Improved coronary artery definition with T2-weighted, free-breathing, three-dimensional coronary MRA.

BACKGROUND: Three-dimensional (3D) navigator-gated and prospectively corrected free-breathing coronary magnetic resonance angiography (MRA) allows for submillimeter image resolution but suffers from poor contrast between coronary blood and myocardium. Data collected over >100 ms/heart beat are also susceptible to bulk cardiac and respiratory motion. To address these problems, we examined the effect of a T2 preparation prepulse (T2prep) for myocardial suppression and a shortened acquisition window on coronary definition. METHODS AND RESULTS: Eight healthy adult subjects and 5 patients with confirmed coronary artery disease (CAD) underwent free-breathing 3D MRA with and without T2prep and with 120- and 60-ms data-acquisition windows. The T2prep resulted in a 123% (P<0. 001) increase in contrast-to-noise ratio (CNR). Coronary edge definition was improved by 33% (P<0.001). Acquisition window shortening from 120 to 60 ms resulted in better vessel definition (11%; P<0.001). Among patients with CAD, there was a good correspondence with disease. CONCLUSIONS: Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.

Programació d'una aplicació gràfica per l'anàlisi de senyals usant LDB (Local Discriminant Bases) i MLDB (Modified LDB)

Tot seguit presentem un entorn per analitzar senyals de tot tipus amb LDB (Local Discriminant Bases) i MLDB (Modified Local Discriminant Bases). Aquest entorn utilitza funcions desenvolupades en el marc d’una tesi en fase de desenvolupament. Per entendre part d’aquestes funcions es requereix un nivell de coneixement avançat de processament de senyals. S’han extret dels treballs realitzats per Naoki Saito [3], que s’han agafat com a punt de partida per la realització de l’algorisme de la tesi doctoral no finalitzada de Jose Antonio Soria. Aquesta interfície desenvolupada accepta la incorporació de nous paquets i funcions. Hem deixat un menú preparat per integrar Sinus IV packet transform i Cosine IV packet transform, tot i que també podem incorporar-n’hi altres. L’aplicació consta de dues interfícies, un Assistent i una interfície principal. També hem creat una finestra per importar i exportar les variables desitjades a diferents entorns. Per fer aquesta aplicació s’han programat tots els elements de les finestres, en lloc d’utilitzar el GUIDE (Graphical User Interface Development Enviroment) de MATLAB, per tal que sigui compatible entre les diferents versions d’aquest programa. En total hem fet 73 funcions en la interfície principal (d’aquestes, 10 pertanyen a la finestra d’importar i exportar) i 23 en la de l’Assistent. En aquest treball només explicarem 6 funcions i les 3 de creació d’aquestes interfícies per no fer-lo excessivament extens. Les funcions que explicarem són les més importants, ja sigui perquè s’utilitzen sovint, perquè, segons la complexitat McCabe, són les més complicades o perquè són necessàries pel processament del senyal. Passem cada entrada de dades per part de l’usuari per funcions que ens detectaran errors en aquesta entrada, com eliminació de zeros o de caràcters que no siguin números, com comprovar que són enters o que estan dins dels límits màxims i mínims que li pertoquen.

Génériques des médicaments antiépileptiques [Generics of antiepileptic drugs]

Generic substitution of antiepileptic drugs (EAD) have limited use because epilepsy is a chronic disease, seizure recurrence has an important impact of the quality of life and the potential risk of accidents. EADs have a narrow therapeutic window, non negligible side effects and complex interactions. Bioavailability of generic EADs, tested in healthy men during a limited period of time must be within the 90% IC, in which means that serum levels can range from 80% to 125% of the original drug. A slight drop in serum level could increase the risk of seizure recurrence, as indicated by several publications. Although no formal studies regarding cost effectiveness and the rate of seizure recurrence is available yet, the prevailing consensus recommends not to replace an original antiepileptic drug by a generic, due to the harmful risk of seizure recurrence.

Estudi edàfic dels boscos joves de pi negre del Parc Nacional d'Aigüestortes i Sant Maurici

Estudiem les característiques edàfiques del sòl dels boscos joves de pi negre (Pinus uncinata) de l’estatge subalpí del Parc Nacional d’Aigüestortes i Estany de Sant Maurici corresponents a àrees de reforestació entre els anys 1956 i 2008. Aquest estudi s’ha fet de 29 parcel•les d’aquesta zona situades sobre diferents tipus de substrat, orientació i pendent. S’ha caracteritzat el sòl a partir de l’anàlisi de textura, matèria orgànica, nitrogen total, fòsfor, sodi, potassi, magnesi, calci, capacitat d’intercanvi catiònic, acidesa del sòl, relació C/N. Els resultats confirmen que es tracta de sòls àcids amb un elevat contingut de matèria orgànica a l’horitzó superficial (0-5 cm) i majoritàriament tenen humus de tipus moder. Això fa que aquest tingui valors de nitrogen total elevats. Gràcies al pH àcid i els continguts de potassi, calci i magnesi tindrem una bona fertilitat ja que la solubilitat i assimilació dels nutrients del sòl serà bona. Tots els valors obtinguts disminueixen en profunditat i mostren una gran variabilitat entre les parcel•les estudiades.

Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis.

Two different theories of migraine aura exist: In the vascular theory of Wolff, intracerebral vasoconstriction causes migraine aura via energy deficiency, whereas in the neuronal theory of Leão and Morison, spreading depression (SD) initiates the aura. Recently, it has been shown that the cerebrovascular constrictor endothelin-1 (ET-1) elicits SD when applied to the cortical surface, a finding that could provide a bridge between the vascular and the neuronal theories of migraine aura. Several arguments support the notion that ET-1-induced SD results from local vasoconstriction, but definite proof is missing. If ET-1 induces SD via vasoconstriction/ischemia, then neuronal damage is likely to occur, contrasting with the fact that SD in the otherwise normal cortex is not associated with any lesion. To test this hypothesis, we have performed a comprehensive histologic study of the effects of ET-1 when applied topically to the cerebral cortex of halothane-anesthetized rats. Our assessment included histologic stainings and immunohistochemistry for glial fibrillary acidic protein, heat shock protein 70, and transferase dUTP nick-end labeling assay. During ET-1 application, we recorded (i) subarachnoid direct current (DC) electroencephalogram, (ii) local cerebral blood flow by laser-Doppler flowmetry, and (iii) changes of oxyhemoglobin and deoxyhemoglobin by spectroscopy. At an ET-1 concentration of 1 muM, at which only 6 of 12 animals generated SD, a microarea with selective neuronal death was found only in those animals demonstrating SD. In another five selected animals, which had not shown SD in response to ET-1, SD was triggered at a second cranial window by KCl and propagated from there to the window exposed to ET-1. This treatment also resulted in a microarea of neuronal damage. In contrast, SD invading from outside did not induce neuronal damage in the absence of ET-1 (n = 4) or in the presence of ET-1 if ET-1 was coapplied with BQ-123, an ET(A) receptor antagonist (n = 4). In conclusion, SD in presence of ET-1 induced a microarea of selective neuronal necrosis no matter where the SD originated. This effect of ET-1 appears to be mediated by the ET(A) receptor.

A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia.

BACKGROUND: Mutations in SCN4A may lead to myotonia. METHODS: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. RESULTS: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene (SCN4A) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na(v)1.4 alpha subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (-12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by -8.7 mV and accelerated the entry to this state. CONCLUSIONS: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

Enhanced radar precipitation estimates using a combined clutter and beam blockage correction technique

Weather radar observations are currently the most reliable method for remote sensing of precipitation. However, a number of factors affect the quality of radar observations and may limit seriously automated quantitative applications of radar precipitation estimates such as those required in Numerical Weather Prediction (NWP) data assimilation or in hydrological models. In this paper, a technique to correct two different problems typically present in radar data is presented and evaluated. The aspects dealt with are non-precipitating echoes - caused either by permanent ground clutter or by anomalous propagation of the radar beam (anaprop echoes) - and also topographical beam blockage. The correction technique is based in the computation of realistic beam propagation trajectories based upon recent radiosonde observations instead of assuming standard radio propagation conditions. The correction consists of three different steps: 1) calculation of a Dynamic Elevation Map which provides the minimum clutter-free antenna elevation for each pixel within the radar coverage; 2) correction for residual anaprop, checking the vertical reflectivity gradients within the radar volume; and 3) topographical beam blockage estimation and correction using a geometric optics approach. The technique is evaluated with four case studies in the region of the Po Valley (N Italy) using a C-band Doppler radar and a network of raingauges providing hourly precipitation measurements. The case studies cover different seasons, different radio propagation conditions and also stratiform and convective precipitation type events. After applying the proposed correction, a comparison of the radar precipitation estimates with raingauges indicates a general reduction in both the root mean squared error and the fractional error variance indicating the efficiency and robustness of the procedure. Moreover, the technique presented is not computationally expensive so it seems well suited to be implemented in an operational environment.

Improving QPF by blending techniques at the Meteorological Service of Catalonia

The current operational very short-term and short-term quantitative precipitation forecast (QPF) at the Meteorological Service of Catalonia (SMC) is made by three different methodologies: Advection of the radar reflectivity field (ADV), Identification, tracking and forecasting of convective structures (CST) and numerical weather prediction (NWP) models using observational data assimilation (radar, satellite, etc.). These precipitation forecasts have different characteristics, lead time and spatial resolutions. The objective of this study is to combine these methods in order to obtain a single and optimized QPF at each lead time. This combination (blending) of the radar forecast (ADV and CST) and precipitation forecast from NWP model is carried out by means of different methodologies according to the prediction horizon. Firstly, in order to take advantage of the rainfall location and intensity from radar observations, a phase correction technique is applied to the NWP output to derive an additional corrected forecast (MCO). To select the best precipitation estimation in the first and second hour (t+1 h and t+2 h), the information from radar advection (ADV) and the corrected outputs from the model (MCO) are mixed by using different weights, which vary dynamically, according to indexes that quantify the quality of these predictions. This procedure has the ability to integrate the skill of rainfall location and patterns that are given by the advection of radar reflectivity field with the capacity of generating new precipitation areas from the NWP models. From the third hour (t+3 h), as radar-based forecasting has generally low skills, only the quantitative precipitation forecast from model is used. This blending of different sources of prediction is verified for different types of episodes (convective, moderately convective and stratiform) to obtain a robust methodology for implementing it in an operational and dynamic way.

Can a Halo CME from the limb be geoeffective?

The probability for a halo coronal mass ejection (CME) to be geoeffective is assumed to be higher the closer the CME launch site is located to the solar central meridian. However, events far from the central meridian may produce severe geomagnetic storms, like the case in April 2000. In this work, we study the possible geoeffectiveness of full halo CMEs with the source region situated at solar limb. For this task, we select all limb full halo (LFH) CMEs that occurred during solar cycle 23, and we search for signatures of geoeffectiveness between 1 and 5 days after the first appearance of each CME in the LASCO C2 field of view. When signatures of geomagnetic activity are observed in the selected time window, interplanetary data are carefully analyzed in order to look for the cause of the geomagnetic disturbance. Finally, a possible association between geoeffective interplanetary signatures and every LFH CME in solar cycle 23 is checked in order to decide on the CME's geoeffectiveness. After a detailed analysis of solar, interplanetary, and geomagnetic data, we conclude that of the 25 investigated events, there are only four geoeffective LFH CMEs, all coming from the west limb. The geoeffectiveness of these events seems to be moderate, turning to intense in two of them as a result of cumulative effects from previous mass ejections. We conclude that ejections from solar locations close to the west limb should be considered in space weather, at least as sources of moderate disturbances.

Quantification of brain glycogen concentration and turnover through localized 13C NMR of both the C1 and C6 resonances.

We have recently shown that at isotopic steady state (13)C NMR can provide a direct measurement of glycogen concentration changes, but that the turnover of glycogen was not accessible with this protocol. The aim of the present study was to design, implement and apply a novel dual-tracer infusion protocol to simultaneously measure glycogen concentration and turnover. After reaching isotopic steady state for glycogen C1 using [1-(13)C] glucose administration, [1,6-(13)C(2)] glucose was infused such that isotopic steady state was maintained at the C1 position, but the C6 position reflected (13)C label incorporation. To overcome the large chemical shift displacement error between the C1 and C6 resonances of glycogen, we implemented 2D gradient based localization using the Fourier series window approach, in conjunction with time-domain analysis of the resulting FIDs using jMRUI. The glycogen concentration of 5.1 +/- 1.6 mM measured from the C1 position was in excellent agreement with concomitant biochemical determinations. Glycogen turnover measured from the rate of label incorporation into the C6 position of glycogen in the alpha-chloralose anesthetized rat was 0.7 micromol/g/h.

Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.

Concentrations of the enantiomers of unconjugated and of total (unconjugated plus conjugated) mianserin, desmethylmianserin and 8-hydroxymianserin were measured in 12 patients before and after the introduction of carbamazepine. The dose of mianserin was 60 mg/d, carbamazepine was coadministered at 400 mg/d for 4 weeks, and blood samples were taken at weekly intervals after the introduction of carbamazepine. Each week, carbamazepine significantly decreased plasma concentrations of unconjugated and total (S)-mianserin (the more potent enantiomer) and of unconjugated and total (R)-mianserin. On average, plasma concentrations of unconjugated and total (S)-mianserin and of unconjugated and total (R)-mianserin were 55%, 56%, 66%, and 55%, respectively, of the corresponding values before introduction of carbamazepine. These results strongly suggest the involvement of CYP3A4, the major CYP enzyme induced by carbamazepine, in the metabolism of both enantiomers of mianserin. A strong decrease in the concentrations of (S)-8-hydroxymianserin was also measured (on average, the concentrations were 69% of the corresponding values before carbamazepine introduction). Conversely, plasma concentrations of unconjugated and of total (S)-desmethylmianserin, (R)-desmethylmianserin, and (R)-8-hydroxymianserin were only slightly modified by carbamazepine. From a clinical point of view, as a therapeutic window for (S)-mianserin has been recently suggested, the dose of racemic mianserin for a patient whose (S)-mianserin concentrations have been stabilized within this therapeutic window would need to be approximately doubled if carbamazepine, at 400 mg/d, is introduced as a comedication.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Late Jurassic continental flood basalt doleritic dykes in northwestern Cuba: remnants of the Gulf of Mexico opening

Accreted terranes, comprising a wide variety of Late Jurassic and Early Cretaceous igneous and sedimentary rocks are an important feature of Cuban geology. Their characterization is helpful for understanding Caribbean paleogeography. The Guaniguanico terrane (western Cuba) is formed by upper Jurassic platform sediments intruded by microgranular dolerite dykes. The geochemical characteristics of the dolerite whole rock samples and their minerals (augitic clinopyroxene, labradorite and andesine) are consistent with a tholeiitic affinity. Major and trace element concentrations as well as Nd, Sr and Pb isotopes show that these rocks also have a continental affinity. Sample chemistry indicates that these lavas are similar to a low Ti-P2O5 (LTi) variety of continental flood basalts (CFB) similar to the dolerites of Ferrar (Tasmania). They derived from mixing of a lithospheric mantle Source and an asthenopheric component similar to E-MORB with minor markers of crustal contamination and sediment assimilation. However, the small quantity of Cuban magmatic rocks, similarly to Tasmania, Antarctica and Siberia differs from other volumetrically important CFB occurrences Such as Parana and Deccan. These dolerites are dated as 165-150 Ma and were emplaced during the separation of the Yucatan block from South America. They could in fact be part of the Yucatan-South America margin through which the intrusive system was emplaced and which was later accreted to the Cretaceous arc of central Cuba and to the Palaeogene arc of eastern Cuba. These samples could therefore reflect the pre-rift stage between North and South America and the opening of the gulf of Mexico.

Ba3Yb(BO3)3 single crystals. Growth and spectroscopic characterization

We obtained Ba3Yb(BO3)3 single crystals by the flux method with solutions of the BaB2O4Na2OYb2O3 system. The evolution of the cell parameters with temperature shows a slope change at temperatures near 873 K, which may indicate a phase transition that is not observed by changes appearing in the x-ray powder patterns or by differential thermal analysis (DTA). The evolution of the diffraction patterns with the temperature shows incongruent melting at temperatures higher than 1473 K. DTA indicates that there is incongruent melting and this process is irreversible. Ba3Yb(BO3)3 has a wide transparency window from 247 to 3900 nm. We recorded optical absorption and emission spectra at room and low temperature, and we determined the splitting of Yb3+ ions. We used the reciprocity method to calculate the maximum emission cross section of 0.28 10-20 cm2 at 966 nm. The calculated lifetime of Yb3+ in Ba3Yb(BO3)3 is trad = 2.62 ms, while the measured lifetime is t = 3.80 ms.