Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function.

UNLABELLED Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.

Physiological plasticity to water flow habitat in the damselfish, Acanthochromis polyacanthus: linking phenotype to performance

The relationships among animal form, function and performance are complex, and vary across environments. Therefore, it can be difficult to identify morphological and/or physiological traits responsible for enhancing performance in a given habitat. In fishes, differences in swimming performance across water flow gradients are related to morphological variation among and within species. However, physiological traits related to performance have been less well studied. We experimentally reared juvenile damselfish, Acanthochromis polyacanthus, under different water flow regimes to test 1) whether aspects of swimming physiology and morphology show plastic responses to water flow, 2) whether trait divergence correlates with swimming performance and 3) whether flow environment relates to performance differences observed in wild fish. We found that maximum metabolic rate, aerobic scope and blood haematocrit were higher in wave-reared fish compared to fish reared in low water flow. However, pectoral fin shape, which tends to correlate with sustained swimming performance, did not differ between rearing treatments or collection sites. Maximum metabolic rate was the best overall predictor of individual swimming performance; fin shape and fish total length were 3.3 and 3.7 times less likely than maximum metabolic rate to explain differences in critical swimming speed. Performance differences induced in fish reared in different flow environments were less pronounced than in wild fish but similar in direction. Our results suggest that exposure to water motion induces plastic physiological changes which enhance swimming performance in A. polyacanthus. Thus, functional relationships between fish morphology and performance across flow habitats should also consider differences in physiology.

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

BACKGROUND White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

Revisiting the ISN Flow Parameters, using a variable IBEX pointing strategy

The Interstellar Boundary Explorer (IBEX) has observed the interstellar neutral (ISN) gas flow over the past 6 yr during winter/spring when the Earth's motion opposes the ISN flow. Since IBEX observes the interstellar atom trajectories near their perihelion, we can use an analytical model based upon orbital mechanics to determine the interstellar parameters. Interstellar flow latitude, velocity, and temperature are coupled to the flow longitude and are restricted by the IBEX observations to a narrow tube in this parameter space. In our original analysis we found that pointing the spacecraft spin axis slightly out of the ecliptic plane significantly influences the ISN flow vector determination. Introducing the spacecraft spin axis tilt into the analytical model has shown that IBEX observations with various spin axis tilt orientations can substantially reduce the range of acceptable solutions to the ISN flow parameters as a function of flow longitude. The IBEX operations team pointed the IBEX spin axis almost exactly within the ecliptic plane during the 2012-2014 seasons, and about 5° below the ecliptic for half of the 2014 season. In its current implementation the analytical model describes the ISN flow most precisely for the spin axis orientation exactly in the ecliptic. This analysis refines the derived ISN flow parameters with a possible reconciliation between velocity vectors found with IBEX and Ulysses, resulting in a flow longitude lambda∞ = 74.°5 ± 1.°7 and latitude beta∞ = -5.°2 ± 0.°3, but at a substantially higher ISN temperature than previously reported.

Temporal variations of dyspnea, fatigue, and lung function in chronic lung disease

Background. Research investigating symptom management in patients with chronic obstructive pulmonary disease (COPD) largely has been undertaken assuming the homeostatic construct, without regard to potential roles of circadian rhythms. Temporal relations among dyspnea, fatigue, peak expiratory flow rate (PEFR) and objective measures of activity/rest have not been reported in COPD. ^ Objectives. The specific aims of this study were to (1) explore the 24-hour patterns of dyspnea, fatigue, and PEFR in subjects with COPD; (2) examine the relations among dyspnea, fatigue, and PEFR in COPD; and (3) examine the relations among objective measures of activity/rest and dyspnea, fatigue, and PEFR in COPD. ^ Methods. The repeated-measures design involved 10 subjects with COPD who self-assessed dyspnea and fatigue by 100 mm visual analog scales, and PEFR by peak flow meter in their home 5 times a day for 8 days. Activity/rest was measured by wrist actigraphy. Single and population mean cosinor analyses and correlations were computed for dyspnea, fatigue, and PEFR; correlations were done among these variables and activity/rest. ^ Results. Circadian rhythms were documented by single cosinor analysis in 40% of the subjects for dyspnea, 60% for fatigue, and 60% for PEFR. The population cosinor analysis of PEFR yielded a significant rhythm (p < .05). The 8-day 24-hour means of dyspnea and fatigue was moderately correlated (r = .48, p < .01). Dyspnea and PEFR, and fatigue and PEFR, were weakly correlated in a negative way (r = −.11, p < .05 and r = −.15, p < .01 respectively). Weak to moderate correlations (r = .12–.34, p < .05) were demonstrated between PEFR and mean activity level measured up to 4 hours before PEFR measurement. ^ Conclusions. The findings suggest that (1) the dyspnea and fatigue experienced by COPD patients are moderately related, (2) there is a weak to modest positive relation between PEFR and activity levels, and (3) temporal variation in lung function may not affect the dyspnea and fatigue experienced by patients with COPD. Further research, examining the relations among dyspnea, fatigue, PEFR, and activity/rest is needed. Replication of this study is suggested with a larger sample size. ^

Organization and function of platelet glycoprotein Ib-IX complex

Glycoprotein (GP) Ib-IX complex, the second most abundant receptor expressed on the platelet surface, plays critical roles in haemostasis and thrombosis by binding to its ligand, von Willebrand factor (vWF). Defect or malfunction of the complex leads to severe bleeding disorders, heart attack or stroke. Comprised of three type I transmembrane subunits—GPIbα, GPIbβ and GPIX, efficient expression of the GPIb-IX complex requires all three subunits, as evident from genetic mutations identified in the patients and reproduced in transfected Chinese hamster ovary (CHO) cells. However, how the subunits are assembled together and how the complex function is regulated is not fully clear. By probing the interactions among the three subunits in transfected cells, we have demonstrated that the transmembrane domains of the three subunits interact with one another, facilitating formation of the two membrane-proximal disulfide bonds between GPIbα and GPIbβ. We have also identified the interface between extracellular domains of GPIbβ and GPIX, and provided evidence suggesting a direct interaction between extracellular domains of GPIbα and GPIX. All of these interactions are not only critical for correct assembly and consequently efficient expression of the GPIb-IX complex on the cell surface, but also for its function, such as the proper ligand binding, since removing the two inter-subunit disulfide bonds significantly hampers vWF binding to the complex under both static and physiological flow conditions. The two inter-subunit disulfide bonds are also critical for regulating the ectodomain shedding of GPIbα by the GPIbβ cytoplasmic domain. Mutations in the juxtamembrane region of the GPIbβ cytoplasmic domain deregulate GPIbα shedding, and such deregulation is further enhanced when the two inter-subunit disulfide bonds are removed. In summary, we have established the overall organization of the GPIb-IX complex, and the importance of proper organization on its function. ^

(Table 1) Characteristics of South Pole personnel according to forced expiratory flow (FEF25-75) response to altitude

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF25-75) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF25-75 increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF25-75 (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF25-75. Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF25-75. Greater levels of endothelin-1 in individuals with decreased FEF25-75 suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of beta2-adrenergic receptors.

Debris flow magnitudes: a global catalog

The episodic occurrence of debris flow events in response to stochastic precipitation and wildfire events makes hazard prediction challenging. Previous work has shown that frequency-magnitude distributions of non-fire-related debris flows follow a power law, but less is known about the distribution of post-fire debris flows. As a first step in parameterizing hazard models, we use frequency-magnitude distributions and cumulative distribution functions to compare volumes of post-fire debris flows to non-fire-related debris flows. Due to the large number of events required to parameterize frequency-magnitude distributions, and the relatively small number of post-fire event magnitudes recorded in the literature, we collected data on 73 recent post-fire events in the field. The resulting catalog of 988 debris flow events is presented as an appendix to this article. We found that the empirical cumulative distribution function of post-fire debris flow volumes is composed of smaller events than that of non-fire-related debris flows. In addition, the slope of the frequency-magnitude distribution of post-fire debris flows is steeper than that of non-fire-related debris flows, evidence that differences in the post-fire environment tend to produce a higher proportion of small events. We propose two possible explanations: 1) post-fire events occur on shorter return intervals than debris flows in similar basins that do not experience fire, causing their distribution to shift toward smaller events due to limitations in sediment supply, or 2) fire causes changes in resisting and driving forces on a package of sediment, such that a smaller perturbation of the system is required in order for a debris flow to occur, resulting in smaller event volumes.

Linear instability of orthogonal compressible leading-edge boundary layer flow

Instability analysis of compressible orthogonal swept leading-edge boundary layer flow was performed in the context of BiGlobal linear theory. 1, 2 An algorithm was developed exploiting the sparsity characteristics of the matrix discretizing the PDE-based eigenvalue problem. This allowed use of the MUMPS sparse linear algebra package 3 to obtain a direct solution of the linear systems associated with the Arnoldi iteration. The developed algorithm was then applied to efficiently analyze the effect of compressibility on the stability of the swept leading-edge boundary layer and obtain neutral curves of this flow as a function of the Mach number in the range 0 ≤ Ma ≤ 1. The present numerical results fully confirmed the asymptotic theory results of Theofilis et al. 4 Up to the maximum Mach number value studied, it was found that an increase of this parameter reduces the critical Reynolds number and the range of the unstable spanwise wavenumbers.

Flow and fracture behaviour of high performance alloys

Based on our needs, that is to say, through precise simulation of the impact phenomena that may occur inside a jet engine turbine with an explicit non-linear finite element code, four new material models are postulated. Each one of is calibrated for four high-performance alloys that can be encountered in a modern jet engine. A new uncoupled material model for high strain and ballistic is proposed. Based on a Johnson-Cook type model, the proposed formulation introduces the effect of the third deviatoric invariant by means of three different Lode angle dependent functions. The Lode dependent functions are added to both plasticity and failure models. The postulated model is calibrated for a 6061-T651 aluminium alloy with data taken from the literature. The fracture pattern predictability of the JCX material model is shown performing numerical simulations of various quasi-static and dynamic tests. As an extension of the above-mentioned model, a modification in the thermal softening behaviour due to phase transformation temperatures is developed (JCXt). Additionally, a Lode angle dependent flow stress is defined. Analysing the phase diagram and high temperature tests performed, phase transformation temperatures of the FV535 stainless steel are determined. The postulated material model constants for the FV535 stainless steel are calibrated. A coupled elastoplastic-damage material model for high strain and ballistic applications is presented (JCXd). A Lode angle dependent function is added to the equivalent plastic strain to failure definition of the Johnson-Cook failure criterion. The weakening in the elastic law and in the Johnson-Cook type constitutive relation implicitly introduces the Lode angle dependency in the elastoplastic behaviour. The material model is calibrated for precipitation hardened Inconel 718 nickel-base superalloy. The combination of a Lode angle dependent failure criterion with weakened constitutive equations is proven to predict fracture patterns of the mechanical tests performed and provide reliable results. A transversely isotropic material model for directionally solidified alloys is presented. The proposed yield function is based a single linear transformation of the stress tensor. The linear operator weighs the degree of anisotropy of the yield function. The elastic behaviour, as well as the hardening, are considered isotropic. To model the hardening, a Johnson-Cook type relation is adopted. A material vector is included in the model implementation. The failure is modelled with the Cockroft-Latham failure criterion. The material vector allows orienting the reference orientation in any other that the user may need. The model is calibrated for the MAR-M 247 directionally solidified nickel-base superalloy.

Realistic performance prediction in nanostructured solar cells as a function of nanostructure dimensionality and density

The behavior of quantum dot, quantum wire, and quantum well InAs/GaAs solar cells is studied with a very simplified model based on experimental results in order to assess their performance as a function of the low bandgap material volume fraction fLOW. The efficiency of structured devices is found to exceed the efficiency of a non-structured GaAs cell, in particular under concentration, when fLOW is high; this condition is easier to achieve with quantum wells. If three different quasi Fermi levels appear with quantum dots the efficiency can be much higher.

Performance of pressure control valves and flow meters precision in operational irrigation-water balance accuracy

In pressure irrigation-water distribution networks, pressure regulating devices for controlling the discharged flow rate by irrigation units are needed due to the variability of flow rate. In addition, applied water volume is used controlled operating the valve during a calculated time interval, and assuming constant flow rate. In general, a pressure regulating valve PRV is the commonly used pressure regulating device in a hydrant, which, also, executes the open and close function. A hydrant feeds several irrigation units, requiring a wide range in flow rate. In addition, some flow meters are also available, one as a component of the hydrant and the rest are placed downstream. Every land owner has one flow meter for each group of field plots downstream the hydrant. Its lecture could be used for refining the water balance but its accuracy must be taken into account. Ideal PRV performance would maintain a constant downstream pressure. However, the true performance depends on both upstream pressure and the discharged flow rate. The objective of this work is to asses the influence of the performance on the applied volume during the whole irrigation events in a year. The results of the study have been obtained introducing the flow rate into a PRV model. Variations on flow rate are simulated by taking into account the consequences of variations on climate conditions and also decisions in irrigation operation, such us duration and frequency application. The model comprises continuity, dynamic and energy equations of the components of the PRV.

Choked flow in water/CO2 solutions on air-independent propulsion systems

We develop a simplified model of choked flow in pipes for CO2-water solutions as an important step in the modelling of a whole hydraulic system with the intention of eliminating the carbon dioxide generated in air-independent submarine propulsion. The model is based on an approximate fitting of the homogeneous isentropic solution upstream of a valve (or any other area restriction), for given fluid conditions at the entrance. The relative maximum choking back-pressure is computed as a function of area restriction ratio. Although the procedure is generic for gas solutions, numeric values for the non-dimensional parameters in the analysis are developed only for choking in the case of carbon dioxide solutions up to the pure-water limit.

Cálculo de la recarga natural en grandes áreas, en función de la litología y la precipitación = Calculation of natural recharge in large areas, as a function of lithology and rainfall

En una región amplia como España se demuestra —mediante inferencias estadísticas sobre una muestra completa de 875 manantiales en los que se conoce su caudal medio y la litología de su área de alimentación y que han sido agrupados en regiones de distinta pluviometría— que la recarga media anual es una fracción fija de la precipitación media para cada litología. Se han establecido así unas tasas de recarga respecto de la precipitación para seis grupos litológicos de diferente permeabilidad: arenas, gravas y formaciones aluviales en general, 8.3%; conglomerados, 5.6%; areniscas, 7.3%; calizas y dolomías, 34.3%; margas, margocalizas, limos y arcillas, 3.3%; otras rocas, 1.3%. Teniendo en cuenta la representatividad de España, la cual tiene una gran variabilidad de litología, pluviometría, topografía, etcétera, estas tasas de recarga respecto de la precipita-ción son probablemente valores cuasi universales que pueden ser utilizados para estimar la recarga media o los recursos hídricos subterráneos medios de regiones amplias en cualquier parte del mundo, salvo en regiones especiales, como las que tienen permafrost, por ejemplo. En todo caso, estas tasas de recarga podrían ser retocadas para cada región según sus particulares características. Los datos de precipitación y litología son muy corrientes, por lo que el método puede ser ampliamente utilizado para completar balances hidráulicos.In a region as large as Spain, annual mean recharge is shown to be a fixed proportion of the mean rainfall for each lithology. This determination is based on statistical inferences from a complete sample of 875 springs for which mean flow and catchment areas are known and which have been grouped into distinct rainfall regions. Recharge rates have thus been established with respect to rainfall for six lithological groups with different permeability: sands, gravels and generally alluvial formations, 8.3%; conglomerates, 5.6%; sandstones, 7.3%; limestone and dolomite 34.3%; marls, marly limestones, silts and clays, 3.3%; and hard rocks, 1.3%. Considering the representativeness of Spain, which is large in size and has a highly varied lithology, topography and rainfall, these recharge rates for rainfall are probably quasi-universal values that can be used to estimate average recharge or average groundwater resources of large regions in any part of the world (except in special cases such as areas with permafrost, for example). For any case, these recharge rates can be adapted to each region according to its particular characteristics. Rainfall and lithology data are very common, and so the method can be widely used to calculate hydraulic balances.