Switch to Sirolimus-based immunosuppresion in stable renal transplant recipients

Purpose: Sirolimus (SRL) has been used to replace calcineurin inhibitors (CNI) for various indications including CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of switching from CNI to SRL in stable renal transplant recipients (RTR) with low grade proteinuria (<1 g/24 h). Methods and materials: Between 2001 and 2007, 41 patients (20 females, 21 males; mean age 47 ± 13) were switched after a median time post-transplantation of 73.5 months (range 0.2-273.2 months). Indications for switch were CNI nephrotoxicity (39%), thrombotic micro-angiopathy (14.6%), post-transplantation cancer (24.4%), CNI neurotoxicity (7.4%), or others (14.6%). Mean follow-up after SRL switch was 23.8±16.3 months. Mean SRL dosage and through levels were 2.4 ± 1.1 mg/day and 8 ± 2.2 ug/l respectively. Immunosuppressive regiments were SRL + mycophenolate mofetil (MMF) (31.7%), SRL + MMF + prednisone (36.58%), SRL + prednisone (19.51%), SRL + Azathioprine (9.75%), or SRL alone (2.43%). Results: Mean creatinine decreased from 164 to 143 μmol/l (p <0.03), mean estimated glomerular filtration rate (eGFR) increased significantly from 50.13 to 55.01 ml/minute (p <0.00001), mean systolic and diastolic blood pressure decreased from 138 to 132 mm Hg (p <0.03) and from 83 to78 mm Hg (p <0.01), but mean proteinuria increased from 0.21 to 0.63 g/24 h (p <0.001). While mean total cholesterolemia didn't increased significantly from 5.09 to 5.56 mmol/l (p = 0.06). The main complications after SRL switch were dermatitis (19.5%), urinary tract infections (24.4%), ankle edema (13.3%), and transient oral ulcers (20%). Acute rejection after the switch occurred in 7.3% of patients (n = 3), and 2 acute rejections were successfully treated with corticosteroids and 1 did not respond to treatment (not related to switch). SRL had to be discontinued in 17% of patients (2 nephrotic syndromes, 2 severe edema, 1 acute rejection, 1 thrombotic micro-angiopathy, and 1 fever). Conclusion: In conclusion, we found that switching from CNI to SRL in stable RTR was safe and associated with a significant improvement of renal function and blood pressure. Known side-effects of SRL led to drug discontinuation in less than 20% of patients and the acute rejection rate was 7.3%. This experience underlines the importance of patient selection before switching to SRL, in particular regarding preswitch proteinuria.

Stable isotope composition of smectite in suevites at the Ries crater, Germany: Implications for hydrous alteration of impactites

The 24-km diameter Ries crater, Germany, exhibits well-preserved crater filling and surficial melt-rich breccia deposits that are believed to have been altered by post-impact hydrothermal fluids. The alteration mineralogy of the crater filling breccias is characterized by clay (smectite, chlorite) and a zeolite assemblage, and secondary clay phases (smectite, minor halloysite) in surficial melt-bearing breccia deposits. Using stable isotope analysis of secondary smectitic clay fractions, evidence of significant hydrous alteration of impactites at large water/rock ratios was found. The estimated fluid temperatures, using data derived by delta(18)O and delta D fractionation, suggest smectite precipitation in surficial breccias in equilibrium with meteoric fluids at temperatures 16 +/- 5 degrees C in agreement with the long-term variation of modern precipitation in the area. The stable isotope composition of smectite in crater-fill breccia, however, suggests a trend of monotonously increasing temperatures from 43 to 112 degrees C. with increasing depth through the breccia sequence. This demonstrates a different origin of alteration and temperature distribution for the surficial and crater filling melt-bearing impact breccias in the Ries crater. Our results suggest that the inverted structure of hydrothermal systems observed in some terrestrial impact craters, including the Ries crater, could indicate the initial configuration of a thermal anomaly in the crater filling sequence, but which is replaced with a normal hydrothermal convection in crater proper, during the course of post-impact cooling. (C) 2010 Elsevier B.V. All rights reserved.

The role of attention in multisensory integration processes

Report for the scientific sojourn at the University of Queensland, Australia, between June to October 2007. The integration of sensory information coming from different modalities is a subjectively effortless and automatic process. However, recent findings converge on the idea that there might be some limitations on how much multisensory information can our brains integrate at a given moment. The overall objective of this research visit was to expand and reinforce our current line of research addressing the role that attention plays on the mechanisms responsible for multisensory integration. There is also a critical review of the literature as well as a list of research questions of potential interest in the area of the neuropsychology of multisensory attention.

Genetic diversity and differentiation processes in the ploidy series of Olea europaea L.: a multiscale approach from subspecies to insular populations.

Geographical isolation and polyploidization are central concepts in plant evolution. The hierarchical organization of archipelagos in this study provides a framework for testing the evolutionary consequences for polyploid taxa and populations occurring in isolation. Using amplified fragment length polymorphism and simple sequence repeat markers, we determined the genetic diversity and differentiation patterns at three levels of geographical isolation in Olea europaea: mainland-archipelagos, islands within an archipelago, and populations within an island. At the subspecies scale, the hexaploid ssp. maroccana (southwest Morocco) exhibited higher genetic diversity than the insular counterparts. In contrast, the tetraploid ssp. cerasiformis (Madeira) displayed values similar to those obtained for the diploid ssp. guanchica (Canary Islands). Geographical isolation was associated with a high genetic differentiation at this scale. In the Canarian archipelago, the stepping-stone model of differentiation suggested in a previous study was partially supported. Within the western lineage, an east-to-west differentiation pattern was confirmed. Conversely, the easternmost populations were more related to the mainland ssp. europaea than to the western guanchica lineage. Genetic diversity across the Canarian archipelago was significantly correlated with the date of the last volcanic activity in the area/island where each population occurs. At the island scale, this pattern was not confirmed in older islands (Tenerife and Madeira), where populations were genetically homogeneous. In contrast, founder effects resulted in low genetic diversity and marked genetic differentiation among populations of the youngest island, La Palma.

Testing the TASP: An Experimental Investigation of Learning in Games with Unstable Equilibria

We report experiments designed to test between Nash equilibria that are stable and unstable under learning. The “TASP” (Time Average of the Shapley Polygon) gives a precise prediction about what happens when there is divergence from equilibrium under fictitious play like learning processes. We use two 4 x 4 games each with a unique mixed Nash equilibrium; one is stable and one is unstable under learning. Both games are versions of Rock-Paper-Scissors with the addition of a fourth strategy, Dumb. Nash equilibrium places a weight of 1/2 on Dumb in both games, but the TASP places no weight on Dumb when the equilibrium is unstable. We also vary the level of monetary payoffs with higher payoffs predicted to increase instability. We find that the high payoff unstable treatment differs from the others. Frequency of Dumb is lower and play is further from Nash than in the other treatments. That is, we find support for the comparative statics prediction of learning theory, although the frequency of Dumb is substantially greater than zero in the unstable treatments.

A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance.

Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer.

Does Semantic Context Benefit Speech Understanding through "Top-Down" Processes? Evidence from Time-resolved Sparse fMRI.

When speech is degraded, word report is higher for semantically coherent sentences (e.g., her new skirt was made of denim) than for anomalous sentences (e.g., her good slope was done in carrot). Such increased intelligibility is often described as resulting from "top-down" processes, reflecting an assumption that higher-level (semantic) neural processes support lower-level (perceptual) mechanisms. We used time-resolved sparse fMRI to test for top-down neural mechanisms, measuring activity while participants heard coherent and anomalous sentences presented in speech envelope/spectrum noise at varying signal-to-noise ratios (SNR). The timing of BOLD responses to more intelligible speech provides evidence of hierarchical organization, with earlier responses in peri-auditory regions of the posterior superior temporal gyrus than in more distant temporal and frontal regions. Despite Sentence content × SNR interactions in the superior temporal gyrus, prefrontal regions respond after auditory/perceptual regions. Although we cannot rule out top-down effects, this pattern is more compatible with a purely feedforward or bottom-up account, in which the results of lower-level perceptual processing are passed to inferior frontal regions. Behavioral and neural evidence that sentence content influences perception of degraded speech does not necessarily imply "top-down" neural processes.

Innovative method for carbon dioxide determination in human postmortem cardiac gas samples using headspace-gas chromatography-mass spectrometry and stable labeled isotope as internal standard.

A novel approach to measure carbon dioxide (CO2) in gaseous samples, based on a precise and accurate quantification by (13)CO2 internal standard generated in situ is presented. The main goal of this study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable in the routine determination of CO2. The main drawback of the GC methods discussed in the literature for CO2 measurement is the lack of a specific internal standard necessary to perform quantification. CO2 measurement is still quantified by external calibration without taking into account analytical problems which can often occur considering gaseous samples. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in situ an internal labeled standard gas ((13)CO2) on the basis of the stoichiometric formation of CO2 by the reaction of hydrochloric acid (HCl) with sodium hydrogen carbonate (NaH(13)CO3). This method allows a precise measurement of CO2 concentration and was validated on various human postmortem gas samples in order to study its efficiency.

Fact And Fiction In FX Arbitrage Processes

The efficient markets hypothesis implies that arbitrage opportunities in markets such as those for foreign exchange (FX) would be, at most, short-lived. The present paper surveys the fragmented nature of FX markets, revealing that information in these markets is also likely to be fragmented. The “quant” workforce in the hedge fund featured in The Fear Index novel by Robert Harris would have little or no reason for their existence in an EMH world. The four currency combinatorial analysis of arbitrage sequences contained in Cross, Kozyakin, O’Callaghan, Pokrovskii and Pokrovskiy (2012) is then considered. Their results suggest that arbitrage processes, rather than being self-extinguishing, tend to be periodic in nature. This helps explain the fact that arbitrage dealing tends to be endemic in FX markets.

Fact And Fiction In FX Arbitrage Processes

The efficient markets hypothesis implies that arbitrage opportunities in markets such as those for foreign exchange (FX) would be, at most, short-lived. The present paper surveys the fragmented nature of FX markets, revealing that information in these markets is also likely to be fragmented. The “quant” workforce in the hedge fund featured in The Fear Index novel by Robert Harris would have little or no reason for their existence in an EMH world. The four currency combinatorial analysis of arbitrage sequences contained in Cross, Kozyakin, O’Callaghan, Pokrovskii and Pokrovskiy (2012) is then considered. Their results suggest that arbitrage processes, rather than being self-extinguishing, tend to be periodic in nature. This helps explain the fact that arbitrage dealing tends to be endemic in FX markets.

Nano-electro-mechanical in dynamical cellular processes

Report for the scientific sojourn carried out at the Department of Structure and Constituents of Matter during 2007.The main focus of the work was on phenomena related to nano-electromechanical processes that take place on a cellular level. Additionally, it has also been performed independent work related to charge and energy transfer in bio molecules, energy transfer in coupled spin systems as well as electrodynamics of nonlinear metamaterials.

Fact And Fictions In FX Arbitrage Processes

The efficient markets hypothesis implies that arbitrage opportunities in markets such as those for foreign exchange (FX) would be, at most, short-lived. The present paper surveys the fragmented nature of FX markets, revealing that information in these markets is also likely to be fragmented. The “quant” workforce in the hedge fund featured in The Fear Index novel by Robert Harris would have little or no reason for their existence in an EMH world. The four currency combinatorial analysis of arbitrage sequences contained in Cross, Kozyakin, O’Callaghan, Pokrovskii and Pokrovskiy (2012) is then considered. Their results suggest that arbitrage processes, rather than being self-extinguishing, tend to be periodic in nature. This helps explain the fact that arbitrage dealing tends to be endemic in FX markets.