Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Characterizing the initial conditions of heavy-ion collisions at the LHC with mean transverse momentum and anisotropic flow correlations

Correlations between mean transverse momentum and anisotropic flow coefficients or are measured as a function of centrality in Pb–Pb and Xe–Xe collisions at sqrt(sNN) = 5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pt], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTO initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTO based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTO initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pt] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark–gluon plasma recreated in relativistic heavy-ion collisions

Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of ${\rm ^{3}_{\Lambda}\rm H}$ in p-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is ${\rm d} N /{\rm d} y =[\mathrm{6.3 \pm 1.8 (stat.) \pm 1.2 (syst.) ] \times 10^{-7}}$. The measurement is compared with the expectations of statistical hadronisation and coalescence models, which describe the nucleosynthesis in hadronic collisions. These two models predict very different yields of the hypertriton in small collision systems such as p-Pb and therefore the measurement of ${\rm d} N /{\rm d} y$ is crucial to distinguish between them. The precision of this measurement leads to the exclusion with a significance larger than 6$\sigma$ of some configurations of the statistical hadronisation, thus constraining the production mechanism of loosely bound states

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

General balance functions of identified charged hadron pairs of (pi,K,p) in Pb-Pb collisions at 2.76 TeV

First measurements of balance functions (BFs) of all combinations of identified charged hadron ( π , K, p) pairs in Pb–Pb collisions at √sNN = 2.76 TeV recorded by the ALICE detector are presented. The BF measurements are carried out as two-dimensional differential correlators versus the relative rapidity (delta-y) and azimuthal angle (delta-φ) of hadron pairs, and studied as a function of collision centrality. The delta-φ dependence of BFs is expected to be sensitive to the light quark diffusivity in the quark–gluon plasma. While the BF azimuthal widths of all pairs substantially decrease from peripheral to central collisions, the longitudinal widths exhibit mixed behaviors: BFs of π π and cross-species pairs narrow significantly in more central collisions, whereas those of KK and pp are found to be independent of collision centrality. This dichotomy is qualitatively consistent with the presence of strong radial flow effects and the existence of two stages of quark production in relativistic heavy-ion collisions. Finally, the first measurements of the collision centrality evolution of BF integrals are presented, with the observation that charge balancing fractions are nearly independent of collision centrality in Pb–Pb collisions. Overall, the results presented provide new and challenging constraints for theoretical models of hadron production and transport in relativistic heavy-ion collisions

K∗(892)0 and φ(1020) production in p-Pb collisions at √s NN = 8.16 TeV

The production of K*(892)(0) and phi(1020) resonances has been measured in p-Pb collisions at root s(NN) = 8.16 TeV using the ALICE detector. Resonances are reconstructed via their hadronic decay channels in the rapidity interval -0.5 8 GeV/c), the R-pPb values of all hadrons are consistent with unity within uncertainties. The R-pPb of K*(892)(0) and phi(1020) at root s(NN) = 8.16 and 5.02 TeV show no significant energy dependence

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

Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at root s = 13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (p(T)) of 0.2 GeV/c and up to p(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(T) range 0.5 < p(T) < 26 GeV/c at root s(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(T) dependence is observed in pp collisions, where the yield of high-p(T) electrons increases faster as a function of multiplicity than the one of low-p(T) electrons. The measurement in p-Pb collisions shows no p(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