The UK Renal Registry Advanced CKD Study: frequency of incorrect reporting of date of start of RRT

Background: A preliminary review of the UK Renal Registry (UKRR) pre-RRT study data revealed results suggesting that, for some patients, the date of start of renal replacement therapy (RRT), as reported to the UKRR, was incorrect and often significantly later than the true date of start. A more detailed study then aimed to validate a set of criteria to identify patients with an incorrect start date. Methods: Pre-RRT laboratory data were electronically extracted from 8,810 incident RRT patients from 9 UK renal centres. Any patient with a low urea (<15 mmol/L) at the start of RRT or with a substantial improvement in kidney function (either a fall in urea >10 mmol/L or rise in eGFR >2 ml/min/1.73 m) within the two months prior to RRT were considered to potentially have an incorrect date of start. In 4r/>selected centres, the electronic patient records of all patients flagged were reviewed to validate these criteria.r/>Results: Of 8,810 patients, 1,616 (18.3%) were flagged by the identification criteria as having a potentially incorrect date of start of RRT, although a single centre accounted for 41% of the total flagged cohort. Of these flagged patients, 61.7% had been assigned an incorrect date of start of haemodialysis (HD), 5.7% had evidence of acute RRT being given before the reported date of start of HDr/>and 9.2% had evidence of starting peritoneal dialysis exchanges prior to the reported date of start. Ofr/>those flagged, 10.7% had a correct date of start of RRT.r/>Conclusions: Accurate reporting of RRT episodes is vital for the analysis of time dependent studies such as survival or time to transplantation. A proportion of patients starting RRT were assigned an incorrect start date. In order to improve the accuracy of this reporting the UK Renal Registryr/>must work with renal centres and clinical staff on improving data input for the start of RRT.

Bdellovibrio predation in the presence of decoys:Three-way bacterial interactions revealed by mathematical and experimental analyses

Bdellovibrio bacteriovorus is a small, gram-negative, motile bacterium that preys upon other gram-negative bacteria, including several known human pathogens. Its predation efficiency is usually studied in pure cultures containing solely B. bacteriovorus and a suitable prey. However, in natural environments, as well as in any possible biomedical uses as an antimicrobial, Bdellovibrio is predatory in the presence of diverse decoys, including live nonsusceptible bacteria, eukaryotic cells, and cell debris. Here we gathered and mathematically modeled data from three-member cultures containing predator, prey, and nonsusceptible bacterial decoys. Specifically, we studied the rate of predation of planktonic late-log-phase Escherichia coli S17-1 prey by B. bacteriovorus HD100, both in the presence and in the absence of Bacillus subtilis nonsporulating strain 671, which acted as a live bacterial decoy. Interestingly, we found that although addition of the live Bacillus decoy did decrease the rate of Bdellovibrio predation in liquid cultures, this addition also resulted in a partially compensatory enhancement of the availability of prey for predation. This effect resulted in a higher final yield of Bdellovibrio than would be predicted for a simple inert decoy. Our mathematical model accounts for both negative and positive effects of predator-prey-decoy interactions in the closed batch environment. In addition, it informs considerations for predator dosing in any future therapeutic applications and sheds some light on considerations for modeling the massively complex interactions of real mixed bacterial populations in nature.

The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

The epidthelial sodium channel ENaC and its regulators in the epidermal permeability barrier function

The highly amiloride-sensitive epithelial sodium channel ENaC is well known to be involved in controlling whole body sodium homeostasis and lung liquid clearance. ENaC expression has also been detected in the skin of amphibians and mammals. Mice lacking ENaC expression lose rapidly weight associated with an epidermal barrier defect that develops following birth. This dehydration is accompanied with a highly abnormal lipid matrix composition and an impaired skin surface acidification. This strongly suggests a role of ENaC in the maturation of barrier function rather than in the prenatal generation of the barrier, and may be as such an important modulator for skin hydration. In parallel, gene targeting experiments of regulators of ENaC activity, membrane serine proteases, also termed channel activating proteases, like CAP1/Prss8 and matriptase/MT-SP1 by themselves have been shown to be crucial for the epidermal barrier function. In our review, we mainly focus on the role of ENaC and its regulators in the skin and discuss their importance in the epidermal permeability barrier function.

Rome, Londres et Paris: scenes contemporaines

UANL

Derecho penal y la obligación de investigar y sancionar graves violaciones de derechos humanos y el derecho internacional humanitario -especial referencia a la sentencia de la corte constitucional colombiana c-579/13-

En el presente trabajo se analiza la obligación de investigar graves violaciones de Derechos Humanos y Derecho Internacional Humanitario, a la luz de la sentencia de la Corte Constitucional Colombiana referente a la constitucionalidad del Marco Jurídico para la paz. De la aparente remisión que hace la Corte Constitucional a la Corte Interamericana de Derechos Humanos sobre el deber de investigar graves violaciones de Derechos Humanos y de Derecho Internacional Humanitario se concluye que la Corte Constitucional propone como premisa mayor una obligación que surge de una interpretación extensiva de la Convención Interamericana. De la misma forma, se estudia el tratamiento indebido del derecho aplicable a las amnistías e indultos, que se relaciona con la necesidad de evitar cualquier tipo de impunidad, cuyo concepto sirve para esclarecer cuáles son los estándares que se quiere proteger. Por último, se analiza el contexto al que se pretende aplicar dicha obligación, es decir, la justicia transicional, proponiendo un modelo interpretativo de los fines de la pena, y su aplicación por medio de la favorabilidad penal, para la justicia transicional, que sea acorde a la interpretación de la Convención Interamericana.

Small- and waiting-time behaviour of the thin-film-equation

We consider the small-time behavior of interfaces of zero contact angle solutions to the thin-film equation. For a certain class of initial data, through asymptotic analyses, we deduce a wide variety of behavior for the free boundary point. These are supported by extensive numerical simulations. © 2007 Society for Industrial and Applied Mathematics

A mathematical model of the in vitro keratinocyte response to chromium and nickel exposure

A mathematical model describing the main mechanistic processes involved in keratinocyte response to chromium and nickel has been developed and compared to experimental in vitro data. Accounting for the interactions between the metal ions and the keratinocytes, the law of mass action was used to generate ordinary differential equations which predict the time evolution and ion concentration dependency of keratinocyte viability, the amount of metal associated with the keratinocytes and the release of cytokines by the keratinocytes. Good agreement between model predictions and existing experimental data of these endpoints was observed, supporting the use of this model to explore physiochemical parameters that influence the toxicological response of keratinocytes to these two metals.

Effect of media polarity on the photoisomerisation of substituted stilbene, azobenzene and imine chromophores

The influence of substituents and media polarity on the photoinducedE→Z geometrical isomerisation of the stilbene, azobenzene and N-benzylideneaniline chromophores has been compared and assessed. The efficiency of the process in all three systems is markedly dependent on the presence and characteristics of electron-donor and electron-acceptor substituents at the 4- and 4′-positions. The results are discussed in terms of relaxation of the E-excited singlet state. In the absence of a nitro substituent, relaxation to the S1 orthogonal state competes effectively with non-productive intramolecular electron transfer; in the presence of a nitro substituent, the T1 orthogonal state is formed from inter-system crossing. For systems with a 4-nitro and a 4′-electron-donor substituent, access to the triplet state is inhibited by polar solvents promoting formation of the inactive charge-transfer state from the S1 state, and no isomerisation is observed. Similar effects are observed in both solution and polymer films. Such variations in behaviour have important implications for the utilisation of the chromophores in nonlinear optical phenomena including photorefractivity.

Multiwavelength Observations of EXO 0748-676. II. Emission-Line Behavior

We present optical and ultraviolet spectra, light curves, and Doppler tomograms of the low-mass X-ray binary EXO 0748-676. Using an extensive set of 15 emission-line tomograms, we show that, along with the usual emission from the stream and ``hot spot,'' there is extended nonaxisymmetric emission from the disk rim. Some of the emission and Hα and Hβ absorption features lend weight to the hypothesis that part of the stream overflows the disk rim and forms a two phase medium. The data are consistent with a 1.35 Msolar neutron star with a main-sequence companion and hence a mass ratio q~0.34.

The effect of the magnetic field of the secondary star in dwarf novae

We investigate the effect of a secondary star magnetic field on the accretion disc dynamics of dwarf novae. Simulations have been carried out with a particle code and a dipolar magnetic field structure. The magnetic field acts to remove angular momentum from the disc material, increasing the inward mass flow. This makes the accretion disc more centrally condensed, causing a reduction in the recurrence time for dwarf nova outbursts. We have produced Doppler tomograms and light curves which may be compared with observations. These tomograms are significantly different from those produced in the absence of a magnetic field on the secondary. We derive an upper limit to the magnetic moment of the secondary star in UGem of mu_2<2x10^32 A m^2. The magnetic truncation of the accretion disc produces resonance phenomena similar to those seen in the superoutbursts of SUUMa systems. While these have not been observed for systems like UGem, observations of the SUUMa systems provide us with a useful diagnostic of the disc-field interaction. We are able to place an upper limit on the magnetic moment of the secondary in ZCha of mu_2<1x10^30 A m^2.