Assessment of gas exchange in lung disease: balancing accuracy against feasibility

While the principles underlying alveolar gas exchange have been well-known for over 50 years, we still struggle to assess gas exchange in hypoxemic patients. Unfortunately, simple measurements lack discrimination while complex measurements are infeasible in clinical care. The paper by Karbing et al. in this issue seeks a middle ground based on the arterial PO2 (PaO2)/inspired O2 fraction (FIO2) ratio measured at different FIO2s with the outcomes fed into proprietary software to account for both shunting and ventilation/perfusion inequality. Whether this is the optimal compromise between measurement difficulty and information available will have to be answered by those willing to test the approach in their own patients

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

Acute hypoxia reduces plasma myostatin independent of hypoxic dose

Background: Muscle atrophy is seen ~ 25 % of patients with cardiopulmonary disorders, such as chronic obstructive pulmonary disorder and chronic heart failure. Multiple hypotheses exist for this loss, including inactivity, inflammation, malnutrition and hypoxia. Healthy individuals exposed to chronic hypobaric hypoxia also show wasting, suggesting hypoxia alone is sufficient to induce atrophy. Myostatin regulates muscle mass and may underlie hypoxic-induced atrophy. Our previous work suggests a decrease in plasma myostatin and increase in muscle myostatin following 10 hours of exposure to 12 % O2. Aims: To establish the effect of hypoxic dose on plasma myostatin concentration. Concentration of plasma myostatin following two doses of normobaric hypoxia (10.7 % and 12.3 % O2) in a randomised, single-blinded crossover design (n = 8 lowlanders, n = 1 Sherpa), with plasma collected pre (0 hours), post (2 hours) and 2 hours following (4 hours) exposure. Results: An effect of time was noted, plasma myostatin decreased at 4 hours but not 2 hours relative to 0 hours (p = 0.01; 0 hours = 3.26 [0.408] ng.mL-1, 2 hours = 3.33, [0.426] ng.mL-1, 4 hours = 2.92, [0.342] ng.mL-1). No difference in plasma myostatin response was seen between hypoxic conditions (10.7 % vs. 12.3 % O2). Myostatin reduction in the Sherpa case study was similar to the lowlander cohort. Conclusions: Decreased myostatin peptide expression suggests hypoxia in isolation is sufficient to challenge muscle homeostasis, independent of confounding factors seen in chronic cardiopulmonary disorders, in a manner consistent with our previous work. Decreased myostatin peptide may represent flux towards peripheral muscle, or a reduction to protect muscle mass. Chronic adaption to hypoxia does not appear to protect against this response, however larger cohorts are needed to confirm this. Future work will examine tissue changes in parallel with systemic effects

Chromophore-bearing NH_2-terminal domains of phytochromes A and B determine their photosensory specificity and differential light lability

In early seedling development, far-red-light-induced deetiolation is mediated primarily by phytochrome A (phyA), whereas red-light-induced deetiolation is mediated primarily by phytochrome B (phyB). To map the molecular determinants responsible for this photosensory specificity, we tested the activities of two reciprocal phyA/phyB chimeras in diagnostic light regimes using overexpression in transgenic Arabidopsis. Although previous data have shown that the NH_2-terminal halves of phyA and phyB each separately lack normal activity, fusion of the NH_2-terminal half of phyA to the COOH-terminal half of phyB (phyAB) and the reciprocal fusion (phyBA) resulted in biologically active phytochromes. The behavior of these two chimeras in red and far-red light indicates: (i) that the NH2-terminal halves of phyA and phyB determine their respective photosensory specificities; (ii) that the COOH-terminal halves of the two photoreceptors are necessary for regulatory activity but are reciprocally inter-changeable and thus carry functionally equivalent determinants; and (iii) that the NH_2-terminal halves of phyA and phyB carry determinants that direct the differential light lability of the two molecules. The present findings suggest that the contrasting photosensory information gathered by phyA and phyB through their NH_2-terminal halves may be transduced to downstream signaling components through a common biochemical mechanism involving the regulatory activity of the COOH-terminal domains of the photoreceptors

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics

Two-lane traffic rules for cellular automata: A systematic approach

Microscopic modeling of multi-lane traffic is usually done by applying heuristic lane changing rules, and often with unsatisfying results. Recently, a cellular automaton model for two-lane traffic was able to overcome some of these problems and to produce a correct density inversion at densities somewhat below the maximum flow density. In this paper, we summarize different approaches to lane changing and their results, and propose a general scheme, according to which realistic lane changing rules can be developed. We test this scheme by applying it to several different lane changing rules, which, in spite of their differences, generate similar and realistic results. We thus conclude that, for producing realistic results, the logical structure of the lane changing rules, as proposed here, is at least as important as the microscopic details of the rules

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Experimental growth law for bubbles in a "wet" 3D liquid foam

We used X-ray tomography to characterize the geometry of all bubbles in a liquid foam of average liquid fraction $\phi_l\approx 17$ and to follow their evolution, measuring the normalized growth rate $\mathcal{G}=V^{-{1/3}}\frac{dV} {dt}$ for 7000 bubbles. While $\mathcal{G}$ does not depend only on the number of faces of a bubble, its average over $f-$faced bubbles scales as $G_f\sim f-f_0$ for large $f$s at all times. We discuss the dispersion of $\mathcal{G}$ and the influence of $V$ on $\mathcal{G}$.Comment: 10 pages, submitted to PR

Towards a Macroscopic Modelling of the Complexity in Traffic Flow

We present a macroscopic traffic flow model that extends existing fluid-like models by an additional term containing the second derivative of the safe velocity. Two qualitatively different shapes of the safe velocity are explored: a conventional Fermi-type function and a function exhibiting a plateau at intermediate densities. The suggested model shows an extremely rich dynamical behaviour and shows many features found in real-world traffic data.Comment: submitted to Phys. Rev.