A unified solution to the small scale problems of the Lambda CDM model II: introducing parent-satellite interaction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Deformation and tidal evolution of close-in planets and satellites using a Maxwell viscoelastic rheology

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension

We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI. Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24 h, animals were randomized into subgroups without or with intraabdominal hypertension (15 mmHg) and ventilated with positive end expiratory pressure = 5 cmH(2)O and tidal volume of 6 or 10 ml/kg during 1 h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1 beta, IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed. With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1 beta, IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume. Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.

Improvement in ARDS experimental model installation: Low mortality rate and maintenance of hemodynamic stability

Introduction: Many experimental models using lung lavage have been developed for the study of acute respiratory distress syndrome (ARDS). The original technique has been modified by many authors, resulting in difficulties with reproducibility. There is insufficient detail on the lung injury models used, including hemodynamic stability during animal preparation and drawbacks encountered such as mortality. The authors studied the effects of the pulmonary recruitment and the use of fixed tidal volume (Vt) or fixed inspiratory pressure in the experimental ARDS model installation. Methods: Adult rabbits were submitted to repeated lung lavages with 30 ml/kg warm saline until the ARDS definition (PaO2/FiO(2) <= 100) was reached. The animals were divided into three groups, according to the technique used for mechanical ventilation: 1) fixed Vt of 10 ml/kg; 2) fixed inspiratory pressure (IP) with a tidal volume of 10 ml/kg prior to the first lung lavage; and 3) fixed Vt of 10 ml/kg with pulmonary recruitment before the first lavage. Results: The use of alveolar recruitment maneuvers, and the use of a fixed Vt or IP between the lung lavages did not change the number of lung lavages necessary to obtain the experimental model of ARDS or the hemodynamic stability of the animals during the procedure. A trend was observed toward an increased mortality rate with the recruitment maneuver and with the use of a fixed IP. Discussion: There were no differences between the three study groups, with no disadvantage in method of lung recruitment, either fixed tidal volume or fixed inspiratory pressure, regarding the number of lung lavages necessary to obtain the ARDS animal model. Furthermore, the three different procedures resulted in good hemodynamic stability of the animals, and low mortality rate. (C) 2012 Elsevier Inc. All rights reserved.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome A Meta-analysis

Context Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS. Objective To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS. Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012. Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations. Data Extraction Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I-2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I-2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I-2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I-2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I-2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I-2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I-2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results. Conclusions Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation. JAMA. 2012;308(16):1651-1659 www.jama.com

Vibrating Membrane Devices Deliver Aerosols More Efficient than Standard Devices: A Study in a Neonatal Upper Airway Model

Abstract Background: Aerosol therapy in preterm infants is challenging, as a very small proportion of the drug deposits in the lungs. Aim: Our aim was to compare efficiency of standard devices with newer, more efficient aerosol delivery devices. Methods: Using salbutamol as a drug marker, we studied two prototypes of the investigational eFlow(®) nebulizer for babies (PARI Pharma GmbH), a jet nebulizer (Intersurgical(®) Cirrus(®)), and a pressurized metered dose inhaler (pMDI; GSK) with a detergent-coated holding chamber (AeroChamber(®) MV) in the premature infant nose throat-model (PrINT-model) of a 32-week preterm infant (1,750 g). A filter or an impactor was placed below the infant model's "trachea" to capture the drug dose or particle size, respectively, that would have been deposited in the lung. Results: Lung dose (percentage of nominal dose) was 1.5%, 6.8%, and 18.0-20.6% for the jet nebulizer, pMDI-holding chamber, and investigational eFlow nebulizers, respectively (p<0.001). Jet nebulizer residue was 69.4% and 10.7-13.9% for the investigational eFlow nebulizers (p<0.001). Adding an elbow extension between the eFlow and the model significantly lowered lung dose (p<0.001). A breathing pattern with lower tidal volume decreased deposition in the PrINT-model and device residue (p<0.05), but did not decrease lung dose. Conclusions: In a model for infant aerosol inhalation, we confirmed low lung dose using jet nebulizers and pMDI-holding chambers, whereas newer, more specialized vibrating membrane devices, designed specifically for use in preterm infants, deliver up to 20 times more drug to the infant's lung.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

A Model Study of the Circulation in the Pearl River Estuary (PRE) and Its Adjacent Coastal Waters: 1. Simulations and Comparison with Observations

The Princeton Ocean Model is used to study the circulation features in the Pearl River Estuary and their responses to tide, river discharge, wind, and heat flux in the winter dry and summer wet seasons. The model has an orthogonal curvilinear grid in the horizontal plane with variable spacing from 0.5 km in the estuary to 1 km on the shelf and 15 sigma levels in the vertical direction. The initial conditions and the subtidal open boundary forcing are obtained from an associated larger-scale model of the northern South China Sea. Buoyancy forcing uses the climatological monthly heat fluxes and river discharges, and both the climatological monthly wind and the realistic wind are used in the sensitivity experiments. The tidal forcing is represented by sinusoidal functions with the observed amplitudes and phases. In this paper, the simulated tide is first examined. The simulated seasonal distributions of the salinity, as well as the temporal variations of the salinity and velocity over a tidal cycle are described and then compared with the in situ survey data from July 1999 and January 2000. The model successfully reproduces the main hydrodynamic processes, such as the stratification, mixing, frontal dynamics, summer upwelling, two-layer gravitational circulation, etc., and the distributions of hydrodynamic parameters in the Pearl River Estuary and coastal waters for both the winter and the summer season.

RESPIRATORY COMPENSATION MECHANISMS IN THE UPPER AND LOWER RESPIRATORY TRACTS OF AN ANIMAL MODEL AFTER SUBCHRONIC INHALATION EXPOSURE TO FORMALDEHYDE: IMPLICATIONS FOR TOXICOLOGY RISK ASSESSMENT (DEPOSITION, DOSE RECEIVED, RESPONSE)

The potential for significant human populations to experience long-term inhalation of formaldehyde and reports of symptomatology due to this exposure has led to a considerable interest in the toxicologic assessment of risk from subchronic formaldehyde exposures using animal models. Since formaldehyde inhalation depresses certain respiratory parameters in addition to its other forms of toxicity, there is a potential for the alteration of the actual dose received by the exposed individual (and the resulting toxicity) due to this respiratory effect. The respiratory responses to formaldehyde inhalation and the subsequent pattern of deposition were therefore investigated in animals that had received subchronic exposure to the compound, and the potential for changes in the formaldehyde dose received due to long-term inhalation evaluated. Male Sprague-Dawley rats were exposed to either 0, 0.5, 3, or 15 ppm formaldehyde for 6 hours/day, 5 days/week for up to 6 months. The patterns of respiratory response, deposition and the compensation mechanisms involved were then determined in a series of formaldehyde test challenges to both the upper and to the lower respiratory tracts in separate groups of subchronically exposed animals and age-specific controls (four concentration groups, two time points). In both the control and pre-exposed animals, there was a characteristic recovery of respiratory parameters initially depressed by formaldehyde inhalation to at or approaching pre-exposure levels within 10 minutes of the initiation of exposure. Also, formaldehyde deposition was found to remain very high in the upper and lower tracts after long-term exposure. Therefore, there was probably little subsequent effect on the dose received by the exposed individual that was attributable to the repeated exposures. There was a diminished initial minute volume response in test challenges of both the upper and lower tracts of animals that had received at least 16 weeks of exposure to 15 ppm, with compensatory increases in tidal volume in the upper tract and respiratory rate in the lower tract. However, this dose-related effect was probably not relevant to human risk estimation because this formaldehyde dose is in excess of that experienced by human populations. ^

EOT11a - Global Empirical Ocean Tide model from multi-mission satellite altimetry, with links to model results

EOT11a is a global (E)mpirical (O)cean (T)ide model derived in 2011 by residual analysis of multi-mission satellite (a)ltimeter data. EOT11a includes amplitudes and phases of the main astronomical tides M2, S2, N2, K2, 2N2, O1, K1, P2, and Q1, the non-linear constituent M4, the long period tides Mm and Mf, and the radiational tide S1. Ocean tides as well as loading tides are provided. EOT11a was computed by means of residual tidal analysis of multi-mission altimeter data from TOPEX/Poseidon, ERS-2, ENVISAT, and Jason-1/2, as far as acquired between September 1992 and April 2010. The resolution of 7.5'x7.5' is identical with FES2004 which was used as reference model for the residual tide analysis. The development of EOT11a was funded by the Deutsche Forschungsgemeinschaft (DFG) under grant BO1228/6-2.

Flow separation and roughness lengths over large bedforms in a tidal environment

This study characterises the shape of the flow separation zone (FSZ) and wake region over large asymmetric bedforms under tidal flow conditions. High resolution bathymetry, flow velocity and turbulence data were measured along two parallel transects in a tidal channel covered with bedforms. The field data are used to verify the applicability of a numerical model for a systematic study using the Delft3D modelling system and test the model sensitivity to roughness length. Three experiments are then conducted to investigate how the FSZ size and wake extent vary depending on tidally-varying flow conditions, water levels and bathymetry. During the ebb, a large FSZ occurs over the steep lee side of each bedform. During the flood, no flow separation develops over the bedforms having a flat crest; however, a small FSZ is observed over the steepest part of the crest of some bedforms, where the slope is locally up to 15°. Over a given bedform morphology and constant water levels, no FSZ occurs for velocity magnitudes smaller than 0.1 m s**-1; as the flow accelerates, the FSZ reaches a stable size for velocity magnitudes greater than 0.4 m s**-1. The shape of the FSZ is not influenced by changes in water levels. On the other hand, variations in bed morphology, as recorded from the high-resolution bathymetry collected during the tidal cycle, influence the size and position of the FSZ: a FSZ develops only when the maximum lee side slope over a horizontal distance of 5 m is greater than 10°. The height and length of the wake region are related to the length of the FSZ. The total roughness along the transect lines is an order of magnitude larger during the ebb than during the flood due to flow direction in relation to bedform asymmetry: during the ebb, roughness is created by the large bedforms because a FSZ and wake develops over the steep lee side. The results add to the understanding of hydrodynamics of natural bedforms in a tidal environment and may be used to better parameterise small-scale processes in large-scale studies.

Observations on the propagation of internal tidal waves on the continental slope off Sierra Leone

During R/V Meteor-cruise no. 30 4 moorings with 17 current meters were placed on the continental slope of Sierra Leone at depths between 81 and 1058 meters. The observation period started on March 8, 1973, 16.55 hours GMT and lasted 19 days for moorings M30_068MOOR, M30_069MOOR, M30_070MOOR on the slope and 9 days for M30_067MOOR on the shelf. One current meter recorded at location M30_067MOOR for 22 days. Hydrographic data were collected at 32 stations by means of the "Kieler Multi-Meeressonde". Harmonic analysis is applied to the first 15 days of the time series to determine the M2 and S2 tides. By vertically averaging of the Fourier coefficients the field of motion is separated into its barotropic and its baroclinic component. The expected error generated by white Gaussian noise is estimated. To estimate the influence of the particular vertical distribution of the current meters, the barotropic M2 tide is calculated by ommitting and interchanging time series of different moorings. It is shown that only the data of moorings M30_069MOOR, M30_070MOOR and M30_067MOOR can be used. The results for the barotropic M2 tide agree well with the previous publications of other authors. On the slope at a depth of 1000 m there is a free barotropic wave under the influence of the Coriolis-force propagating along the slope with an amplitude of 3.4 cm S**-1. On the shelf, the maximum current is substantially greater (5.8 cm s**-1) and the direction of propagation is perpendicular to the slope. As for the continental slope a separation into different baroclinic modes using vertical eigenmodes is not reasonable, an interpretation of the total baroclinic wave field is tried by means of the method of characteristis. Assuming the continental slope to generate several linear waves, which superpose, baroclinic tidal ellipses are calculated. The scattering of the direction of the major axes M30_069MOOR is in contrast to M30_070MOOR, where they are bundled within an angle of 60°. This is presumably caused by the different character of the bottom topography in the vicinity of the two moorings. A detailed discussion of M30_069MOOR is renounced since the accuracy of the bathymetric chart is not sufficient to prove any relation between waves and topography. The bundeling of the major axes at M30_070MOOR can be explained by the longslope changes of the slope, which cause an energy transfer from the longslope barotropic component to the downslope baroclinic component. The maximum amplitude is found at a depth of 245 m where it is expected from the characteristics originating at the shelf edge. Because of the dominating barotropic tide high coherence is found between most of the current meters. To show the influence of the baroclinic tidal waves, the effect of the mean current is considered. There are two periods nearly opposite longshore mean current. For 128 hours during each of these periods, starting on March 11, 05.00, and March 21, 08.30, the coherences and energy spectra are calculated. The changes in the slope of the characteristics are found in agreement with the changes of energy and coherence. Because of the short periods of nearly constant mean current, some of the calculated differences of energy and coherence are not statistically significant. For the M2 tide a calculation of the ratios of vertically integrated total baroclinic energy and vertically integrated barotropic kinetic energy is carried out. Taking into account both components (along and perpendicular to the slope) the obtained values are 0.75 and 0.98 at the slope and 0.38 at the shelf. If each component is considered separately, the ratios are 0.39 and 1.16 parallel to the slope and 5.1 and 15.85 for the component perpendicular to it. Taking the energy transfer from the longslope component to the doenslope component into account, a simple model yields an energy-ratio of 2.6. Considering the limited application of the theory to the real conditions, the obtained are in agreement with the values calculated by Sandstroem.

A comprehensive analysis of tidal notches in the Mediterranean Sea

Recent works (Evelpidou et al., 2012) suggest that the modern tidal notch is disappearing worldwide due sea level rise over the last century. In order to assess this hypothesis, we measured modern tidal notches in several of sites along the Mediterranean coasts. We report observations on tidal notches cut along carbonate coasts from 73 sites from Italy, France, Croatia, Montenegro, Greece, Malta and Spain, plus additional observations carried outside the Mediterranean. At each site, we measured notch width and depth, and we described the characteristics of the biological rim at the base of the notch. We correlated these parameters with wave energy, tide gauge datasets and rock lithology. Our results suggest that, considering 'the development of tidal notches the consequence of midlittoral bioerosion' (as done in Evelpidou et al., 2012) is a simplification that can lead to misleading results, such as stating that notches are disappearing. Important roles in notch formation can be also played by wave action, rate of karst dissolution, salt weathering and wetting and drying cycles. Of course notch formation can be augmented and favoured also by bioerosion which can, in particular cases, be the main process of notch formation and development. Our dataset shows that notches are carved by an ensemble rather than by a single process, both today and in the past, and that it is difficult, if not impossible, to disentangle them and establish which one is prevailing. We therefore show that tidal notches are still forming, challenging the hypothesis that sea level rise has drowned them.