The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality

Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally. On the basis of these data, we present ten actionable recommendations, half of which are oriented towards health-care providers and half of which focus primarily on health policy. A fundamental shift must occur, in which health promotion, prevention, proactive casefinding, early identification of progressive liver fibrosis, and early treatment of liver diseases replace the current emphasis on the management of end-stage liver disease complications. A considerable focus should be put on underserved and marginalised communities, including early diagnosis and management in children, and we provide proposals on how to better target disadvantaged communities through health promotion, prevention, and care using multilevel interventions acting on current barriers. Underlying this transformative shift is the need to enhance awareness of the preventable and treatable nature of many liver diseases. Therapeutic nihilism, which is prevalent in current clinical practice across a range of medical specialities as well as in many patients themselves, has to end. We wish to challenge medical specialty protectionism and invite a broad range of stakeholders, including primary care physicians, nurses, patients, peers, and members of relevant communities, along with medical specialists trained in obesity, diabetes, liver disease, oncology, cardiovascular disease, public health, addictions, infectious diseases, and more, to engage in integrated person-centred liver patient care across classical medical specialty boundaries. This shift includes a revision in how we converse about liver disease and speak with our patients, and a reappraisal of disease-related medical nomenclature conducted to increase awareness and reduce the social stigmatisation associated with liver disease. Reimbursement mechanisms and insurance systems must be harmonised to account for patient-centric, multimorbidity models of care across a range of medical specialties, and the World Health Assembly resolution to improve the transparency and fairness of market prices for medicines throughout Europe should be reinforced. Finally, we outline how Europe can move forward with implementation of effective policy action on taxation, food reformulation, and product labelling, advertising, and availability, similar to that implemented for tobacco, to reduce consumption of alcohol, ultraprocessed foods, and foods with added sugar, especially among young people. We should utilise the window of opportunity created by the COVID-19 pandemic to overcome fragmentation and the variability of health prevention policies and research across Europe. We argue that the liver is a window to the 21st-century health of the European population. Through our proposed syndemic approach to liver disease and social and health inequities in Europe, the liver will serve as a sentinel for improving the overall health of European populations

Transverse momentum and pseudorapidity distributions of charged hadrons in pp collisions at (s)\sqrt(s) = 0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at sqrt(s) = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(charged)/d(eta) for |eta| < 0.5, are 3.48 +/- 0.02 (stat.) +/- 0.13 (syst.) and 4.47 +/- 0.04 (stat.) +/- 0.16 (syst.), respectively. The results at 0.9 TeV are in agreement with previous measurements and confirm the expectation of near equal hadron production in p-pbar and pp collisions. The results at 2.36 TeV represent the highest-energy measurements at a particle collider to date

Measurement of the charge ratio of atmospheric muons with the CMS detector

We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/ c to 1 TeV/ c . The surface flux ratio is measured to be 1.2766±0.0032(stat.)±0.0032(syst.) , independent of the muon momentum, below 100 GeV/ c . This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments.We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 \pm 0.0032(stat.) \pm 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments

Transverse-momentum and pseudorapidity distributions of charged hadrons in pppp collisions at s\sqrt{s} = 7 TeV

Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at $\sqrt{s} = 7$~TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity \dnchdeta|_{|\eta| < 0.5} = 5.78\pm 0.01\stat\pm 0.23\syst for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from $\sqrt{s} = 0.9$ to 7~TeV is 66.1\%\pm 1.0\%\stat\pm 4.2\%\syst. The mean transverse momentum is measured to be 0.545\pm 0.005\stat\pm 0.015\syst\GeVc. The results are compared with similar measurements at lower energies.Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at sqrt(s) = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity, dN(charged)/d(eta), for |eta| < 0.5, of 5.78 +/- 0.01 (stat) +/- 0.23 (syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from sqrt(s) = 0.9 to 7 TeV is 66.1% +/- 1.0% (stat) +/- 4.2% (syst). The mean transverse momentum is measured to be 0.545 +/- 0.005 (stat) +/- 0.015 (syst) GeV/c. The results are compared with similar measurements at lower energies

J Exp Med

To investigate the role of Lyt-2 and Thy-1 in cytolysis, we have generated, by ethyl methanesulfonate mutagenesis and selection, variants of the cloned cytolytic T lymphocyte line L3 that specifically lack either Lyt-2 or Thy-1. An analysis of these variants indicates that neither Lyt-2 nor Lyt-3 is responsible for the lethal hit, but suggests that Lyt-2 and/or Lyt-3 are required for an antigen receptor functional in cytolysis. The data also suggest that the expression of Lyt-3 on the cell surface is not independent of the expression of Lyt-2. Finally the data indicate the Thy-1 plays no role in cytolysis.6788878PMC218609