Costimulatory blockade: A novel approach to the treatment of glomerular disease?

Costimulatory pathways (Cluster of differentiation 28, tumor necrosis factor-related, adhesion and T Cell Ig- and mucin-domain molecules) regulating the interactions between receptors on the T cells and their ligands expressed on several cell types, have a key role in controlling many immunological and non immunological processes. Indeed, accumulating evidence indicate that these molecules are involved in the pathogenesis of numerous conditions, such as allograft rejection, atherosclerosis, rheumatoid arthritis, psoriasis and renal diseases, including glomerulonephritis. Primary or secondary (i.e., associated with infections, drugs or systemic diseases, such as systemic lupus erythematosus, diabetes, etc.) glomerulonephritis represent a group of heterogeneous diseases with different pathogenic mechanisms. Since costimulatory molecules, in particular CD80 and CD40, have been found to be expressed on podocytes in the course of different experimental and clinical glomerulonephritis, costimulation has been thought as a new therapeutic target for patients with glomerular diseases. However, although experimental data suggested that the blockade of costimulatory pathways is effective and safe in the prevention and treatment of glomerular diseases, clinical trials reported contrasting results. So, at this moment, there is not a strong evidence for the general use of costimulatory blockade as an alternative treatment strategy in patients with primary or secondary glomerulonephritis. Here, we critically discuss the current data and the main issues regarding the development of this innovative therapeutic approach

Detecting binary compact-object mergers with gravitational waves: Understanding and Improving the sensitivity of the PyCBC search

We present an improved search for binary compact-object mergers using a network of ground-based gravitational-wave detectors. We model a volumetric, isotropic source population and incorporate the resulting distribution over signal amplitude, time delay, and coalescence phase into the ranking of candidate events. We describe an improved modeling of the background distribution, and demonstrate incorporating a prior model of the binary mass distribution in the ranking of candidate events. We find a $\sim 10\%$ and $\sim 20\%$ increase in detection volume for simulated binary neutron star and neutron star--binary black hole systems, respectively, corresponding to a reduction of the false alarm rates assigned to signals by between one and two orders of magnitude.Comment: 7 pages, 3 figures, as accepted by Ap

A stochastic template bank for gravitational wave searches for precessing neutron star - black hole coalescence events

Gravitational wave searches to date have largely focused on non-precessing systems. Including precession effects greatly increases the number of templates to be searched over. This leads to a corresponding increase in the computational cost and can increase the false alarm rate of a realistic search. On the other hand, there might be astrophysical systems that are entirely missed by non-precessing searches. In this paper we consider the problem of constructing a template bank using stochastic methods for neutron star - black hole binaries allowing for generic precession, but with the restriction that the total angular momentum of the binary is pointing towards the detector. We quantify the number of templates required for the search, and we explicitly construct the template bank. We show that despite the large number of templates, stochastic methods can be adapted to solve the problem. We quantify the parameter space region over which the non-precessing search might miss signals

Management of mineral metabolism in hemodialysis patients: discrepancy between interventions and perceived causes of failure

none8BACKGROUND: Mineral and bone disorders (MBD) in patients undergoing hemodialysis (HD) are a major clinical complication. Current therapeutic strategies do not attain the expected results. The Italian audit on mineral metabolism was implemented to investigate MBD management through a "patient-oriented" approach. METHODS: Clinical and laboratory data pertinent to MBD from 509 prevalent adult patients on chronic HD were recorded and examined (audit), after which individual strategies were elaborated to improve MBD control. Their effectiveness was evaluated 6 months after the audit (Post-6). RESULTS: The audit disclosed poor MBD control in a high percentage of patients (56 %). Low compliance to treatment was the major determinant of failure (in 43.5 % of cases). Logistic regression showed a direct correlation between high degree of compliance and the achievement of therapeutic targets, e.g. parathyroid hormone: odds ratio (OR) 2.48, p = 0.015. In contrast, a minority of the proposed interventions (14.7 %) included strategies to improve patient compliance. At Post-6, despite a significant increase in drug prescription (p < 0.05 vs. audit), the rate of successful MBD control was unchanged. CONCLUSIONS: Low compliance with treatment is a major, but still neglected, cause of failure in the achievement of MBD control in HD patients.Esposito, P; Rampino, T; Gregorini, M; Tinelli, C; De Silvestri, A; Malberti, F; Coppo, R; Dal Canton, A.Esposito, P; Rampino, Teresa; Gregorini, Marilena; Tinelli, C; De Silvestri, A; Malberti, F; Coppo, R; DAL CANTON, Antoni

Renal involvement in mushroom poisoning: The case of Orellanus syndrome

none8Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little-known intoxication.openEsposito, P; La Porta, E; Calatroni, M; Bianzina, S; Libetta, C; Gregorini, M; Rampino, T; Dal Canton, AEsposito, P; La Porta, E; Calatroni, M; Bianzina, S; Libetta, Carmelo; Gregorini, Marilena; Rampino, Teresa; DAL CANTON, Antoni

Analysis of Sub-threshold Short Gamma-ray Bursts in Fermi GBM Data

The Fermi Gamma-ray Burst Monitor (GBM) is currently the most prolific detector of Gamma-Ray Bursts (GRBs). Recently the detection rate of short GRBs (SGRBs) has been dramatically increased through the use of ground-based searches that analyze GBM continuous time tagged event (CTTE) data. Here we examine the efficiency of a method developed to search CTTE data for sub-threshold transient events in temporal coincidence with LIGO/Virgo compact binary coalescence triggers. This targeted search operates by coherently combining data from all 14 GBM detectors by taking into account the complex spatial and energy dependent response of each detector. We use the method to examine a sample of SGRBs that were independently detected by the Burst Alert Telescope on board the Neil Gehrels Swift Observatory, but which were too intrinsically weak or viewed with unfavorable instrument geometry to initiate an on-board trigger of GBM. We find that the search can successfully recover a majority of the BAT detected sample in the CTTE data. We show that the targeted search of CTTE data will be crucial in increasing the GBM sensitivity, and hence the gamma-ray horizon, to weak events such as GRB 170817A. We also examine the properties of the GBM signal possibly associated with the LIGO detection of GW150914 and show that it is consistent with the observed properties of other sub-threshold SGRBs in our sample. We find that the targeted search is capable of recovering true astrophysical signals as weak as the signal associated with GW150914 in the untriggered data.Comment: 10 pages, 9 figures, 1 table, submitted to Ap