The relationship between P2X4 and P2X7: a physiologically important interaction?

Purinergic signaling within the kidney is becoming an important focus in the study of renal health and disease. The effectors of ATP signaling, the P2Y and P2X receptors, are expressed to varying extents in and along the nephron. There are many studies demonstrating the importance of the P2Y2 receptor on kidney function, and other P2 receptors are now emerging as participants in renal regulation. The P2X4 receptor has been linked to epithelial sodium transport in the nephron and expression levels of the P2X7 receptor are up-regulated in certain pathophysiological states. P2X7 antagonism has been shown to ameliorate rodent models of DOCA salt-induced hypertension and P2X4 null mice are hypertensive. Interestingly, polymorphisms in the genetic loci of P2X4 and P2X7 have been linked to blood pressure variation in human studies. In addition to the increasing evidence linking these two P2X receptors to renal function and health, a number of studies link the two receptors in terms of physical associations between their subunits, demonstrated both in vitro and in vivo. This review will analyze the current literature regarding interactions between P2X4 and P2X7 and assess the potential impact of these with respect to renal function

Single walled carbon nanotube channel flow electrode : hydrodynamic voltammetry at the nanomolar level

The use of single walled carbon nanotube (SWNT) band electrodes in a channel flow cell, for low concentration detection, with hydrodynamic voltammetry is reported. A two dimensional SWNT network electrode is combined with a one piece channel flow cell unit, fabricated by microstereolithography. This configuration provides well defined hydrodynamics over a wide range of volume flow rates (0.05–25 mL min− 1). Limiting current measurements, from linear sweep voltammograms, are in good agreement with the channel electrode Levich equation, for the one electron oxidation of ferrocenylmethyl trimethylammonium (FcTMA+), over a wide concentration range, 1 × 10− 8 M to 2.1 × 10− 5 M, with a detection limit of 5 nM. At the highest flow rates, some influence of the slightly recessed electrode geometry arising from the SWNT electrode fabrication is noted. However, this can be accounted for by a full simulation of the hydrodynamics and solution of the resulting convection–diffusion equation. Application of this hydrodynamic configuration to the voltammetric detection of dopamine is also demonstrated

Space VLBI Observations of 3C 279 at 1.6 and 5 GHz

We present the first VLBI Space Observatory Programme (VSOP) observations of the gamma-ray blazar 3C 279 at 1.6 and 5 GHz. The combination of the VSOP and VLBA-only images at these two frequencies maps the jet structure on scales from 1 to 100 mas. On small angular scales the structure is dominated by the quasar core and the bright secondary component `C4' located 3 milliarcseconds from the core (at this epoch). On larger angular scales the structure is dominated by a jet extending to the southwest, which at the largest scale seen in these images connects with the smallest scale structure seen in VLA images. We have exploited two of the main strengths of VSOP: the ability to obtain matched-resolution images to ground-based images at higher frequencies and the ability to measure high brightness temperatures. A spectral index map was made by combining the VSOP 1.6 GHz image with a matched-resolution VLBA-only image at 5 GHz from our VSOP observation on the following day. The spectral index map shows the core to have a highly inverted spectrum, with some areas having a spectral index approaching the limiting value for synchrotron self-absorbed radiation of 2.5. Gaussian model fits to the VSOP visibilities revealed high brightness temperatures (>10^{12} K) that are difficult to measure with ground-only arrays. An extensive error analysis was performed on the brightness temperature measurements. Most components did not have measurable brightness temperature upper limits, but lower limits were measured as high as 5x10^{12} K. This lower limit is significantly above both the nominal inverse Compton and equipartition brightness temperature limits. The derived Doppler factor, Lorentz factor, and angle to the line-of-sight in the case of the equipartition limit are at the upper end of the range of expected values for EGRET blazars.Comment: 11 pages, 6 figures, emulateapj.sty, To be published in The Astrophysical Journal, v537, Jul 1, 200

Assessing predictive performance of published population pharmacokinetic models of intravenous tobramycin in pediatric patients

Several population pharmacokinetic models describe the dose-exposure relationship of tobramycin in pediatric patients. Before the implementation of these models in clinical practice for dosage adjustment, their predictive performance should be externally evaluated. This study tested the predictive performance of all published population pharmacokinetic models of tobramycin developed for pediatric patients with an independent patient cohort. A literature search was conducted to identify suitable models for testing. Demographic and pharmacokinetic data were collected retrospectively from the medical records of pediatric patients who had received intravenous tobramycin. Tobramycin exposure was predicted from each model. Predictive performance was assessed by visual comparison of predictions to observations, by calculation of bias and imprecision, and through the use of simulation-based diagnostics. Eight population pharmacokinetic models were identified. A total of 269 concentration-time points from 41 pediatric patients with cystic fibrosis were collected for external evaluation. Three models consistently performed best in all evaluations and had mean errors ranging from −0.4 to 1.8 mg/liter, relative mean errors ranging from 4.9 to 29.4%, and root mean square errors ranging from 47.8 to 66.9%. Simulation-based diagnostics supported these findings. Models that allowed a two-compartment disposition generally had better predictive performance than those that used a one-compartment disposition model. Several published models of the pharmacokinetics of tobramycin showed reasonable low levels of bias, although all models seemed to have some problems with imprecision. This suggests that knowledge of typical pharmacokinetic behavior and patient covariate values alone without feedback concentration measurements from individual patients is not sufficient to make precise predictions

Disciplined doctors: Does the sex of a doctor matter? A cross-sectional study examining the association between a doctor's sex and receiving sanctions against their medical registration.

To examine the association between doctors' sex and receiving sanctions on their medical registration, while controlling for other potentially confounding variables

Cerebellar Abiotrophy in Two Related Lion-tailed Macaques (Macaca silenus)

Cerebellar abiotrophy is a degenerative condition characterized by either early or late onset of severe neurological deficits caused by the marked depletion of Purkinje cells and granule cell neurons of the cerebellar cortex. The condition has been reported in numerous species with a proposed genetic basis of transmission. Here we present the anatomopathological investigation of two closely related lion-tailed macaques. Both cases, a 9-month-old male and a 4-month-old female, shared a long history of progressively worsening ataxia, incoordination and delayed body growth. Based on the characteristic findings, diagnoses of cerebellar abiotrophy were made. The relatedness of the two cases strongly supports an inherited mode of transmission. To the authors’ knowledge, this is the first report of cerebellar abiotrophy in a macaque species

The Stellar Population of the M31 Spiral Arm Around OB Association A24

A study of the stellar population of the M31 spiral arm around OB association A24 was carried out based on the photometric data obtained from deep V and JHK imaging. The luminosity function was obtained for -7 <~ Mbol <~ -3.5 by applying the extinction correction corresponding to Av=1 and the bolometric correction BC(K) as an empirical function of (J-K)o. In comparing the observed color-luminosity diagrams with semitheoretical isochrones modified for the dust-shell effects, we found the young population of t <~ 30 Myr with supergiants of Mbol <~ -5, the bulk of the intermediate-age population of t ~ 0.2 - 2.5 Gyr with bright asymptotic giant branch (AGB) stars of -5 <~ Mbol <~ -4, and old populations of t ~> 3 Gyr with AGB and red giant branch (RGB) stars of Mbol ~> -4. The average star formation rate was estimated to be ~1.8x10^4 M_o/Myr and ~0.7x10^4 M_o/Myr per deprojected disk area of 1 kpc^2 from the number density of B0 V stars around Mv=-4.0 (age ~10 Myr) and the number density of bright AGB stars around Mbol = -4.3 (age ~1 Gyr), respectively. A study of the local variation in the V and the J and H luminosity functions revealed a kind of anticorrelation between the population of the young component and that of the intermediate-age component when subdomains of ~100 pc scales were concerned. This finding suggests that the disk domain around the A24 area experienced a series of star formation episodes alternatively among different subdomains with a timescale of a few spiral passage periods. Brief discussions are given about the interstellar extinction and about the lifetimes of bright AGB stars and the highly red objects (HROs) in the same area.Comment: 27 pages, 11 figures, accepted: ApJ, July 1, 199

Sex differences in medico-legal action against doctors: a systematic review and meta-analysis

The relationship between male sex and poor performance in doctors remains unclear, with high profile studies showing conflicting results. Nevertheless, it is an important first step towards understanding the causes of poor performance in doctors. This article aims to establish the robustness of the association between male sex and poor performance in doctors, internationally and over time