Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience.

BACKGROUND/AIMS: We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. METHODS: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. RESULTS: Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). CONCLUSION: Safety and effectiveness data on use of rhIGF-1 in a 'real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: Results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE

Background: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Objectives: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). Patients/Methods: All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). Results: In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Conclusions: Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles. \ua9 2012 International Society on Thrombosis and Haemostasis

Centrality dependence of \u3c0, K, and p production in Pb-Pb collisions at sqrt[s_{NN}]=2.76 TeV

In this paper measurements are presented of \u3c0\ub1, K\ub1, p, and p(bar) production at midrapidity (|y| < 0.5), in Pb-Pb collisions at 1asNN= 2.76 TeV as a function of centrality. The measurement covers the transverse-momentum (pT ) range from 100, 200, and 300 MeV/c up to 3, 3, and 4.6 GeV/c for \u3c0, K, and p, respectively. The measured pT distributions and yields are compared to expectations based on hydrodynamic, thermal and recombination models. The spectral shapes of central collisions show a stronger radial flow than measured at lower energies, which can be described in hydrodynamic models. In peripheral collisions, the pT distributions are not well reproduced by hydrodynamic models. Ratios of integrated particle yields are found to be nearly independent of centrality. The yield of protons normalized to pions is a factor 3c1.5 lower than the expectation from thermal models

Long-range angular correlationsof \u3c0, K and p in p\u2013Pb collisions at 1asNN =5.02TeV

Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3<pT<4 GeV/c. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |\u3b7lab|<0.8. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of pT and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, v2p, is observed to be smaller than that for pions, v2\u3c0, up to about pT=2 GeV/c. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The v2p is found to be smaller at low pT and larger at higher pT than v2\u3c0, with a crossing occurring at about 2 GeV/c. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system

J/\u3c8 Elliptic Flow in Pb-Pb Collisions at sqrt[s_{NN}]=2.76\u2009\u2009TeV

We report on the first measurement of inclusive J/\u3c8 elliptic flow v2 in heavy-ion collisions at the LHC. The measurement is performed with the ALICE detector in Pb-Pb collisions at 1asNN=2.76 TeV in the rapidity range 2,5<y<4,0. The dependence of the J=c v2 on the collision centrality and on the J/\u3c8 transverse momentum is studied in the range 0 64pT 64 10 GeV/c. For semicentral Pb-Pb collisions at 1asNN=2.76 TeV, an indication of nonzero v2 is observed with a largest measured value of v2=0.116 \ub1 0.046 (stat) \ub1 0:029 (syst) for J/\u3c8 in the transverse momentum range 2 64 pT 64 4 GeV/c. The elliptic flow measurement complements the previously reported ALICE results on the inclusive J/\u3c8 nuclear modification factor and favors the scenario of a significant fraction of J/\u3c8 production from charm quarks in a deconfined partonic phase

Relationship between the mineralogical composition of the clay fraction of some andalusian caracteristic soils and theri behaviour in relation to potassium

12 páginas, 7 figuras, 3 tablas, 7 referencias.[ES]: Se estudia la fracción arcilla de los suelos más característicos de nuestra región y su comportamiento frente al potasio, relacionándolo con la composición mineralógica de dicha fracción. Exceptuando el suelo fersialítico, los diferentes horizontes de cada suelo no presentan variaciones importantes en su comportamiento frente al potasio. Los suelos vérticos litomorfos y vérticos topomorfos presentan los valores más altos de Kx, lo que está de acuerdo con una mayor edafización y con altas concentraciones de montmorillonita e ilita. El suelo calcimorfo, a pesar de poseer composición mineralógica simlar, está muy poco evolucionado y presenta valores más bajos de Kx, similares a los del suelo aluvial, que está asimismo poco evolucionado, con alta proporción de ilita, a la que acompañan pequeñas proporciones de montmorillonita y caolinita. En el suelo fersialítico lavado disminuye el valor de Kx, al descender en el perfil, en el mismo sentido en que disminuye la ilita y aumenta la montmorillonita. Los horizontes C de los suelos de gran desarrollo edafogenético presentan en relación con los horizontes superiores, a pesar de poseer composición mineralógica similar, valores muy pequeños de Kx. El grado de desarrollo del suelo es el que tiene mayor influencia en los valores de Kx. Los tratamientos de eliminación de materia orgánica y/o geles producen un aumento muy apreciable de los valores de Kx.[EN]: The clay fractions of soils caracteristic of western Anclalucía and their behaviour in relation to potassium are studied, and the latter in related to the mineralogical composition of the former. Except the "fersialitico soil" (Rhocloxeralfs), the various horizons of each soil do not present distinct variations in their behaviour in relation to potassium. The "vertisol litomorfo" (chromoxererts) and «topomorfo» (Pelloxererts) soils present the highest values of Kx which agrees with the strong weathering of these soils and their nigh proportions of montmoillonite and illite. The "calcimorfo soil" (Calciorthids) is little weathered and present lower values of Kx, despite its mineralogical composition, which is analogous to the preceding soils. Similarly low values of Kx are obtained for the «aluvial soil» (Xerofluvents), also little weathered, which contains high proportion of illite, with small amounts of montmorillonite and kaolinite. The value of Kx and the proportion of illite for the leached fersialitico soil decrease and the proportion of montmorillonite increases as getting down across the profile. C horizons of soils with high podogenic development present much lower values of Kx than upper horizona, despite the analogy of their mineralogical compositions. The degree of development of soils has the highest influence on Kx, values. Treatments for removing organic matter and/or gels originate important increases in Kx values.Peer reviewe

Measurement of charm production at central rapidity in proton-proton collisions at 1as = 2.76 TeV

The p t-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D0, D+, and D*+ in the rapidity range |y| &lt; 0.5, and for transverse momentum 1 &lt; p t &lt; 12 GeV/c, were measured in proton-proton collisions at 1as = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D 0 \u2192 K -\u3c0 +, D + \u2192 K -\u3c0 +\u3c0 +, D *+ \u2192 D 0\u3c0 +, and their charge conjugates, and was performed on a L int = 1.1 nb -1 event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at 1as = 2.76 TeV and at 7 TeV was evaluated by extrapolating to the full phase space the p t-differential production cross sections at 1as = 2.76 TeV and our previous measurements at 1as = 7 TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cd D mesons produced in a vector state was also determined. \ua9 2012 SISSA