Immunosuppressive Minimization Strategies in Kidney Transplantation

The long-term graft survival in renal transplantation results is still controversial, the toxicity and adverse reactions of the immunosuppressive drugs are implicated, as well as cellular and humoral antigen-specific immune mechanisms; therefore, different strategies for adapting immunosuppression are used to reduce the complications associated with the use of these drugs. Calcineurin inhibitors (CNI) require an adequate dose-dependent concentration leading to the appearance of drug-related adverse reactions. The variability in the required dose of CNI leads to minimization strategies that do not result in a higher acute rejection (AR) incidence when compared to other immunosuppressive agents. Early steroid withdrawal is another strategy, although with an increase in AR, but without an impact on the function and survival of the renal graft. The reduction of mycophenolate mofetil to 1.5 g/day seems to be a therapeutic option, decreasing the infectious, hematological and gastrointestinal adverse reactions. Finally, alemtuzumab, bortezomib, belatacept and cellular therapies are in the search for the new treatments, whose premise is the induction of donor-specific nonresponse in the context of operational tolerance or mixed chimerism. The use of adapted and adequate immunosuppression has led to variable results and some are very encouraging; however, they must be validated with experimental studies

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

Neutral pion and η\eta meson production in p-Pb collisions at sNN=5.02\sqrt{s_\mathrm{NN}} = 5.02 TeV

Neutral pion and $\eta$ meson invariant differential yields were measured in non-single diffractive p–Pb collisions at $\sqrt{s_{\mathrm{NN}}}$  = 5.02 TeV with the ALICE experiment at the CERN LHC. The analysis combines results from three complementary photon measurements, utilizing the PHOS and EMCal calorimeters and the Photon Conversion Method. The invariant differential yields of $\pi ^{0}$ and $\eta$ meson inclusive production are measured near mid-rapidity in a broad transverse momentum range of $0.3 4$\hbox {GeV}/c$at$0.483 \pm 0.015_{\mathrm{stat}} \pm 0.015_{\mathrm{sys}}$. A deviation from$m_{\mathrm{T}}$scaling is observed for$p_{\mathrm{T}}<$2$\hbox {GeV}/c$. The measured$\eta /\pi ^{0}$ratio is consistent with previous measurements from proton-nucleus and pp collisions over the full$p_{\mathrm{T}}$range. The measured$\eta /\pi ^{0}$ratio at high$p_{\mathrm{T}}$also agrees within uncertainties with measurements from nucleus–nucleus collisions. The$\pi ^{0}$and$\eta $yields in p–Pb relative to the scaled pp interpolated reference,$R_{{\mathrm{pPb}}}$, are presented for$0.3 < p_{\mathrm{T}}<$20$\hbox {GeV}/c$and$0.7 < p_{\mathrm{T}}<$20$\hbox {GeV}/c$, respectively. The results are compared with theoretical model calculations. The values of$R_{{\mathrm{pPb}}}$are consistent with unity for transverse momenta above 2$\hbox {GeV}/c$ . These results support the interpretation that the suppressed yield of neutral mesons measured in Pb–Pb collisions at LHC energies is due to parton energy loss in the hot QCD medium

Analysis of the apparent nuclear modification in peripheral Pb–Pb collisions at 5.02 TeV

International audienceCharged-particle spectra at midrapidity are measured in Pb–Pb collisions at the centre-of-mass energy per nucleon–nucleon pair sNN=5.02 TeV and presented in centrality classes ranging from most central (0–5%) to most peripheral (95–100%) collisions. Possible medium effects are quantified using the nuclear modification factor ( RAA ) by comparing the measured spectra with those from proton–proton collisions, scaled by the number of independent nucleon–nucleon collisions obtained from a Glauber model. At large transverse momenta ( 8<pT<20GeV/c ), the average RAA is found to increase from about 0.15 in 0–5% central to a maximum value of about 0.8 in 75–85% peripheral collisions, beyond which it falls off strongly to below 0.2 for the most peripheral collisions. Furthermore, RAA initially exhibits a positive slope as a function of pT in the 8–20 GeV/c interval, while for collisions beyond the 80% class the slope is negative. To reduce uncertainties related to event selection and normalization, we also provide the ratio of RAA in adjacent centrality intervals. Our results in peripheral collisions are consistent with a PYTHIA-based model without nuclear modification, demonstrating that biases caused by the event selection and collision geometry can lead to the apparent suppression in peripheral collisions. This explains the unintuitive observation that RAA is below unity in peripheral Pb–Pb, but equal to unity in minimum-bias p–Pb collisions despite similar charged-particle multiplicities

Anisotropic flow of identified particles in Pb-Pb collisions at sNN=5.02 {\sqrt{s}}_{\mathrm{NN}}=5.02 TeV

The elliptic (v$_{2}$), triangular (v$_{3}$), and quadrangular (v$_{4}$) flow coefficients of π$^{±}$, K$^{±}$, $\mathrm{p}+\overline{\mathrm{p}},\kern0.5em \Lambda +\overline{\Lambda},\kern0.5em {\mathrm{K}}_{\mathrm{S}}^0$ , and the ϕ-meson are measured in Pb-Pb collisions at ${\sqrt{s}}_{\mathrm{NN}}=5.02$ TeV. Results obtained with the scalar product method are reported for the rapidity range |y| < 0.5 as a function of transverse momentum, p$_{T}$, at different collision centrality intervals between 0–70%, including ultra-central (0–1%) collisions for π$^{±}$, K$^{±}$, and $\mathrm{p}+\overline{\mathrm{p}}$ . For p$_{T}$ < 3 GeV/c, the flow coefficients exhibit a particle mass dependence. At intermediate transverse momenta (3 < p$_{T}$ < 8–10 GeV/c), particles show an approximate grouping according to their type (i.e., mesons and baryons). The ϕ-meson v$_{2}$, which tests both particle mass dependence and type scaling, follows $\mathrm{p}+\overline{\mathrm{p}}$ v$_{2}$ at low p$_{T}$ and π$^{±}$ v$_{2}$ at intermediate p$_{T}$. The evolution of the shape of v$_{n}$(p$_{T}$) as a function of centrality and harmonic number n is studied for the various particle species. Flow coefficients of π$^{±}$, K$^{±}$, and $\mathrm{p}+\overline{\mathrm{p}}$ for p$_{T}$ < 3 GeV/c are compared to iEBE-VISHNU and MUSIC hydrodynamical calculations coupled to a hadronic cascade model (UrQMD). The iEBE-VISHNU calculations describe the results fairly well for p$_{T}$ < 2.5 GeV/c, while MUSIC calculations reproduce the measurements for p$_{T}$ < 1 GeV/c. A comparison to v$_{n}$ coefficients measured in Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}=2.76$ TeV is also provided

π0\pi ^{0} and η\eta meson production in proton-proton collisions at s=8\sqrt{s}=8 TeV

An invariant differential cross section measurement of inclusive $\pi ^{0}$ and $\eta$ meson production at mid-rapidity in pp collisions at $\sqrt{s}=8$  TeV was carried out by the ALICE experiment at the LHC. The spectra of $\pi ^{0}$ and $\eta$ mesons were measured in transverse momentum ranges of $0.33.5$   $\text{ GeV/c }$ . However, a deviation from this empirical scaling rule is observed for transverse momenta below $p_{ \text{ T }} <3.5$   $\text{ GeV/c }$ in the $\eta /\pi ^0$ ratio with a significance of $6.2\sigma$

Relative particle yield fluctuations in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

First results on K/$\pi$, p/$\pi$ and K/p fluctuations are obtained with the ALICE detector at the CERN LHC as a function of centrality in Pb-Pb collisions at $\sqrt{s_{\rm NN}}=2.76$ TeV. The observable $\nu_{\rm dyn}$, which is defined in terms of the moments of particle multiplicity distributions, is used to quantify the magnitude of dynamical fluctuations of relative particle yields and also provides insight into the correlation between particle pairs. This study is based on a novel experimental technique, called the Identity Method, which allows one to measure the moments of multiplicity distributions in case of incomplete particle identification. The results for p/$\pi$ show a change of sign in $\nu_{\rm dyn}$ from positive to negative towards more peripheral collisions. For central collisions, the results follow the smooth trend of the data at lower energies and $\nu_{\rm dyn}$ exhibits a change in sign for p/$\pi$ and K/p.First results on $\hbox {K}/\pi$ , $\hbox {p}/\pi$ and K/p fluctuations are obtained with the ALICE detector at the CERN LHC as a function of centrality in $\text{ Pb--Pb }$ collisions at $\sqrt{s_\mathrm{{NN}}} =2.76\hbox { TeV}$ . The observable $\nu _{\mathrm{dyn}}$ , which is defined in terms of the moments of particle multiplicity distributions, is used to quantify the magnitude of dynamical fluctuations of relative particle yields and also provides insight into the correlation between particle pairs. This study is based on a novel experimental technique, called the Identity Method, which allows one to measure the moments of multiplicity distributions in case of incomplete particle identification. The results for $\hbox {p}/\pi$ show a change of sign in $\nu _{\mathrm{dyn}}$ from positive to negative towards more peripheral collisions. For central collisions, the results follow the smooth trend of the data at lower energies and $\nu _{\mathrm{dyn}}$ exhibits a change in sign for $\hbox {p}/\pi$ and K/p

Suppression of Λ(1520) resonance production in central Pb–Pb collisions at √sNN = 2.76 TeV

The production yield of the Λ(1520) baryon resonance is measured at mid-rapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the LHC. The measurement is performed in the Λ(1520)→pK− (and charge conjugate) hadronic decay channel as a function of the transverse momentum (pT) and collision centrality. The pT-integrated production rate of Λ(1520) relative to Λ in central collisions is suppressed by about a factor of 2 with respect to peripheral collisions. This is the first observation of the suppression of a baryonic resonance at the LHC and the first 3σ evidence of Λ(1520) suppression within a single collision system. The measured Λ(1520)/Λ ratio in central collisions is smaller than the value predicted by the statistical hadronisation model calculations. The shape of the measured pT distribution and the centrality dependence of the suppression are reproduced by the EPOS3 Monte Carlo event generator. The measurement adds further support to the formation of a dense hadronic phase in the final stages of the evolution of the fireball created in heavy-ion collisions, lasting long enough to cause a significant reduction in the observable yield of short-lived resonances