Validation of a new spectrometer for noninvasive measurement of cardiac output

Acetylene is a blood-soluble gas and for many years its uptake rate during rebreathing tests has been used to calculate the flow rate of blood through the lungs (normally equal to cardiac output) as well as the volume of lung tissue. A new, portable, noninvasive instrument for cardiac output determination using the acetylene uptake method is described. The analyzer relies on nondispersive IR absorption spectroscopy as its principle of operation and is configured for extractive (side-stream) sampling. The instrument affords exceptionally fast (30 ms, 10%–90%, 90%–10%, at 500 mL min–1 flow rates), interference-free, simultaneous measurement of acetylene, sulfur hexafluoride (an insoluble reference gas used in the cardiac output calculation), and carbon dioxide (to determine alveolar ventilation), with good (typically ±2% full-scale) signal-to-noise ratios. Comparison tests with a mass spectrometer using serially diluted calibration gas samples gave excellent (R2>0.99) correlation for all three gases, validating the IR system's linearity and accuracy. A similar level of agreement between the devices also was observed during human subject C2H2 uptake tests (at rest and under incremental levels of exercise), with the instruments sampling a common extracted gas stream. Cardiac output measurements by both instruments were statistically equivalent from rest to 90% of maximal oxygen consumption; the physiological validity of the measurements was confirmed by the expected linear relationship between cardiac output and oxygen consumption, with both the slope and intercept in the published range. These results indicate that the portable, low-cost, rugged prototype analyzer discussed here is suitable for measuring cardiac output noninvasively in a point-of-care setting

Artificial photosynthesis: semiconductor photocatalytic fixation of CO_2 to afford higher organic compounds

Carbon dioxide is an appealing renewable feedstock for industrial chemical processes. This does not mean, however, that all chemical processes using CO_2 are environmentally-friendly. Perspectives on the sustainability of CO_2 utilization and artificial photosynthesis are provided. The discussions focus on the photocatalytic production of C_x (x ≥ 2) compounds, where all the carbon in the products is derived from CO_2. This area of research, while promising, has received far less attention than analogous systems leading to C_1 products

Prediction of skin penetration using machine learning methods

Improving predictions of the skin permeability coefficient is a difficult problem. It is also an important issue with the increasing use of skin patches as a means of drug delivery. In this work, we applyK-nearest-neighbour regression, single layer networks, mixture of experts and Gaussian processes to predict the permeability coefficient. We obtain a considerable improvement over the quantitative structureactivity relationship (QSARs) predictors. We show that using five features, which are molecular weight, solubility parameter, lipophilicity, the number of hydrogen bonding acceptor and donor groups, can produce better predictions than the one using only lipophilicity and the molecular weight. The Gaussian process regression with five compound features gives the best performance in this work

The application of stochastic machine learning methods in the prediction of skin penetration

Original article can be found at: http://www.sciencedirect.com Copyright ElsevierImproving predictions of skin permeability is a significant problem for which mathematical solutions have been sought for around twenty years. However, the current approaches are limited by the nature of the models chosen and the nature of the dataset. This is an important problem, particularly with the increased use of transdermal and topical drug delivery systems. In this work, we apply K-nearest-neighbour regression, single layer networks, mixture of experts and Gaussian processes to predict the skin permeability coefficient of penetrants. A considerable improvement, both statistically and in terms of the accuracy of predictions, over the current quantitative structure-permeability relationships (QSPRs) was found. Gaussian processes provided the most accurate predictions, when compared to experimentally generated results. It was also shown that using five molecular descriptors - molecular weight, solubility parameter, lipophilicity, the number of hydrogen bonding acceptor and donor groups - can produce better predictions than when using only lipophilicity and the molecular weight, which is an approach commonly found with QSPRs. The Gaussian process regression with five compound features was shown to give the best performance in this work. Therefore, Gaussian processes would appear to provide a viable alternative to the development of predictive models for skin absorption and underpin more realistically mechanistic understandings of the physical process of the percutaneous absorption of exogenous chemicals. (C) 2010 Elsevier B.V. All rights reserved.Peer reviewe

Measuring kinetic coefficients by molecular dynamics simulation of zone melting

Molecular dynamics simulations are performed to measure the kinetic coefficient at the solid-liquid interface in pure gold. Results are obtained for the (111), (100) and (110) orientations. Both Au(100) and Au(110) are in reasonable agreement with the law proposed for collision-limited growth. For Au(111), stacking fault domains form, as first reported by Burke, Broughton and Gilmer [J. Chem. Phys. {\bf 89}, 1030 (1988)]. The consequence on the kinetics of this interface is dramatic: the measured kinetic coefficient is three times smaller than that predicted by collision-limited growth. Finally, crystallization and melting are found to be always asymmetrical but here again the effect is much more pronounced for the (111) orientation.Comment: 8 pages, 9 figures (for fig. 8 : [email protected]). Accepted for publication in Phys. Rev.

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Bacteria-Specific Neutrophil Dysfunction Associated with Interferon-Stimulated Gene Expression in the Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a poorly understood condition with greater than 30% mortality. Massive recruitment of neutrophils to the lung occurs in the initial stages of the ARDS. Significant variability in the severity and duration of ARDS-associated pulmonary inflammation could be linked to heterogeneity in the inflammatory capacity of neutrophils. Interferon-stimulated genes (ISGs) are a broad gene family induced by Type I interferons. While ISGs are central to anti-viral immunity, the potential exists for these genes to evoke extensive modification in cellular response in other clinical settings. In this prospective study, we sought to determine if ISG expression in circulating neutrophils from ARDS patients is associated with changes in neutrophil function. Circulating neutrophil RNA was isolated, and hierarchical clustering ranked patients' expression of three ISGs. Neutrophil response to pathogenic bacteria was compared between normal and high ISG-expressing neutrophils. High neutrophil ISG expression was found in 25 of 95 (26%) of ARDS patients and was associated with reduced migration toward interleukin-8, and altered responses to Staphylococcus aureus, but not Pseudomonas aeruginosa, which included decreased p38 MAP kinase phosphorylation, superoxide anion release, interleukin-8 release, and a shift from necrotic to apoptotic cell death. These alterations in response were reflected in a decreased capacity to kill S. aureus, but not P. aeruginosa. Therefore, the ISG expression signature is associated with an altered circulating neutrophil response phenotype in ARDS that may predispose a large subgroup of patients to increased risk of specific bacterial infections

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<p><b>Pod-IVR Pharmacokinetics in macaques</b> (A) <i>In vivo</i> release of TDF and FTC from each pod-IVR (N = 6/time point) over the course of the efficacy study determined by residual drug measurements from the pod-IVRs that were in place for 19 weeks with IVRs exchanged for new devices every 2 weeks. The top and bottom of the boxes show the 75th and 25th percentiles, respectively, and the line in the middle of the box is the median value. The dotted lines show the mean (N = 6) <i>in vivo</i> release from identical pod-IVRs obtained during the PK study preceding this efficacy study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157061#pone.0157061.ref026" target="_blank">26</a>]. (B) <i>In vivo</i> release profile for individual macaques (T1-T6) shows variability between animals. (C) TDF, TFV, TDF+TFV, and FTC levels in vaginal fluids collected at each ring exchange. Vaginal fluids were collected with Weck-Cel sponges proximal and distal to the pod-IVR placement. The dotted horizontal lines correspond to the medians from our previous PK study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157061#pone.0157061.ref026" target="_blank">26</a>]. Left panels-proximal; Right panels-distal; Dots-median.</p