Postmortem metabolomics: strategies to assess time-dependent postmortem changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

Postmortem redistribution (PMR) can result in artificial drug concentration changes following death and complicate forensic case interpretation. Currently, no accurate methods for PMR prediction exist. Hence, alternative strategies were developed investigating the time-dependent postmortem behavior of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram. For 477 authentic postmortem cases, femoral blood samples were collected at two postmortem time-points. All samples were quantified for drugs of abuse (targeted; liquid chromatography-tandem mass spectrometry LC-MS/MS) and characterized for small endogenous molecules (untargeted; gas chromatography-high resolution MS (GC-HRMS). Trends for significant time-dependent concentration decreases (diazepam (n = 137), nordiazepam (n = 126)), increases (mirtazapine (n = 55), citalopram (n = 50)) or minimal median postmortem changes (morphine (n = 122), codeine (n = 92)) could be observed. Robust mathematical mixed effect models were created for the generalized postmortem behavior of diazepam and nordiazepam, which could be used to back-calculate drug concentrations towards a time-point closer to the estimated time of death (caution: inter-individual variability). Significant correlations between time-dependent concentration changes of morphine, mirtazapine and citalopram with individual endogenous molecules could be determined; no correlation was deemed strong enough for successful a posteriori estimation on the occurrence of PMR for specific cases. The current dataset did successfully lead to a significant knowledge gain in further understanding the time-dependent postmortem behavior of the studied drugs (of abuse)

Postmortem Metabolomics: Strategies to Assess Time-Dependent Postmortem Changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

Postmortem redistribution (PMR) can result in artificial drug concentration changes following death and complicate forensic case interpretation. Currently, no accurate methods for PMR prediction exist. Hence, alternative strategies were developed investigating the time-dependent postmortem behavior of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram. For 477 authentic postmortem cases, femoral blood samples were collected at two postmortem time-points. All samples were quantified for drugs of abuse (targeted; liquid chromatography-tandem mass spectrometry LC-MS/MS) and characterized for small endogenous molecules (untargeted; gas chromatography-high resolution MS (GC-HRMS). Trends for significant time-dependent concentration decreases (diazepam (n = 137), nordiazepam (n = 126)), increases (mirtazapine (n = 55), citalopram (n = 50)) or minimal median postmortem changes (morphine (n = 122), codeine (n = 92)) could be observed. Robust mathematical mixed effect models were created for the generalized postmortem behavior of diazepam and nordiazepam, which could be used to back-calculate drug concentrations towards a time-point closer to the estimated time of death (caution: inter-individual variability). Significant correlations between time-dependent concentration changes of morphine, mirtazapine and citalopram with individual endogenous molecules could be determined; no correlation was deemed strong enough for successful a posteriori estimation on the occurrence of PMR for specific cases. The current dataset did successfully lead to a significant knowledge gain in further understanding the time-dependent postmortem behavior of the studied drugs (of abuse)

Mathematical modelling of fibre-enhanced perfusion inside a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue-engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy's law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceMeasurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb$^{−1}$. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant $\textrm{t}\overline{\textrm{t}}$ background. A cross section of $79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right)$ pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext

Search for Higgs Boson and Observation of Z Boson through their Decay into a Charm Quark-Antiquark Pair in Boosted Topologies in Proton-Proton Collisions at s\sqrt{s} =13 TeV

A search for the standard model (SM) Higgs boson (H) produced with transverse momentum greater than 450 GeV and decaying to a charm quark-antiquark ($\mathrm{c\bar{c}}$) pair is presented. The search is performed using proton-proton collision data collected at $\sqrt{s}$ = 13 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb$^{-1}$. Boosted H $\to$$\mathrm{c\bar{c}}$ decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Z $\to$$\mathrm{c\bar{c}}$ decay process, which is observed in association with jets at high $p_\mathrm{T}$ for the first time with a signal strength of 1.00 $_{-0.14}^{+0.17}$ (syst) $\pm$ 0.08 (theo) $\pm$ 0.06 (stat), defined as the ratio of the observed process rate to the standard model expectation. The observed (expected) upper limit on $\sigma$(H) $\mathcal{B}$(H $\to$$\mathrm{c\bar{c}}$) is set at 47 (39) times the SM prediction at 95% confidence level

Search for pair production of vector-like quarks in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A search is presented for vector-like $\mathrm{T}$ and $\mathrm{B}$ quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for $\mathrm{T}$ quark masses up to 1.54 TeV and $\mathrm{B}$ quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T} \overline{\mathrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B} \overline{\mathrm{B}}$ production with $\mathrm{B}$ quark decays to tW.A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016–2018, with an integrated luminosity of 138 fb$^{−1}$. Events are separated into single-lepton, same-sign charge dilepton, and multi-lepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\textrm{T}\overline{\textrm{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\textrm{B}\overline{\textrm{B}}$ production with B quark decays to tW.[graphic not available: see fulltext]A search is presented for vector-like T and B quark-antiquark pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV. Data were collected by the CMS experiment at the CERN LHC in 2016-2018, with an integrated luminosity of 138 fb$^{-1}$. Events are separated into single-lepton, same-sign charge dilepton, and multilepton channels. In the analysis of the single-lepton channel a multilayer neural network and jet identification techniques are employed to select signal events, while the same-sign dilepton and multilepton channels rely on the high-energy signature of the signal to distinguish it from standard model backgrounds. The data are consistent with standard model background predictions, and the production of vector-like quark pairs is excluded at 95% confidence level for T quark masses up to 1.54 TeV and B quark masses up to 1.56 TeV, depending on the branching fractions assumed, with maximal sensitivity to decay modes that include multiple top quarks. The limits obtained in this search are the strongest limits to date for $\mathrm{T\overline{T}}$ production, excluding masses below 1.48 TeV for all decays to third generation quarks, and are the strongest limits to date for $\mathrm{B\overline{B}}$ production with B quark decays to tW

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at s= \sqrt{s}= 13 TeV

A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark ($\tilde{\mathrm{t}}_{1}$), is presented. The search targets the four-body decay of the $\tilde{\mathrm{t}}_{1}$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino ($\tilde{\chi}_{1}^{0}$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between $m(\tilde{\mathrm{t}}_{1})$ and $m(\tilde{\chi}_{1}^{0})$. The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for $m(\tilde{\mathrm{t}}_{1}) - m(\tilde{\chi}_{1}^{0}) =$ 10 and 80 GeV, respectively.A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (${\overset{\sim }{\textrm{t}}}_1$), is presented. The search targets the four-body decay of the ${\overset{\sim }{\textrm{t}}}_1$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (${\overset{\sim }{\chi}}_1^0$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{−1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(${\overset{\sim }{\textrm{t}}}_1$) and m(${\overset{\sim }{\chi}}_1^0$). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(${\overset{\sim }{\textrm{t}}}_1$) − m(${\overset{\sim }{\chi}}_1^0$) = 10 and 80 GeV, respectively.[graphic not available: see fulltext]A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark ($\tilde{\mathrm{t}}_1$), is presented. The search targets the four-body decay of the $\tilde{\mathrm{t}}_1$, which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino ($\tilde{\chi}^0_1$), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between $m(\tilde{\mathrm{t}}_1)$ and $m(\tilde{\chi}^0_1)$. The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for $m(\tilde{\mathrm{t}}_1) - m(\tilde{\chi}^0_1$) = 10 and 80 GeV, respectively

Search for nonresonant Higgs boson pair production in the four leptons plus twob jets final state in proton-proton collisions at s \sqrt{s} = 13 TeV

The first search for nonresonant production of Higgs boson pairs (HH) with one H decaying into four leptons and the other into a pair of b quarks is presented, using proton-proton collisions recorded at a center-of-mass energy of $\sqrt{s}$ = 13 TeV by the CMS experiment. The analyzed data correspond to an integrated luminosity of 138 fb$^{−1}$. A 95% confidence level upper limit of 32.4 is set on the signal strength modifier μ, defined as the ratio of the observed HH production rate in the $\textrm{HH}\to {\textrm{ZZ}}^{\ast}\textrm{b}\overline{\textrm{b}}\to 4\ell \textrm{b}\overline{\textrm{b}}$ decay channel to the standard model (SM) expectation. Possible modifications of the H trilinear coupling λ$_{HHH}$ with respect to the SM value are investigated. The coupling modifier κ$_{λ}$, defined as λ$_{HHH}$ divided by its SM prediction, is constrained to be within the observed (expected) range −8.8 (−9.8) < κ$_{λ}$< 13.4 (15.0) at 95% confidence level.[graphic not available: see fulltext

Search for long-lived particles decaying to a pair of muons in proton-proton collisions at s \sqrt{s} = 13 TeV

An inclusive search for long-lived exotic particles decaying to a pair of muons is presented. The search uses data collected by the CMS experiment at the CERN LHC in proton-proton collisions at $\sqrt{s}$ = 13 TeV in 2016 and 2018 and corresponding to an integrated luminosity of 97.6 fb$^{−1}$. The experimental signature is a pair of oppositely charged muons originating from a common secondary vertex spatially separated from the pp interaction point by distances ranging from several hundred μm to several meters. The results are interpreted in the frameworks of the hidden Abelian Higgs model, in which the Higgs boson decays to a pair of long-lived dark photons Z$_{D}$, and of a simplified model, in which long-lived particles are produced in decays of an exotic heavy neutral scalar boson. For the hidden Abelian Higgs model with m(Z$_{D}$) greater than 20 GeV and less than half the mass of the Higgs boson, they provide the best limits to date on the branching fraction of the Higgs boson to dark photons for cτ(Z$_{D}$) (varying with m(Z$_{D}$)) between 0.03 and ≈0.5 mm, and above ≈0.5 m. Our results also yield the best constraints on long-lived particles with masses larger than 10 GeV produced in decays of an exotic scalar boson heavier than the Higgs boson and decaying to a pair of muons.[graphic not available: see fulltext