•Methods for meta-analysis of studies with individual participant data and continuous exposure variables are well described in the statistical literature but are not widely used in clinical and ...epidemiological research.•The purpose of this paper is to make the methods more accessible.•In a two-stage process, response curves for each study are estimated separately and then pointwise weighted averages are calculated using fixed effects or random effects methods.•A sample data set, segments of Stata and R code, and outputs are provided to enable replication and facilitate adaptation to other settings.
Methods for meta-analysis of studies with individual participant data and continuous exposure variables are well described in the statistical literature but are not widely used in clinical and epidemiological research. The purpose of this case study is to make the methods more accessible.
A two-stage process is demonstrated. Response curves are estimated separately for each study using fractional polynomials. The study-specific curves are then averaged pointwise over all studies at each value of the exposure. The averaging can be implemented using fixed effects or random effects methods.
The methodology is illustrated using samples of real data with continuous outcome and exposure data and several covariates. The sample data set, segments of Stata and R code, and outputs are provided to enable replication of the results.
These methods and tools can be adapted to other situations, including for time-to-event or categorical outcomes, different ways of modelling exposure-outcome curves, and different strategies for covariate adjustment.
A search for an exotic decay of the Higgs boson to a Z boson and a light pseudoscalar particle (a), decaying to a pair of leptons and a pair of photons, respectively, is presented. The search is ...based on proton-proton collision data at a center-of-mass energy of $\sqrt{s}$ = 13 TeV, collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 138 fb-1. The analysis probes pseudoscalar masses ma between 1 and 30 GeV, leading to two pairs of well-isolated leptons and photons. Upper limits at 95% confidence level are set on the Higgs boson production cross section times its branching fraction to two leptons and two photons. The observed (expected) limits are in the range of 1.1–17.8 (1.7–17.9) fb within the probed ma interval. An excess of data above the expected standard model background with a local (global) significance of 2.6 (1.3) standard deviations is observed for a mass hypothesis of ma = 3GeV. Limits on models involving axion-like particles, formulated as an effective field theory, are also reported.
A search for
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final state is presented, where H is the standard model (SM) Higgs boson. The search uses an event sample of proton-proton collisions corresponding to an integrated luminosity of 133
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with the CMS detector at the CERN LHC. The analysis introduces several novel techniques for deriving and validating a multi-dimensional background model based on control samples in data. A multiclass multivariate classifier customized for the
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final state is developed to derive the background model and extract the signal. The data are found to be consistent, within uncertainties, with the SM predictions. The observed (expected) upper limits at 95% confidence level are found to be 3.8 (3.8) and 5.0 (2.9) times the SM prediction for the
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An investigation was carried out to determine whether there were significant changes in nutrient intake over 17 years of adult life. The Medical Research Council National Survey of Health and ...Development is a longitudinal study of a nationally representative cohort of singleton births in the UK in 1946. Of this cohort, 1253 survey members provided information on diet recorded in a 5 d diary at age 36 years in 1982, 43 years in 1989 and 53 years in 1999. The outcome measures were mean intakes of energy, macronutrients, minerals and vitamins. There were significant changes in the intake of most nutrients in 1999 compared with previous years. Intakes of fat, Na, Fe and Cu have fallen, but there was a rising trend in the intakes of Ca, P, carotene, thiamin, pyridoxine, folic acid and vitamins C, D and E in both men and women. Additionally, intakes of K, Mg and vitamin K1 have risen in women. There were significant gender differences, women showing a higher percentage rise in the intakes of carotene, riboflavin, folic acid, vitamin C and vitamin E. These changes were related to changes in the consumption of certain key foods, such as the increased consumption of fruit and vegetables and a shift away from whole milk, butter and red meat. Most of these trends are in line with accepted nutritional guidelines. How far these changes are due to consumer choice and real changes in food composition or are due to artefacts inherent in the methodology is discussed.
A search is presented for a third-generation leptoquark (LQ) coupled exclusively to a τ lepton and a b quark. The search is based on proton-proton collision data at a center-of-mass energy of 13 TeV ...recorded with the CMS detector, corresponding to an integrated luminosity of 138 fb-1. Events with τ leptons and a varying number of jets originating from b quarks are considered, targeting the single and pair production of LQs, as well as nonresonant t-channel LQ exchange. An excess is observed in the data with respect to the background expectation in the combined analysis of all search regions. For a benchmark LQ mass of 2 TeV and an LQ-b-τ coupling strength of 2.5, the excess reaches a local significance of up to 2.8 standard deviations. Upper limits at the 95% confidence level are placed on the LQ production cross section in the LQ mass range 0.5–2.3 TeV, and up to 3 TeV for t-channel LQ exchange. Leptoquarks are excluded below masses of 1.22–1.88 TeV for different LQ models and varying coupling strengths up to 2.5. The study of nonresonant ττ production through t-channel LQ exchange allows lower limits on the LQ mass of up to 2.3 TeV to be obtained.
A measurement is presented of the primary Lund jet plane (LJP) density in inclusive jet production in proton-proton collisions. The analysis uses 138 fb-1 of data collected by the CMS experiment at ...$\sqrt{s}$ = 13 TeV. The LJP, a representation of the phase space of emissions inside jets, is constructed using iterative jet declustering. The transverse momentum kT and the splitting angle ΔR of an emission relative to its emitter are measured at each step of the jet declustering process. The average density of emissions as function of ln(kT/GeV) and ln(R/ΔR) is measured for jets with distance parameters R = 0.4 or 0.8, transverse momentum pT > 700 GeV, and rapidity |y| < 1.7. The jet substructure is measured using the charged-particle tracks of the jet. The measured distributions, unfolded to the level of stable charged particles, are compared with theoretical predictions from simulations and with perturbative quantum chromodynamics calculations. Due to the ability of the LJP to factorize physical effects, these measurements can be used to improve different aspects of the physics modeling in event generators.
Measurements are presented of the $B_s^0$ → μ+μ- branching fraction and effective lifetime, as well as results of a search for the B0 → μ+μ- decay in proton-proton collisions at at the LHC. The ...analysis is based on data collected with the CMS detector in 2016–2018 corresponding to an integrated luminosity of 140 fb-1. The branching fraction of the $B_s^0$ → μ+μ- decay and the effective $B_s^0$ meson lifetime are the most precise single measurements to date. No evidence for the B0 → μ+μ- decay has been found. All results are found to be consistent with the standard model predictions and previous measurements.
Positive allosteric modulators targeting the Y4 receptor (Y4R), a G protein-coupled receptor (GPCR) involved in the regulation of satiety, offer great potential in anti-obesity research. In this ...study, we selected 603 compounds by using quantitative structure–activity relationship (QSAR) models and tested them in high-throughput screening (HTS). Here, the novel positive allosteric modulator (PAM) VU0506013 was identified, which exhibits nanomolar affinity and pronounced selectivity toward the Y4R in engineered cell lines and mouse descending colon mucosa natively expressing the Y4R. Based on this lead structure, we conducted a systematic SAR study in two regions of the scaffold and presented a series of 27 analogues with modifications in the N- and C-terminal heterocycles of the molecule to obtain insight into functionally relevant positions. By mutagenesis and computational docking, we present a potential binding mode of VU0506013 in the transmembrane core of the Y4R. VU0506013 presents a promising scaffold for developing in vivo tools to move toward anti-obesity drug research focused on the Y4R.