Collaborative modeling of the benefits and harms associated with different U.S. Breast cancer screening strategies

Background: Controversy persists about optimal mammography screening strategies. Objective: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. Design: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. Setting: United States. Patients: Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. Intervention: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. Measurements: Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and qualityadjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. Results: Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar bene-fits, but more harms than other strategies). For groups with a 2-to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. Limitation: Other imaging technologies, polygenic risk, and nonadherence were not considered. Conclusion: Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening

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

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb–Pb collisions at √sNN = 2.76 TeV

Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp, peripheral (60–80%) and central (0–5%) Pb–Pb collisions at √sNN = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT ≈ 3 GeV/c in central Pb–Pb collisions. Below the peak, pT 10 GeV/c particle ratios in pp and Pb–Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets

Multiplicity dependence of jet-like two-particle correlation structures in p–Pb collisions at √sNN=5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 < pT,assoc < pT,trig < 5.0 GeV/c is examined, to include correlations induced by jets originating from low momentum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |η| < 0.9. The near-side long-range pseudorapidity correlations observed in high-multiplicity p–Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton–parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p–Pb collisions. Further, the number scales only in the intermediate multiplicity region with the number of binary nucleon–nucleon collisions estimated with a Glauber Monte-Carlo simulation

Beauty production in pp collisions at √s=2.76 TeV measured via semi-electronic decays

The ALICE Collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y| < 0.8 and transverse momentum 1 < pT < 10 GeV/c, in pp collisions at √s = 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD predictions agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e = 3.47 ± 0.40(stat) +1.12 −1.33(sys) ± 0.07(norm) μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) calculations to obtain the total bb production ¯ cross section, σbb¯ = 130 ± 15.1(stat) +42.1 −49.8(sys) +3.4 −3.1(extr) ± 2.5(norm) ± 4.4(BR) μb

Dielectron and heavy-quark production in inelastic and high-multiplicity proton–proton collisions at √s = 13 TeV

The measurement of dielectron production is presented as a function of invariant mass and transverse momentum (pT) at midrapidity (|ye| < 0.8) in proton–proton (pp) collisions at a centre-of-mass energy of √s = 13 TeV. The contributions from light-hadron decays are calculated from their measured cross sections in pp collisions at √s = 7 TeV or 13 TeV. The remaining continuum stems from correlated semileptonic decays of heavy-flavour hadrons. Fitting the data with templates from two different MC event generators, PYTHIA and POWHEG, the charm and beauty cross sections at midrapidity are extracted for the first time at this collision energy: dσcc¯/dy|y=0 = 974 ± 138 (stat.) ± 140 (syst.) ± 214(BR) μb and dσbb¯ /dy|y=0 = 79 ± 14 (stat.) ± 11 (syst.) ± 5(BR) μb using PYTHIA simulations and dσcc¯/dy|y=0 = 1417 ± 184 (stat.) ± 204 (syst.) ± 312(BR) μb and dσbb¯ /dy|y=0 = 48 ± 14 (stat.) ± 7 (syst.) ± 3(BR) μb for POWHEG. These values, whose uncertainties are fully correlated between the two generators, are consistent with extrapolations from lower energies. The different results obtained with POWHEG and PYTHIA imply different kinematic correlations of the heavy-quark pairs in these two generators. Furthermore, comparisons of dielectron spectra in inelastic events and in events collected with a trigger on high charged-particle multiplicities are presented in various pT intervals. The differences are consistent with the already measured scaling of light-hadron and open-charm production at high charged-particle multiplicity as a function of pT. Upper limits for the contribution of virtual direct photons are extracted at 90% confidence level and found to be in agreement with pQCD calculations