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A continuous source for the generation of pure HONO mixtures was developed and characterized, which is based on the Henry's law solubility of HONO in acidic aqueous solutions. With the help of a peristaltic pump, diluted nitrite and sulfuric acid solutions are mixed in a temperature-controlled stripping coil, which is operated with pure nitrogen or synthetic air at gas flow rates of 0.5–2 L min−1. Caused by the acidic conditions of the aqueous phase (pH ≈ 2.5), nitrite is almost completely converted into HONO, which partitions to the gas phase limited by its known solubility in water. The source shows a fast time response of ∼ 2 min (0 %–90 %) at higher concentrations and an excellent long-term stability (2σ noise < 1 %). The HONO emission of the source perfectly correlates with the nitrite concentration from the sub-ppb range up to 500 ppb. The rate of NOx formation increases quadratically with the HONO concentration from non-detectable values at atmospheric relevant HONO concentrations reaching a NOx content of 1.6 % at 500 ppb. A general equation based on Henry's law is developed, whereby the HONO concentration of the source can be calculated using measured experimental parameters, i.e. nitrite concentration, liquid flow rates, gas flow rate, pH of the solution, and temperature of the stripping coil. In the equation, the known Henry's law constant of HONO in sulfuric acid solutions is used. For the calculation of the effective Henry's law constant, the acid dissociation equilibrium of HONO / nitrite is used as a variable to adjust the theoretical HONO concentration to the measured values. From the average of all experimental data the equilibrium of HONO / nitrite is described well by pKa=1021.53/T-0.449. The pKa of 3.0 ± 0.1 (1σ) at 25 ∘C is in good agreement with the range of 2.8–3.28 published in former studies. A standard deviation between all measured and theoretical HONO concentrations of only ±3.8 % was observed, and a conservative upper-limit accuracy of the HONO concentration of better 10 % is estimated. Thus, for the first time, a stable HONO source is developed which can be used for the absolute calibration of HONO instruments.

The last 2 decades have seen substantial technological advances in the development of low-cost air pollution instruments using small sensors. While their use continues to spread across the field of atmospheric chemistry, the air quality monitoring community, and for commercial and private use, challenges remain in ensuring data quality and comparability of calibration methods. This study introduces a seven-step methodology for the field calibration of low-cost sensor systems using reference instrumentation with user-friendly guidelines, open-access code, and a discussion of common barriers to such an approach. The methodology has been developed and is applicable for gas-phase pollutants, such as for the measurement of nitrogen dioxide (NO2) or ozone (O3). A full example of the application of this methodology to a case study in an urban environment using both multiple linear regression (MLR) and the random forest (RF) machine-learning technique is presented with relevant R code provided, including error estimation. In this case, we have applied it to the calibration of metal oxide gas-phase sensors (MOSs). Results reiterate previous findings that MLR and RF are similarly accurate, though with differing limitations. The methodology presented here goes a step further than most studies by including explicit transparent steps for addressing model selection, validation, and tuning, as well as addressing the common issues of autocorrelation and multicollinearity. We also highlight the need for standardized reporting of methods for data cleaning and flagging, model selection and tuning, and model metrics. In the absence of a standardized methodology for the calibration of low-cost sensor systems, we suggest a number of best practices for future studies using low-cost sensor systems to ensure greater comparability of research.

Abstract Background Non-invasive delivery of nebulized surfactant has been a neonatology long-pursued goal. Nevertheless, the clinical efficacy of nebulized surfactant remains inconclusive, in part, due to the great technical challenges of depositing nebulized drugs in the lungs of preterm infants. The aim of this study was to investigate the feasibility of delivering nebulized surfactant (poractant alfa) in vitro and in vivo with an adapted, neonate-tailored aerosol delivery strategy. Methods Particle size distribution of undiluted poractant alfa aerosols generated by a customized eFlow-Neos nebulizer system was determined by laser diffraction. The theoretical nebulized surfactant lung dose was estimated in vitro in a clinical setting replica including a neonatal continuous positive airway pressure (CPAP) circuit, a cast of the upper airways of a preterm neonate, and a breath simulator programmed with the tidal breathing pattern of an infant with mild respiratory distress syndrome (RDS). A dose-response study with nebulized surfactant covering the 100–600 mg/kg nominal dose-range was conducted in RDS-modelling, lung-lavaged spontaneously-breathing rabbits managed with nasal CPAP. The effects of nebulized poractant alfa on arterial gas exchange and lung mechanics were assessed. Exogenous alveolar disaturated-phosphatidylcholine (DSPC) in the lungs was measured as a proxy of surfactant deposition efficacy. Results Laser diffraction studies demonstrated suitable aerosol characteristics for inhalation (mass median diameter, MMD = 3 μm). The mean surfactant lung dose determined in vitro was 13.7% ± 4.0 of the 200 mg/kg nominal dose. Nebulized surfactant delivered to spontaneously-breathing rabbits during nasal CPAP significantly improved arterial oxygenation compared to animals receiving CPAP only. Particularly, the groups of animals treated with 200 mg/kg and 400 mg/kg of nebulized poractant alfa achieved an equivalent pulmonary response in terms of oxygenation and lung mechanics as the group of animals treated with instilled surfactant (200 mg/kg). Conclusions The customized eFlow-Neos vibrating-membrane nebulizer system efficiently generated respirable aerosols of undiluted poractant alfa. Nebulized surfactant delivered at doses of 200 mg/kg and 400 mg/kg elicited a pulmonary response equivalent to that observed after treatment with an intratracheal surfactant bolus of 200 mg/kg. This bench-characterized nebulized surfactant delivery strategy is now under evaluation in Phase II clinical trial (EUDRACT No.:2016–004547-36).

Reliable measurements of atmospheric trace gases are necessary for both, a better understanding of the chemical processes occurring in the atmosphere, and for the validation of model predictions. Nitrogen dioxide (NO2) is a toxic gas and is thus a regulated air pollutant. Besides, it is of major importance for the oxidation capacity of the atmosphere and plays a pivotal role in the formation of ozone and acid precipitation. Detection of NO2 is a difficult task since many of the different commercial techniques used are affected by interferences. The chemiluminescence instruments that are used for indirect NO2 detection in monitoring networks and smog chambers use either molybdenum or photolytic converters and are affected by either positive (NOy) or negative interferences (radical formation in the photolytic converter). Erroneous conclusions on NO2 can be drawn if these interferences are not taken into consideration. In the present study, NO2 measurements in the urban atmosphere, in a road traffic tunnel and in a smog-chamber using different commercial techniques, i.e. chemiluminescence instruments with molybdenum or photolytic converters, a Luminol based instrument and a new NO2-LOPAP, were compared with spectroscopic techniques, i.e. DOAS and FTIR. Interferences of the different instruments observed during atmospheric measurements were partly characterised in more detail in the smog chamber experiments. Whereas all the commercial instruments showed strong interferences, excellent agreement was obtained between a new NO2-LOPAP instrument and the FTIR technique for the measurements performed in the smog chamber.

A compact and simple instrument for the sensitive detection of NO2 in the atmosphere has been developed. NO2 is sampled in a stripping coil by a selective chemical reaction, converted into a highly absorbing dye, which is detected by long path absorption in a liquid core waveguide. Several interferences were quantified in the laboratory which so far can all be neglected. The significant interferences against HONO and O3 were suppressed by using an upstream HONO/O3-scrubber. The instrument has a detection limit of 2 pptv, an accuracy of 10 % and a precision of 0.5 % for 3 min time resolution. Thus, the new NO2-LOPAP technique is more sensitive than known commercial NO2 instruments. The new analyzer is much simpler to apply than other highly sensitive and selective NO2 methods, e.g. LIF or REMPI methods. The new instrument allows an absolute calibration that can be easily performed with liquid nitrite standards, which is a significant advantage compared with other NO2 measurement techniques for which NO2 calibration gas mixtures are typically necessary. The new instrument has been validated against the chemiluminescence technique during an urban field campaign and against the FTIR technique in a smog chamber under complex photosmog conditions. The data sets exhibit high correlation and excellent agreement.

NO2 concentrations were measured by various instruments during the NO3Comp campaign at the atmosphere simulation chamber SAPHIR at Forschungszentrum Jülich, Germany, in June 2007. Analytical methods included photolytic conversion with chemiluminescence (PC-CLD), broadband cavity ring-down spectroscopy (BBCRDS), pulsed cavity ring-down spectroscopy (CRDS), incoherent broadband cavity-enhanced absorption spectroscopy (IBB\-CEAS), and laser-induced fluorescence (LIF). All broadband absorption spectrometers were optimized for the detection of the main target species of the campaign, NO3, but were also capable of detecting NO2 simultaneously with reduced sensitivity. NO2 mixing ratios in the chamber were within a range characteristic of polluted, urban conditions, with a maximum mixing ratio of approximately 75 ppbv. The overall agreement between measurements of all instruments was excellent. Linear fits of the combined data sets resulted in slopes that differ from unity only within the stated uncertainty of each instrument. Possible interferences from species such as water vapor and ozone were negligible under the experimental conditions.

The oxidation capacity of the highly polluted urban area of Santiago, Chile has been evaluated during a summer measurement campaign carried out from 8–20 March 2005. The hydroxyl (OH) radical budget was evaluated employing a simple quasi-photostationary-state model (PSS) constrained with simultaneous measurements of HONO, HCHO, O3, NO, NO2, j(O1D), j(NO2), 13 alkenes and meteorological parameters. In addition, a zero dimensional photochemical box model based on the Master Chemical Mechanism (MCMv3.1) has been used to estimate production rates and total free radical budgets, including OH, HO2 and RO2. Besides the above parameters, the MCM model has been constrained by the measured CO and volatile organic compounds (VOCs) including alkanes and aromatics. Both models simulate the same OH concentration during daytime indicating that the primary OH sources and sinks included in the simple PSS model predominate. Mixing ratios of the main OH radical precursors were found to be in the range 0.8–7 ppbv (HONO), 0.9–11 ppbv (HCHO) and 0–125 ppbv (O3). The alkenes average mixing ratio was ~58 ppbC accounting for ~12% of the total identified non-methane hydrocarbons (NMHCs). During the daytime (08:00 h–19:00 h), HONO photolysis was shown to be the most important primary OH radical source comprising alone ~55% of the total initial production rate, followed by alkene ozonolysis (~24%) and photolysis of HCHO (~16%) and O3 (~5%). The calculated average and maximum daytime OH production rates from HONO photolysis was 1.7 ppbv h−1 and 3.1 ppbv h−1, respectively. Based on the experimental results a strong photochemical daytime source of HONO is proposed. A detailed analysis of the sources of OH radical precursors has also been carried out.

Background and Aim. The efficiency of tele-monitoring or tele-assistance in patients with severe chronic ventilatory failure in home mechanical ventilation (HMV) is still being investigated. Our aim was to test the feasibility of a model which consisted in: 1) once a week nocturnal telemonitoring, supervised by a doctor in charge in a Respiratory Intensive Care Unit, who also provided a telephone-counselling (24/7) on demand; 2) a scheduled visit every two months. Methods. A 2-year observational study was carried out on 16 patients ventilated for at least 1 year and for ≥ 8 hours /day. Once a week patients underwent a nocturnal monitoring during HMV. The compliance was evaluated by regular transmission of data and regular follow-up, the level of satisfaction by a telephonequestionnaire. Results. The adherence to the protocol study was good in 9/16 (56%) and poor in 7/16 (44%) patients. For each patient, the mean number of connections was 46,12 ± 36.39 (70.7% of that expected), in those with good compliance it increased to 63.8 ± 32.7 (114% of that expected). The median hours of connection was 343 (138- 1019) and 89 (0-521) for patients with good and poor compliance respectively, p=0.038. The mean scheduled visits for patient with good compliance was 6.9 ± 4.14 (100% of that expected). Emergency visits were avoided in 62.5% of cases. The satisfaction score was higher in compliant versus non compliant patients (p=0.019). Conclusion. This pilot study showed that the telemonitoring system employed was feasible and effective in more compliant patients who claimed a high rate of satisfaction.

In this paper we focus on the human arm motion capture, which is motivated by the requirements in physical rehabilitation and training of stroke patients in the same way as monitoring of elderly person activities. The proposed methodology uses a data fusion of low-cost and low-weight MEMS sensors jointly to an a priori knowledge of the arm anatomy. The main goal is to estimate the arm position, the anatomical movements of the shoulder and its accelerations. We propose a discrete optimization based-approach which aims to search the optimal attitude ambiguity directly without decorrelation of ambiguity, and to computing the baseline vector consequently. The originality of this paper is to apply the discrete optimization to track the desired trajectory of a nonlinear system such as the Human Movement in the presence of uncertainties. The global asymptotic convergence of the nonlinear observer is guaranteed. Extensive tests of the presented methodology with real world data illustrate the effectiveness of the proposed procedure.

Identification of elastic fibers at the ultrastructural level is accomplished by a post-embedding immunohistochemical technique using the protein A-colloidal gold method. Antisera against elastins from human dermis and rat aorta have been characterized by radioimmunoassay and then applied to thin sections of rat blood vessels. Two fixative solutions and two embedding media have been tested. Both antibodies bind to elastic fibers of normal arteries and veins, indicating crossreactions among organs and species. The high sensitivity of this method is demonstrated by its application to the detection of neo-elastogenesis in the intimal thickening of aortic grafts.

Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodeling of articular cartilage in response to abnormal mechanical stresses is postulated.

Antibodies to native types I, II, IX, and XI collagen were measured, using a 125I-solid-phase radioimmunoassay, in serum from 104 patients with rheumatic diseases (rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis). In all disease groups, antibodies to type II collagen occurred with greater frequency than antibodies to type I collagen (11-35% versus 5-23%). Antibodies to type XI collagen were the most frequent: They were present in approximately 50% of the patients in the rheumatoid arthritis, Paget's disease, and osteoporosis groups. Antibodies to type IX collagen were found at a high frequency in the rheumatoid arthritis group only (44%). Analysis of the clinical data suggested that the presence of antibodies to collagen was associated with disease that was less severe or of shorter duration.