Characterization of a high-resolution breath acetone meter for ketosis monitoring

Background: The ketone bodies beta-hydroxybutyrate (BHB) and acetone are endogenous products of fatty acid metabolism. Although ketone levels can be monitored by measuring either blood BHB or breath acetone, determining the precise correlation between these two measurement methods has been challenging. The purpose of this study is to characterize the performance of a novel portable breath acetone meter (PBAM) developed by Readout, Inc., to compare single versus multiple daily ketone measurements, and to compare breath acetone (BrAce) and blood BHB measurements. Methods: We conducted a 14-day prospective observational cohort study of 21 subjects attempting to follow either a low-carbohydrate/ketogenic or a standard diet. Subjects were asked to concurrently measure both blood BHB and BrAce five times per day and report the results using an online data entry system. We evaluated the utility of multiple daily measurements by calculating the coefficient of variation (CV) for each daily group of measurements. We calculated the correlation between coincident BrAce and blood BHB measurements using linear ordinary least squares regression analysis. We assessed the ability of the BrAce measurement to accurately predict blood BHB states using receiver operating characteristic (ROC) analysis. Finally, we calculated a daily ketone exposure (DKE) using the area under the curve (AUC) of a ketone concentration versus time graph and compared the DKE of BrAce and blood BHB using linear ordinary least squares regression. Results: BrAce and blood BHB varied throughout the day by an average of 44% and 46%, respectively. The BrAce measurement accurately predicted whether blood BHB was greater than or less than the following thresholds: 0.3 mM (AUC = 0.898), 0.5 mM (AUC = 0.854), 1.0 mM (AUC = 0.887), and 1.5 mM (AUC = 0.935). Coincident BrAce and blood BHB measurements were moderately correlated with Conclusions: The results validated the performance of the PBAM. The BrAce/BHB correlation was similar to literature values where BrAce was measured using highly accurate lab instruments. Additionally, BrAce measurements using the PBAM can be used to predict blood BHB states. The relatively high daily variability of ketone levels indicate that single blood or breath ketone measurements are often not sufficient to assess daily ketone exposure for most users. Finally, although single coincident blood and breath ketone measurements show only a moderate correlation, possibly due to the temporal lag between BrAce and blood BHB, daily ketone exposures for blood and breath are highly correlated

Tipificación en Gutierrezia (Asteraceae, Astereae)

During the course of the revision of the South American species of Gutierrezia, we have detected names that require typification. After the analysis of the protologues and the herbarium specimens, we designated eight lectotypes and one neotype for nine names of the Gutierrezia genus and we assigned the category of holotype to one specimen. A detailed discussion is provided for each case.Durante el transcurso de la revisión de las especies sudamericanas de Gutierrezia, hemos podido hallar nombres que requieren tipificación. Luego del análisis de los protologos y especímenes de herbario, hemos designado ocho lectótipos y un neótipo para nueve nombres del género Gutierrezia. Además, se asignó la categoría de hólotipo a un especimen. Se provee una discusión detallada para cada nombre

Externally excited traveling pulses in a neon glow discharge.

http://www.archive.org/details/externallyexcite00rattU.S. Navy (U.S.N.) author

Combining polynomial chaos expansions and genetic algorithm for the coupling of electrophysiological models

The number of computational models in cardiac research has grown over the last decades. Every year new models with di erent assumptions appear in the literature dealing with di erences in interspecies cardiac properties. Generally, these new models update the physiological knowledge using new equations which reect better the molecular basis of process. New equations require the fi tting of parameters to previously known experimental data or even, in some cases, simulated data. This work studies and proposes a new method of parameter adjustment based on Polynomial Chaos and Genetic Algorithm to nd the best values for the parameters upon changes in the formulation of ionic channels. It minimizes the search space and the computational cost combining it with a Sensitivity Analysis. We use the analysis of di ferent models of L-type calcium channels to see that by reducing the number of parameters, the quality of the Genetic Algorithm dramatically improves. In addition, we test whether the use of the Polynomial Chaos Expansions improves the process of the Genetic Algorithm search. We conclude that it reduces the Genetic Algorithm execution in an order of 103 times in the case studied here, maintaining the quality of the results. We conclude that polynomial chaos expansions can improve and reduce the cost of parameter adjustment in the development of new models.Peer ReviewedPostprint (author's final draft

Acute stress impairs sensorimotor gating via the neurosteroid allopregnanolone in the prefrontal cortex

Ample evidence indicates that environmental stress impairs information processing, yet the underlying mechanisms remain partially elusive. We showed that, in several rodent models of psychopathology, the neurosteroid allopregnanolone (AP) reduces the prepulse inhibition (PPI) of the startle, a well-validated index of sensorimotor gating. Since this GABAA receptor activator is synthesized in response to acute stress, we hypothesized its participation in stress-induced PPI deficits. Systemic AP administration reduced PPI in C57BL/6J mice and Long-Evans, but not Sprague-Dawley rats. These effects were reversed by isoallopregnanolone (isoAP), an endogenous AP antagonist, and the GABAA receptor antagonist bicuculline and mimicked by AP infusions in the medial prefrontal cortex (mPFC). Building on these findings, we tested AP's implication in the PPI deficits produced by several complementary regimens of acute and short-term stress (footshock, restraint, predator exposure, and sleep deprivation). PPI was reduced by acute footshock, sleep deprivation as well as the combination of restraint and predator exposure in a time- and intensity-dependent fashion. Acute stress increased AP concentrations in the mPFC, and its detrimental effects on PPI were countered by systemic and intra-mPFC administration of isoAP. These results collectively indicate that acute stress impairs PPI by increasing AP content in the mPFC. The confirmation of these mechanisms across distinct animal models and several acute stressors strongly supports the translational value of these findings and warrants future research on the role of AP in information processing

Fiscal policy, banks and the financial crisis

This paper studies the effectiveness of Euro Area (EA) fiscal policy, during the recent financial crisis, using an estimated New Keynesian model with a bank. A key dimension of policy in the crisis was massive government support for banks-that dimension has so far received little attention in the macro literature. We use the estimated model to analyze the effects of bank asset losses, of government support for banks, and other fiscal stimulus measures, in the EA. Our results suggest that support for banks had a stabilizing effect on EA output, consumption and investment. Increased government purchases helped to stabilize output, but crowded out consumption. Higher transfers to households had a positive impact on private consumption, but a negligible effect on output and investment. Banking shocks and increased government spending explain half of the rise in the public debt/GDP ratio since the onset of the crisis

Localized functionalization of single nanopores

We demonstrate the localization of chemical functionality at the entrance of single nanopores for the first time by using the controlled growth of an oxide ring. Nanopores were fabricated by Focused Ion Beam machining on silicon platforms, locally derivatized by ion beam assisted oxide deposition, and further functionalized with DNA probes via silane chemistry. Ionic current recorded through single nanopores at various stages of the fabrication process demonstrated that the apertures can be locally functionalized with DNA probes. Future applications for this functional platform include the selective detection of biological organisms and molecules by ionic current blockade measurements

La gran erupción de hace 4.2 ka cal en Cerro Blanco, Zona Volcánica Central, Andes: nuevos datos sobre los depósitos eruptivos holocenos en la Puna sur y regiones adyacentes

The eruption of the Cerro Blanco Volcanic Complex, in the southern Puna, NW Argentina dated at 4410–4150 a cal BP, was investigated to produce new information on stratigraphy, geomorphology, physical volcanology, radiocarbon dating, petrography, and geochemistry. Identification of pre–, syn–, and post–caldera products allowed us to estimate the distribution of the Plinian fallout during the paroxysmal syn–caldera phase of the eruption. The new results provide evidence for a major rhyolitic explosive eruption that spread volcanic deposits over an area of ~500,000 km2, accumulating > 100 km3 of tephra (bulk volume). This last value exceeds the lower threshold of Volcanic Explosive Index (VEI) of 7. Ash-fall deposits mantled the region at distances > 400 km from source and thick pyroclastic-flow deposits filled neighbouring valleys up to 35 km away. This eruption is the largest documented during the past five millennia in the Central Volcanic Zone of the Andes, and is probably one of the largest Holocene explosive eruptions in the world. We have also identified two additional rhyolitic eruptions in the region from two other eruptive sources: one during the Early–Holocene and another in the Late–Holocene. The identification and characterisation of these significant volcanic events provide new constraints into regional Holocene geological and archaeological records, and offer extensive regional chronostratigraphic markers over a wide geographical area of South America.La erupción del Complejo Volcánico Cerro Blanco en el sur de la Puna, noroeste de Argentina (4410–4150 a BP) se investigó para obtener nueva información sobre estratigrafía, geomorfología, volcanología física, dataciones por radiocarbono, petrografía y geoquímica. La caracterización de los productos en relación a la evolución de la caldera de Cerro Blanco permitió estimar la distribución de los depósitos de ceniza de la fase paroxísmica Plineana de la erupción. Estos novedosos resultados evidencian una gran erupción explosiva riolítica que generó depósitos cineríticos en un área de aproximadamente 500.000 km2, acumulando > 100 km3 de tefra (volumen total). Este último valor supera el umbral inferior del Índice de Explosividad Volcánica (IEV) de 7. Los depósitos de caída de ceniza cubrieron la región, llegando a más de 400 km desde el Complejo Volcánico de Cerro Blanco, y los potentes depósitos de flujos piroclásticos rellenaron los valles vecinos alcanzando una distancia de 35 km. Esta erupción es la más grande documentada durante los últimos cinco milenios en la Zona Volcánica Central de los Andes y es probablemente una de las mayores erupciones explosivas holocenas del mundo. Además, se han identificado otras dos erupciones riolíticas en la región procedentes de otros dos centros eruptivos: una durante el Holoceno temprano y otra en el Holoceno tardío. La identificación y caracterización de estos grandes eventos volcánicos proporcionan nuevas guías para los registros geológicos y arqueológicos regionales del Holoceno, siendo marcadores cronostratigráficos de aplicación a una extensa área geográfica de América del Sur

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine