Haemodialysis activates phospholipase A2 enzyme

Background Clinical and experimental evidence suggest that haemodialysis (HD) procedure is an inflammatory process. For the production of proinflammatory lipid mediators in many inflammatory reactions, the release of arachidonic acid by phospholipase A2 (PLA2 enzyme is a prerequisite. Therefore, the purpose of the present investigation was to establish whether the activity of PLA2 increases during HD and whether the increase depends on the type of dialyser used. Methods We performed dialysis in eight chronic HD patients. Blood samples entering and leaving the dialyser were obtained before and at 15, 60, 120 and 180 min after the dialysis was started, on one occasion using a cuprophane and on another occasion a cellulose triacetate dialyser. PLA2 activity was assessed in crude plasma and in plasma extract. Results PLA2 activity in plasma extract exhibited similar biochemical properties to that of inflammatory human synovial fluid PLA2 enzyme which is of group II PLA2. PLA2 activity in crude plasma represents a type of PLA2 other than the synovial type. In HD patients, baseline PLA2 activities in crude plasma and plasma extract were significantly increased when compared to normal subjects. An increase in PLA2 activity was observed in crude plasma with a peak appearing at 15 min when the patients were dialysed with cuprophane and cellulose triacetate membranes. This increase was observed in both arterial and venous blood samples and was more pronounced when the patients were dialysed with cuprophane than with cellulose triacetate membranes. When PLA2 was assessed in plasma extract, the activity increased only with cuprophane but not with cellulose triacetate membranes. Conclusions PLA2 activity in plasma is increased in HD patients and increases during the dialysis procedure to a greater extent with a less biocompatible membrane. Continuous activation of PLA2 might be relevant for long-term deleterious consequences of H

Efficacy and safety of secukinumab for the treatment of severe ABCA12 deficiency‐related ichthyosis in a child

Summary Background Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL‐17A inhibitor, has shown clinical efficacy in patients with moderate‐to‐severe plaque psoriasis. Aims To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP‐binding cassette subfamily A member 12 deficiency‐related severe erythrodermic ARCI. Materials & Methods 6‐months therapeutic trial. During the first 4‐weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20‐weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks. Result & Discussion After the 6‐months therapy period, there was a 48% reduction from the baseline Ichthyosis‐Area‐Severity‐Index (‐Erythema/‐Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte‐derived proinflammatory cytokines and an abrogation of Th17‐skewing during therapy. Conclusion Further studies are needed to evaluate the effects of the use of IL‐17A inhibition in ARCI patients

Formation of Nuclear Spirals in Barred Galaxies

We have performed smoothed particle hydrodynamics (SPH) simulations for the response of the gaseous disk to the imposed moderately strong non-axisymmetric potentials. The model galaxies are composed of the three stellar components (disk, bulge and bar) and two dark ones (supermassive black hole and halo) whose gravitational potentials are assumed to be invariant in time in the frame corotating with the bar. We found that the torques alone generated by the moderately strong bar that gives the maximum of tangential-to-radial force ratio as $(F_{Tan}/F_{Rad})_{max}= 0.3$ are not sufficient to drive the gas particles close to the center due to the barrier imposed by the inner Lindblad resonances (ILRs). In order to transport the gas particles towards the nucleus ($r<100$ pc), a central supermassive black hole (SMBH) and high sound speed of the gas are required to be present. The former is required to remove the inner inner Lindblad resonance (IILR) that prevents gas inflow close to the nucleus, while the latter provides favourable conditions for the gas particles to lose their angular momentum and to spiral in. Our models that have no IILR show the trailing nuclear spirals whose innermost parts reach close to the center in a curling way when the gas sound speed is $c_{s} \gtrsim 15$ km s$^{-1}$. They resemble the symmetric two-armed nuclear spirals observed in the central kiloparsec of spiral galaxies. We found that the symmetric two-armed nuclear spirals are formed by the hydrodynamic spiral shocks caused by the gravitational torque of the bar in the presence of a central SMBH that can remove IILR when the sound speed of gas is high enough to drive a large amount of gas inflow deep inside the ILR. However, the detailed morphology of nuclear spirals depends on the sound speed of gas.Comment: 38 pages, 10 figures, accepted for publication in Ap

The large scale dust lanes of the Galactic bar

(abridged) By comparing the distribution of dust and gas in the central regions of the Galaxy, we aim to obtain new insights into the properties of the offset dust lanes leading the bar's major axis in the Milky Way. On the one hand, the molecular emission of the dust lanes is extracted from the observed CO l-b-V distribution according to the interpretation of a dynamical model. On the other hand, a three dimensional extinction map of the Galactic central region constructed from near-infrared observations is used as a tracer of the dust itself and clearly reveals dust lanes in its face-on projection. Comparison of the position of both independent detections of the dust lanes is performed in the (l, b) plane. These two completely independent methods are used to provide a coherent picture of the dust lanes in the Milky Way bar. In both the gas and dust distributions, the dust lanes are found to be out of the Galactic plane, appearing at negative latitudes for l > 0 deg and at positive latitudes for l < 0 deg. However, even though there is substantial overlap between the two components, they are offset from one another with the dust appearing to lie closer to the b = 0 deg plane. Two scenarios are proposed to explain the observed offset. The first involves grain destruction by the bar shock and reformation downstream. Due to the decrease in velocity caused by the shock, this occurs at lower z. The second assumes that the gas and dust remain on a common tilted plane, but that the molecular gas decouples from the Milky Way's magnetic field, itself strong enough to resist the shear of the bar's shock. The diffuse gas and dust remain coupled to the field and are carried further downstream. This second scenario has recently been suggested in order to explain observations of the barred galaxy NGC 1097.Comment: 4 pages, 5 figures, accepted for publication in Astronomy and Astrophysics letter

Can We Reduce Negative Blood Cultures With Clinical Scores and Blood Markers? Results From an Observational Cohort Study

Only a small proportion of blood cultures routinely performed in emergency department (ED) patients is positive. Multiple clinical scores and biomarkers have previously been examined for their ability to predict bacteremia. Conclusive clinical validation of these scores and biomarkers is essential.This observational cohort study included patients with suspected infection who had blood culture sampling at ED admission. We assessed 5 clinical scores and admission concentrations of procalcitonin (PCT), C-reactive protein (CRP), lymphocyte and white blood cell counts, the neutrophil-lymphocyte count ratio (NLCR), and the red blood cell distribution width (RDW). Two independent physicians assessed true blood culture positivity. We used logistic regression models with area under the curve (AUC) analysis.Of 1083 patients, 104 (9.6%) had positive blood cultures. Of the clinical scores, the Shapiro score performed best (AUC 0.729). The best biomarkers were PCT (AUC 0.803) and NLCR (AUC 0.700). Combining the Shapiro score with PCT levels significantly increased the AUC to 0.827. Limiting blood cultures only to patients with either a Shapiro score of </=4 or PCT < 0.1 mug/L would reduce negative sampling by 20.2% while still identifying 100% of positive cultures. Similarly, a Shapiro score </=3 or PCT <0.25 mug/L would reduce cultures by 41.7% and still identify 96.1% of positive blood cultures.Combination of the Shapiro score with admission levels of PCT can help reduce unnecessary blood cultures with minimal false negative rates.The study was registered on January 9, 2013 at the 'ClinicalTrials.gov' registration web site (NCT01768494)

The Milky Way: An Exceptionally Quiet Galaxy; Implications for the formation of spiral galaxies

[Abridged]We compare both the Milky Way and M31 galaxies to local external disk galaxies within the same mass range, using their relative locations in the planes formed by V_flat versus M_K, j_disk, and the average Fe abundance of stars in the galaxy outskirts. We find, for all relationships, that the MW is systematically offset by ~ 1 sigma, showing a significant deficiency in stellar mass, in angular momentum, in disk radius and [Fe/H] in the stars in its outskirts at a given V_flat. On the basis of their location in the M_K, V_flat, and R_d volume, the fraction of spirals like the MW is 7+/-1%, while M31 appears to be a "typical'' spiral. Our Galaxy appears to have escaped any significant merger over the last ~10 Gyrs which may explain why it is deficient by a factor 2 to 3 in stellar mass, angular momentum and outskirts metallicity and then, unrepresentative of the typical spiral. As with M31, most local spirals show evidence for a history shaped mainly by relatively recent merging. We conclude that the standard scenario of secular evolution is generally unable to reproduce the properties of most (if not all) spiral galaxies. However, the so-called "spiral rebuilding'' scenario proposed by Hammer et al. 2005 is consistent with the properties of both distant galaxies and of their descendants - the local spirals.Comment: 14 pages, 6 figures, to appear in Ap

The MACHO project: Microlensing Optical Depth towards the Galactic Bulge from Difference Image Analysis

We present the microlensing optical depth towards the Galactic bulge based on the detection of 99 events found in our Difference Image Analysis (DIA) survey. This analysis encompasses three years of data, covering ~ 17 million stars in ~ 4 deg^2, to a source star baseline magnitude limit of V = 23. The DIA technique improves the quality of photometry in crowded fields, and allows us to detect more microlensing events with faint source stars. We find this method increases the number of detection events by 85% compared with the standard analysis technique. DIA light curves of the events are presented and the microlensing fit parameters are given. The total microlensing optical depth is estimated to be tau_(total)= 2.43^(+0.39/-0.38) x 10^(-6) averaged over 8 fields centered at l=2.68 and b=-3.35. For the bulge component we find tau_(bulge)=3.23^(+0.52/-0.50) x 10^(-6) assuming a 25% stellar contribution from disk sources. These optical depths are in good agreement with the past determinations of the MACHO Alcock et al. (1997) and OGLE Udalski et al. (1994) groups, and are higher than predicted by contemporary Galactic models. We show that our observed event timescale distribution is consistent with the distribution expected from normal mass stars, if we adopt the stellar mass function of Scalo (1986) as our lens mass function. However, we note that as there is still disagreement about the exact form of the stellar mass function, there is uncertainty in this conclusion. Based on our event timescale distribution we find no evidence for the existence of a large population of brown dwarfs in the direction of the Galactic bulge.Comment: Updated references and corrected optical depth values. tau_tot= [2.91(+0.47/-0.45) -> 2.43^(+0.39/-0.38)] x 10^(-6) tau_bul = [3.88(+0.63/-0.60) -> 3.23^(+0.52/-0.50)] x 10^(-6

An inner ring and the micro lensing toward the Bulge

All current Bulge-Disk models for the inner Galaxy fall short of reproducing self-consistently the observed micro-lensing optical depth by a factor of two ($> 2\sigma$). We show that the least mass-consuming way to increase the optical depth is to add density roughly half-way the observer and the highest micro-lensing-source density. We present evidence for the existence of such a density structure in the Galaxy: an inner ring, a standard feature of barred galaxies. Judging from data on similar rings in external galaxies, an inner ring can contribute more than 50% of a pure Bulge-Disk model to the micro-lensing optical depth. We may thus eliminate the need for a small viewing angle of the Bar. The influence of an inner ring on the event-duration distribution, for realistic viewing angles, would be to increase the fraction of long-duration events toward Baade's window. The longest events are expected toward the negative-longitude tangent point at $\ell\sim$ -22\degr . A properly sampled event-duration distribution toward this tangent point would provide essential information about viewing angle and elongation of the over-all density distribution in the inner Galaxy.Comment: 9 pages, 7(15) figs, LaTeX, AJ (accepted

Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice

Dynamics of the Galactic Bulge using Planetary Nebulae

Evidence for a bar at the center of the Milky Way triggered a renewed enthusiasm for dynamical modelling of the Galactic bar-bulge. Our goal is to compare the kinematics of a sample of tracers, planetary nebulae, widely distributed over the bulge with the corresponding kinematics for a range of models of the inner Galaxy. Three of these models are N-body barred systems arising from the instabilities of a stellar disk (Sellwood, Fux and Kalnajs), and one is a Schwarzschild system constructed to represent the 3D distribution of the COBE/DIRBE near-IR light and then evolved as an N-body system for a few dynamical times (Zhao). For the comparison of our data with the models, we use a new technique developed by Saha (1998). The procedure finds the parameters of each model, i.e. the solar galactocentric distance R_o in model units, the orientation angle phi, the velocity scale (in km/s per model unit), and the solar tangential velocity which best fit the data.Comment: 48 pages (Latex), 30 figures (PS), accepted for pub. in A