary ketones and breath acetone were measured in 72 individuals with type 1 diabetes attending a diabetes clinic and on 9 individuals admitted to hospital with diabetic ketoacidosis. Capillary blood measurements ranged from 0.1 mmol l-1 (the lower limit of the ketone monitor) to over 7 mmol l-1, with breath acetone varying between 0.25 and 474 parts per million by volume. The two variables were found to be correlated and allowed modelling to be carried out which separated breath acetone levels into three categories corresponding to normal, elevated and 'at risk' levels of blood ketones. The results on this limited set of participants suggest that a breath acetone test could be a simple, non-invasive substitute for capillary ketone measurement in type 1 diabetes.

Accurate real-time FENO expirograms using complementary optical sensors.

The fraction of exhaled nitric oxide (FENO) is an important biomarker for the diagnosis and management of asthma and other pulmonary diseases associated with airway inflammation. In this study we report on a novel method for accurate, highly time-resolved, real time detection of FENO at the mouth. The experimental arrangement is based on a combination of optical sensors for the determination of the temporal profile of exhaled NO and CO2 concentrations. Breath CO2 and exhalation flow are measured at the mouth using diode laser absorption spectroscopy (at 2 µm) and differential pressure sensing, respectively. NO is determined in a sidestream configuration using a quantum cascade laser based, cavity-enhanced absorption cell (at 5.2 µm) which simultaneously measures sidestream CO2. The at-mouth and sidestream CO2 measurements are used to enable the deconvolution of the sidestream NO measurement back to the at-mouth location. All measurements have a time resolution of 0.1 s, limited by the requirement of a reasonable limit of detection for the NO measurement, which on this timescale is 4.7 ppb (2 σ). Using this methodology, NO expirograms (FENOgrams) were measured and compared for eight healthy volunteers. The FENOgrams appear to differ qualitatively between individuals and the hope is that the dynamic information encoded in these FENOgrams will provide valuable additional insight into the location of the inflammation in the airways and potentially predict a response to therapy. A validation of the measurements at low-time resolution is provided by checking that results from previous studies that used a two-compartment model of NO production can be reproduced using our technology.

Tuberculosis from transmission in clinics in high HIV settings may be far higher than contact data suggest.

BACKGROUND: In South Africa, it is generally estimated that only 0.5-0.6% of people's contacts occur in clinics. Both people with infectious tuberculosis and people with increased susceptibility to disease progression may spend more time in clinics, however, increasing the importance of clinic-based transmission to overall disease incidence.METHODS: We developed an illustrative mathematical model of Mycobacterium tuberculosis transmission in clinics and other settings. We assumed that 1% of contact time occurs in clinics. We varied the ratio of clinic contact time of human immunodeficiency virus (HIV) positive people compared to HIV-negative people, and of people with infectious TB compared to people without TB, while keeping the overall proportion of contact time occurring in clinics, and each person's total contact time, constant.RESULTS: With clinic contact rates respectively 10 and 5 times higher in HIV-positive people and people with TB, 10.7% (plausible range 8.5-13.4%) of TB resulted from transmission in clinics. With contact rates in HIV-positive people and people with TB respectively 5 and 2 times higher, 5.3% (plausible range 4.3-6.3%) of all TB was due to transmission in clinics.CONCLUSION: The small amount of contact time that generally occurs in clinics may greatly underestimate their contribution to TB disease in high TB-HIV burden settings.

Novel measure of lung function for assessing disease activity in asthma.

INTRODUCTION: In asthma, lung function measures are often discordant with clinical features such as disease activity or control. METHODS: We investigated a novel technique that provides a measure (σCL) of unevenness (inhomogeneity) in lung inflation/deflation. In particular, we compared σCL with FEV1% predicted (FEV1%pred) as measures of disease activity in the asthmatic lung. RESULTS: σCL correlated modestly with FEV1%pred. However, σCL is not simply a proxy for FEV1%pred as the effects of salbutamol on the two parameters were unrelated. Importantly, σCL reflected disease control better than FEV1. DISCUSSION: We conclude that σCL shows promise as an objective measure of disease activity in asthma.