Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates

From Romantic Gothic to Victorian Medievalism: 1817 and 1877

"The Cambridge History of the Gothic was conceived in 2015, when Linda Bree, then Editorial Director at Cambridge University Press, first suggested the idea to us

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Epitaxial InGaAs source/drain regions for highly scaled nMOS devices

Paper presented at the Intel Ireland Research Conference, which took place in Clontarf Castle (Dublin, Ireland) during 21-23th November 2013.Molecular Beam Epitaxy of highly-doped InGaAs:Si ultra shallow junctions (USJ) and selective growth of self-aligned InGaAs source/drain (S/D) extended regions aimed at high performance logic beyond the 10nm CMOS technology node are investigated. Silicon volume-doping, single ¿-doping and multiple (pulsed) ¿-doping of InGaAs USJ have been studied as a function of growth temperature, V:III flux ratio and Si flux by ToF-SIMS profiling, AFM, FTIR and HR-TEM. Defect-free USJ with narrow ¿-Si distributions and peak concentrations up to 1x1020cm-3 are demonstrated. 1 Highly doped InGaAs:Si ultra-shallow junctions. A strong need exists to develop III-V n-type doping strategies that are capable of delivering low resistivity and low-defect ultra shallow source/drain regions with dopant concentrations above 1019 cm-3 and junction depths of 5-10nm. In this work, 5-8 nm thick InGaAs USJ with Si peak concentrations between 1x1019cm-3 and 1.5x1020cm-3 have been grown, with the highest values corresponding to triple Si ¿-layers. Indium segregation to the surface occurs for all growth temperatures studied (375-430ºC). AFM imaging and HR-TEM indicate an improvement in the crystal quality of the InGaAs USJs for substrate temperatures above 400ºC, due to a transition from a multi-layer to a layer-by-layer growth mode. A self-organised pattern is observed up to Si concentrations of ca. 1×1020cm-3. Above this value, Si segregation to the surface occurs, increasing the surface roughness and degrading the crystal quality of the InGaAs USJs. 2 Raised S/D InGaAs extended regions. In ultimately scaled devices the use of raised S/D structures will be essencial to reduce the contact series resistance without affecting short channel effects, e.g. DIBL. Optimization of the MBE process has allowed us to achieve high selectivity and absence of microtrench formation between the regrown S/D regions and the patterned HfO2 gate oxide, as shown in Figure 2

Surface self-organization and structure of highly doped n-InGaAs ultra-shallow junctions

Paper presented at 5th International Conference on Defects Recognition, Imaging and Physics in Semiconductors that took place in Warsaw (Poland) during 15-19th September 2013.Compound semiconductors having high electron mobility and high injection velocity such as InGaAs are being profusely studied as possible candidates to replace Si as the channel material in highly scaled MOSFETs. One of the most critical challenges of III-V MOSFET miniaturisation lies in achieving low resistance source/drain access regions suitable for high performance logic beyond the 10nm technology node. A strong need exists to develop III-V n-type doping strategies that are capable of delivering low resistivity and low-defect ultra shallow source/drain regions with dopant concentrations above 1019 cm-3 and junction depths of Xj=5-10nm for future devices. In this work we study the Si doping characteristics of MBE grown InxGa1-xAs (x=0.17-0.33) ultra-shallow junctions (Xj¿8nm) deposited on GaAs(001) substrates under different substrate and Si effusion cell temperatures and V:III flux ratios. To this aim three in-situ doping strategies have been explored, namely homogeneous co-deposition, continuous ¿-doping and pulsed ¿-doping. The resulting Si-doping levels , determined by time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis, were found to lie between 2.7x1018cm-3 and 5.8x1019cm-3, the highest values corresponding to InGaAs junctions with triple Si ¿-layers. Elemental profiles evidence In segregation to the surface even in those samples grown at the lowest substrate temperature studied (375ºC), for which the highest Si solubility is observed. Atomic force microscopy (AFM) imaging and high-resolution transmission electron microscopy (HR-TEM) indicate an improvement in the crystal quality of the InGaAs USJs for growth temperatures above 400ºC. A characteristic self-organization of the surface into a cross hatch pattern is observed up to Si concentrations of ca. 3×1019cm-3. Above this value the InGaAs crystalline quality is degraded and the surface roughness increases significantly.Financial support under grant MAT2011-22536 is greatly acknowledged.Peer Reviewe

A putative gnetalean gymnosperm Cariria orbiculiconiformis gen. nov et spec. nov from the Early Cretaceous of northern Gondwana

Cariria orbiculiconiformis gen. nov. et spec. nov., a gymnosperm with gnetoid characters is described from the upper Aptian Crato Formation of the Araripe Basin in northeastern Brazil. Gross-morphology and anatomical details have been studied and characters have been discussed in respect to various seed plants. Several of these characters fit best with those of Gnetales and their putative fossil allies. However, the fossil plant cannot be assigned to any known extinct or extant group of seed plants in their current circumscription. Stem gross-morphology, xylotomical characters and epidermal features indicate a gnetophytic relationship, whereas characters of the reproductive organs are rather distinct from those found in extant taxa. The reproductive unit of the new taxon represents a triple organ consisting of two dichasial ovulate structures and one median pollen-producing structure containing smooth, monosulcate, boat-shaped pollen in-situ. Each ovulate structure consists of two distinct pairs of bracts, a sterile one at the base and a fertile one forming a terminal orbicular capsule. Stiff processes found in the apex of the ovulate structure may represent micropylar tubes of seeds, as seen in the Bennettitales-Erdtmanithecales-Gnetales group. C orbiculiconiformis gen. nov. et spec. nov. was ans herbaceous or semi-shrub-like plant that may have been adapted to the r-strategy in a stressful environment. (C) 2011 Elsevier B.V. All rights reserved