Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Studies of anhydride-cured epoxy networks with bonded and unbonded polyhedral oligomeric silsesquioxane (POSS)

This work is focused on the effect of polyhedral oligomeric silsesquioxane (POSS) compounds bearing reactive and non-reactive groups on the properties of resultant epoxy-anhydride hybrids and the underlying mechanisms. With rapid developments in nanotechnology, there has been great interest in polymer nanocomposites such as epoxy-based hybrids. POSS compounds have been incorporated in amine-cured epoxies for property improvements. In contrast, POSS/epoxy hybrids based on anhydride cure agents are seldom studied due to challenges such as the kinetically-controlled cure process and the requirement of catalysts for effective curing which may lead to complex reaction kinetics. However, the benefits of longer pot lives, better controlled curing, higher thermal and dimensional stabilities may outweigh the detriments. Kinetics, morphological and thermal studies were carried out to elucidate the effect of a POSS-epoxy on the properties of an epoxy-anhydride system in which the epoxy has self-catalytic sites. The POSS tether length difference on the cure kinetics was investigated. Tailoring POSS tether chemistry to reduce the cure kinetics difference between resin components was also studied with a novel POSS-anhydride. Anhydride-cured epoxy hybrids containing POSS-imidazolium (POSS-IMC) surfactants and corresponding modified clays have been prepared. Their catalytic effects were examined with correlation to the resultant morphologies and impact on the thermal properties. Interfacial interactions of non-reactive POSS on the thermal properties of epoxy-anhydride hybrids have also been investigated with octa-phenyl POSS (OPS) and its brominated derivatives.DOCTOR OF PHILOSOPHY (MSE

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at √ s = 5.02 and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of √s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within 0.8pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|2GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at √s=13TeV.

Measurement of inclusive J/ψ\psi pair production cross section in pp collisions at s=13\sqrt{s} = 13 TeV

International audienceThe production cross section of inclusive J/$\psi$ pairs in pp collisions at a centre-of-mass energy $\sqrt{s} = 13$ TeV is measured with ALICE. The measurement is performed for J/$\psi$ in the rapidity interval $2.5 0$. The production cross section of inclusive J/$\psi$ pairs is reported to be $10.3 \pm 2.3 {\rm (stat.)} \pm 1.3 {\rm (syst.)}$ nb in this kinematic interval. The contribution from non-prompt J/$\psi$ (i.e. originated from beauty-hadron decays) to the inclusive sample is evaluated. The results are discussed and compared with data

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p−-Pb collisions

International audienceMeasurements of the production of electrons from heavy-flavour hadron decays in pp collisions at $\sqrt{s} = 13$ TeV at midrapidity with the ALICE detector are presented down to a transverse momentum ($p_{\rm T}$) of 0.2 GeV$/c$ and up to $p_{\rm T} = 35$ GeV$/c$, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p$-$Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the $p_{\rm T}$ range $0.5 < p_{\rm T} < 26$ GeV$/c$ at $\sqrt{s_{\rm NN}} = 8.16$ TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p$-$Pb collisions grow faster than linear with the self-normalised multiplicity. A strong $p_{\rm T}$ dependence is observed in pp collisions, where the yield of high-$p_{\rm T}$ electrons increases faster as a function of multiplicity than the one of low-$p_{\rm T}$ electrons. The measurement in p$-$Pb collisions shows no $p_{\rm T}$ dependence within uncertainties. The self-normalised yields in pp and p$-$Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

Observation of medium-induced yield enhancement and acoplanarity broadening of low-pTp_\mathrm{T} jets from measurements in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) hadron trigger in proton$-$proton and central Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb$-$Pb collisions. Recoil jet distributions are reported for jet resolution parameter $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,jet} < 140$ GeV$/c$ and trigger$-$recoil jet azimuthal separation $\pi/2 < \Delta\varphi < \pi$. The measurements exhibit a marked medium-induced jet yield enhancement at low $p_{\rm T}$ and at large azimuthal deviation from $\Delta\varphi\sim\pi$. The enhancement is characterized by its dependence on $\Delta\varphi$, which has a slope that differs from zero by 4.7$\sigma$. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation

Probing the Chiral Magnetic Wave with charge-dependent flow measurements in Pb-Pb collisions at the LHC

International audienceThe Chiral Magnetic Wave (CMW) phenomenon is essential to provide insights into the strong interaction in QCD, the properties of the quark-gluon plasma, and the topological characteristics of the early universe, offering a deeper understanding of fundamental physics in high-energy collisions. Measurements of the charge-dependent anisotropic flow coefficients are studied in Pb-Pb collisions at center-of-mass energy per nucleon-nucleon collision $\sqrt{s_{\mathrm{NN}}}=$ 5.02 TeV to probe the CMW. In particular, the slope of the normalized difference in elliptic ($v_{2}$) and triangular ($v_{3}$) flow coefficients of positively and negatively charged particles as a function of their event-wise normalized number difference, is reported for inclusive and identified particles. The slope $r_{3}^{\rm Norm}$ is found to be larger than zero and to have a magnitude similar to $r_{2}^{\rm Norm}$, thus pointing to a large background contribution for these measurements. Furthermore, $r_{2}^{\rm Norm}$ can be described by a blast wave model calculation that incorporates local charge conservation. In addition, using the event shape engineering technique yields a fraction of CMW ($f_{\rm CMW}$) contribution to this measurement which is compatible with zero. This measurement provides the very first upper limit for $f_{\rm CMW}$, and in the 10-60% centrality interval it is found to be 26% (38%) at 95% (99.7%) confidence level

Jet fragmentation transverse momentum distributions in pp and p-Pb collisions at s \sqrt{s} , sNN \sqrt{s_{\mathrm{NN}}} = 5.02 TeV

Jet fragmentation transverse momentum (j$_{T}$) distributions are measured in proton-proton (pp) and proton-lead (p-Pb) collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV with the ALICE experiment at the LHC. Jets are reconstructed with the ALICE tracking detectors and electromagnetic calorimeter using the anti-k$_{T}$ algorithm with resolution parameter R = 0.4 in the pseudorapidity range |η| < 0.25. The j$_{T}$ values are calculated for charged particles inside a fixed cone with a radius R = 0.4 around the reconstructed jet axis. The measured j$_{T}$ distributions are compared with a variety of parton-shower models. Herwig and Pythia 8 based models describe the data well for the higher j$_{T}$ region, while they underestimate the lower j$_{T}$ region. The j$_{T}$ distributions are further characterised by fitting them with a function composed of an inverse gamma function for higher j$_{T}$ values (called the “wide component”), related to the perturbative component of the fragmentation process, and with a Gaussian for lower j$_{T}$ values (called the “narrow component”), predominantly connected to the hadronisation process. The width of the Gaussian has only a weak dependence on jet transverse momentum, while that of the inverse gamma function increases with increasing jet transverse momentum. For the narrow component, the measured trends are successfully described by all models except for Herwig. For the wide component, Herwig and PYTHIA 8 based models slightly underestimate the data for the higher jet transverse momentum region. These measurements set constraints on models of jet fragmentation and hadronisation

Charged-particle production as a function of the relative transverse activity classifier in pp, p−-Pb, and Pb−-Pb collisions at the LHC

International audienceMeasurements of charged-particle production in pp, p$-$Pb, and Pb$-$Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum ($p_{\mathrm{T}}^{\rm trig}$) in the range $8<p_{\mathrm{T}}^{\rm trig}<15$ GeV$/c$. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, $R_{\mathrm{T}}=N_{\mathrm{ch}}^{\mathrm{T}}/\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$, is used to group events according to their UE activity, where $N_{\mathrm{ch}}^{\mathrm{T}}$ is the charged-particle multiplicity per event in the transverse region and $\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$ is the mean value over the whole analysed sample. The energy dependence of the $R_{\mathrm{T}}$ distributions in pp collisions at $\sqrt{s}=2.76$, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle $p_{\rm T}$ spectra as a function of $R_{\mathrm{T}}$ in the three azimuthal regions in pp, p$-$Pb, and Pb$-$Pb collisions at $\sqrt{s_{\rm NN}}=5.02$ TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p$-$Pb)