Activated complement C3: A potentially novel predictor of progressive IgA nephropathy

Activated complement C3: A potentially novel predictor of progressive IgA nephropathy. In the search for a serologic marker of disease activity, we measured concentrations of activated C3 (actC3, that is, neoantigens developing after C3 activation on breakdown products), C4-C3 complexes and soluble C5b-9 (sC5b-9) in one or two plasma samples from adult patients with IgA nephropathy (IgAN, N = 50) or Henoch-Schönlein purpura (HSP, N = 4). As controls, 20 patients with non-immune renal disease, but comparable age, degree of proteinuria, renal dysfunction and prevalence of hypertension were studied. Compared to controls, actC3 levels were elevated in 30% of the patients with IgAN and one of the HSP patients. C4-C3 complexes were elevated in only 8% of the IgAN patients, and sC5b-9 levels were within the control range in all IgAN and HSP patients. In IgAN patients with elevated actC3 levels, proteinuria and hematuria were more pronounced than in those with normal levels. Elevated plasma concentrations of actC3 at the first presentation correlated with subsequent deterioration of renal function both in patients with initially normal and already impaired renal function (r = -0.56, N = 44, P = 0.003). The five IgAN patients with elevated actC3 on both occasions of obtaining plasma showed the most rapid loss of renal function. We conclude that mainly alternative pathway complement activation can be demonstrated in patients with IgAN and HSP. In IgAN patients the presence of complement activation is associated with more severe renal disease. Further studies are warranted to examine the clinical usefulness of actC3 as a predictor of the subsequent course of IgAN

Age and isotopic constraints on magmatism along the Karakoram-Kohistan Suture Zone, NW Pakistan: evidence for subduction and continued convergence after India-Asia collision

Abstract.: Detailed geological mapping in the Drosh-Shishi area in southern Chitral (NW Pakistan) was combined with high-precision U-Pb dating on zircons to constrain the timing of magmatism and associated deformation/metamorphic events related to the Kohistan-Karakoram convergence and collision. Our new ages indicate that the Mesozoic to Tertiary magmatic history of this region is influenced by long-lived melt generation above an active subduction zone. Dated intrusive rocks range in age from 130 to 39 million years, indicating that subduction-related magmatism continued after the Kohistan-Karakoram and the India-Asia collisions. Initial hafnium isotope ratios were measured on the dated zircons to constrain the type of melt source of the dated plutons. The data reveal the different nature of partly coeval magmatism in these units, i.e. continental arc magmatism in the Karakoram (ca. 130-104 Ma) and arc magmatism magmatism on the Kohistan side (112-39 Ma). Intrusions within the suture zone can be clearly traced to be Karakoram-derived on the basis of initial Hf isotopic compositions. Granite dykes crosscutting the Kohistan units have sampled an underlying, old continental basement of Gondwana affinity. The geochronological evidence presented in this paper is consistent with Cretaceous subduction beneath the Karakoram Terrane. The related calc-alkaline magmatism seems to have stopped at about 100 Ma. Granite dykes on the Kohistan side show that the magmatic and tectonic history of the Karakoram-Kohistan Suture Zone continued to the Eocene. This long tectono-metamorphic and magmatic activity in the arc plates was likely due to complex and few million year long interplays between subduction and thrusting events in the forearc, within-arc and back-arc regions between two active subduction zone

The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency

Background: Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency. Goal: To evaluate the presence of immunodeficiency in a series of 6 patients with JS. Methods: Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry. Results: Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found. Conclusions: Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS

Prospects for high-z cluster detections with Planck, based on a follow-up of 28 candidates using MegaCam@CFHT

The Planck catalogue of SZ sources limits itself to a significance threshold of 4.5 to ensure a low contamination rate by false cluster candidates. This means that only the most massive clusters at redshift z>0.5, and in particular z>0.7, are expected to enter into the catalogue, with a large number of systems in that redshift regime being expected around and just below that threshold. In this paper, we follow-up a sample of SZ sources from the Planck SZ catalogues from 2013 and 2015. In the latter maps, we consider detections around and at lower significance than the threshold adopted by the Planck Collaboration. To keep the contamination rate low, our 28 candidates are chosen to have significant WISE detections, in combination with non-detections in SDSS/DSS, which effectively selects galaxy cluster candidates at redshifts $z\gtrsim0.5$. By taking r- and z-band imaging with MegaCam@CFHT, we bridge the 4000A rest-frame break over a significant redshift range, thus allowing accurate redshift estimates of red-sequence cluster galaxies up to z~0.8. After discussing the possibility that an overdensity of galaxies coincides -by chance- with a Planck SZ detection, we confirm that 16 of the candidates have likely optical counterparts to their SZ signals, 13 (6) of which have an estimated redshift z>0.5 (z>0.7). The richnesses of these systems are generally lower than expected given the halo masses estimated from the Planck maps. However, when we follow a simplistic model to correct for Eddington bias in the SZ halo mass proxy, the richnesses are consistent with a reference mass-richness relation established for clusters detected at higher significance. This illustrates the benefit of an optical follow-up, not only to obtain redshift estimates, but also to provide an independent mass proxy that is not based on the same data the clusters are detected with, and thus not subject to Eddington bias.Comment: 13 pages, 7 figures. Accepted for publication in A&

Effect of an ACTH(4-9) analogue on cisplatin neuropathy of longstanding duration: A phase II study

The efficacy of Org 2766, an ACTH(4–9) analogue, on the recovery of cisplatin neuropathy of longstanding duration was investigated in a phase II study. Twenty-two patients were treated with Org 2766 during a period of 4 months and vibration perception threshold (VPT) and sum scores for neuropathic symptoms and signs were compared with pre-treatment values. No change in VPT could be detected. Although there was a small improvement of clinical measures for neuropathy, no clear evidence for repair could be obtained. These results indicate no beneficial effect of Org 2766 on recovery of a longstanding cisplatin neuropathy

A 2.78 mm2 65 nm CMOS Gigabit MIMO Iterative Detection and Decoding Receiver

Iterative detection and decoding (IDD), combined with spatial-multiplexing multiple-input multiple-output (MIMO) transmission, is a key technique to improve spectral efficiency in wireless communications. In this paper we present the—to the best of our knowledge—first complete silicon implementation of a MIMO IDD receiver. MIMO detection is performed by a multi-core sphere decoder supporting up to 4×4 as antenna configuration and 64-QAM modulation. A flexible low-density parity check decoder is used for forward error correction. The 65 nm CMOS ASIC has a core area of 2.78 mm2 . Its maximum throughput exceeds 1 Gbit/s, at less than 1 nJ/bit. The MIMO IDD ASIC enables more than 2 dB performance gains with respect to non-iterative receivers