Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities

Vuorio A, Watts GF, Schneider WJ, Tsimikas S, Kovanen PT (Mehilainen Airport Health Centre, Vantaa; University of Helsinki, Helsinki, Finland; University of Western Australia, Perth, Australia; Royal Perth Hospital, Perth, Australia; Medical University of Vienna, Vienna, Austria; University of California San Diego, La Jolla, CA, USA; Wihuri Research Institute, Helsinki, Finland). Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities (Review). J Intern Med 2020; 287: 2-18. There is compelling evidence that the elevated plasma lipoprotein(a) [Lp(a)] levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. Like low-density lipoprotein (LDL) particles, Lp(a) particles contain cholesterol and promote atherosclerosis. In addition, Lp(a) particles contain strongly proinflammatory oxidized phospholipids and a unique apoprotein, apo(a), which promotes the growth of an arterial thrombus. At least one in 250 individuals worldwide suffer from the heterozygous form of familial hypercholesterolemia (HeFH), a condition in which LDL-cholesterol (LDL-C) is significantly elevated since birth. FH-causing mutations in the LDL receptor gene demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations and elevated Lp(a) levels are present in 30-50% of patients with HeFH. The cumulative burden of two genetically determined pro-atherogenic lipoproteins, LDL and Lp(a), is a potent driver of ASCVD in HeFH patients. Statins are the cornerstone of treatment of HeFH, but they do not lower the plasma concentrations of Lp(a). Emerging therapies effectively lower Lp(a) by as much as 90% using RNA-based approaches that target the transcriptional product of the LPA gene. We are now approaching the dawn of an era, in which permanent and significant lowering of the high cholesterol burden of HeFH patients can be achieved. If outcome trials of novel Lp(a)-lowering therapies prove to be safe and cost-effective, they will provide additional risk reduction needed to effectively treat HeFH and potentially lower the CVD risk in these high-risk patients even more than currently achieved with LDL-C lowering alone.Peer reviewe

Dependence of the ttˉt\bar{t} production cross section on the transverse momentum of the top quark

We present a measurement of the differential cross section for $t\bar{t}$ events produced in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV as a function of the transverse momentum ($p_T$) of the top quark. The selected events contain a high-$p_T$ lepton ($\ell$), four or more jets, and a large imbalance in $p_T$, and correspond to 1 fb${}^{-1}$ of integrated luminosity recorded with the D0 detector. Each event must have at least one candidate for a $b$ jet. Objects in the event are associated through a constrained kinematic fit to the $t\bar{t}\to WbW\bar{b} \to \ell\nu b q\bar{q}'\bar{b}$ process. Results from next-to-leading-order perturbative QCD calculations agree with the measured differential cross section. Comparisons are also provided to predictions from Monte Carlo event generators using QCD calculations at different levels of precision.Comment: 8 pages, 6 figures, 4 tables, updated to reflect the published versio

Search for single top quarks in the tau+jets channel using 4.8 fb−1^{-1} of ppˉp\bar{p} collision data

We present the first direct search for single top quark production using tau leptons. The search is based on 4.8 fb$^{-1}$ of integrated luminosity collected in $p\bar{p}$ collisions at $\sqrt{s}$=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. We select events with a final state including an isolated tau lepton, missing transverse energy, two or three jets, one or two of them $b$ tagged. We use a multivariate technique to discriminate signal from background. The number of events observed in data in this final state is consistent with the signal plus background expectation. We set in the tau+jets channel an upper limit on the single top quark cross section of \TauLimObs pb at the 95% C.L. This measurement allows a gain of 4% in expected sensitivity for the observation of single top production when combining it with electron+jets and muon+jets channels already published by the D0 collaboration with 2.3 fb$^{-1}$ of data. We measure a combined cross section of \SuperCombineXSall pb, which is the most precise measurement to date.Comment: 12 pages, 5 figure

Measurement of Z/gamma*+jet+X angular distributions in ppbar collisions at sqrt{s}=1.96 TeV

We present the first measurements at a hadron collider of differential cross sections for Z+jet+X production in delta phi(Z, jet), |delta y(Z, jet)| and |y_boost(Z, jet)|. Vector boson production in association with jets is an excellent probe of QCD and constitutes the main background to many small cross section processes, such as associated Higgs production. These measurements are crucial tests of the predictions of perturbative QCD and current event generators, which have varied success in describing the data. Using these measurements as inputs in tuning event generators will increase the experimental sensitivity to rare signals.Comment: Published in Physics Letters B 682 (2010), pp. 370-380. 15 pages, 6 figure

Search for the standard model Higgs boson in tau final states

We present a search for the standard model Higgs boson using hadronically decaying tau leptons, in 1 inverse femtobarn of data collected with the D0 detector at the Fermilab Tevatron ppbar collider. We select two final states: tau plus missing transverse energy and b jets, and tau+ tau- plus jets. These final states are sensitive to a combination of associated W/Z boson plus Higgs boson, vector boson fusion and gluon-gluon fusion production processes. The observed ratio of the combined limit on the Higgs production cross section at the 95% C.L. to the standard model expectation is 29 for a Higgs boson mass of 115 GeV.Comment: publication versio

Double parton interactions in photon+3 jet events in ppbar collisions sqrt{s}=1.96 TeV

We have used a sample of photon+3 jets events collected by the D0 experiment with an integrated luminosity of about 1 fb^-1 to determine the fraction of events with double parton scattering (f_DP) in a single ppbar collision at sqrt{s}=1.96 TeV. The DP fraction and effective cross section (sigma_eff), a process-independent scale parameter related to the parton density inside the nucleon, are measured in three intervals of the second (ordered in pT) jet transverse momentum pT_jet2 within the range 15 < pT_jet2 < 30 GeV. In this range, f_DP varies between 0.23 < f_DP < 0.47, while sigma_eff has the average value sigma_eff_ave = 16.4 +- 0.3(stat) +- 2.3(syst) mb.Comment: 15 pages, 13 figure

Search for W' bosons decaying to an electron and a neutrino with the D0 detector

This Letter describes the search for a new heavy charged gauge boson W' decaying into an electron and a neutrino. The data were collected with the D0 detector at the Fermilab Tevatron proton-antiproton Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of about 1 inverse femtobarn. Lacking any significant excess in the data in comparison with known processes, an upper limit is set on the production cross section times branching fraction, and a W' boson with mass below 1.00 TeV can be excluded at the 95% C.L., assuming standard-model-like couplings to fermions. This result significantly improves upon previous limits, and is the most stringent to date.Comment: submitted to Phys. Rev. Let

Measurements of differential cross sections of Z/gamma*+jets+X events in proton anti-proton collisions at sqrt{s}=1.96 TeV

We present cross section measurements for Z/gamma*+jets+X production, differential in the transverse momenta of the three leading jets. The data sample was collected with the D0 detector at the Fermilab Tevatron proton anti-proton collider at a center-of-mass energy of 1.96 TeV and corresponds to an integrated luminosity of 1 fb-1. Leading and next-to-leading order perturbative QCD predictions are compared with the measurements, and agreement is found within the theoretical and experimental uncertainties. We also make comparisons with the predictions of four event generators. Two parton-shower-based generators show significant shape and normalization differences with respect to the data. In contrast, two generators combining tree-level matrix elements with a parton shower give a reasonable description of the the shapes observed in data, but the predicted normalizations show significant differences with respect to the data, reflecting large scale uncertainties. For specific choices of scales, the normalizations for either generator can be made to agree with the measurements.Comment: Published in PLB. 11 pages, 3 figure

Measurement of the B0_s semileptonic branching ratio to an orbitally excited D_s** state, Br(B0_s -> Ds1(2536) mu nu)

In a data sample of approximately 1.3 fb-1 collected with the D0 detector between 2002 and 2006, the orbitally excited charm state D_s1(2536) has been observed with a measured mass of 2535.7 +/- 0.6 (stat) +/- 0.5 (syst) MeV via the decay mode B0_s -> D_s1(2536) mu nu X. A first measurement is made of the branching ratio product Br(b(bar) -> D_s1(2536) mu nu X).Br(D_s1(2536)->D* K0_S). Assuming that D_s1(2536) production in semileptonic decay is entirely from B0_s, an extraction of the semileptonic branching ratio Br(B0_s -> D_s1(2536) mu nu X) is made.Comment: 7 pages, 2 figures, LaTeX, version with minor changes as accepted by Phys. Rev. Let

Measurement of the t-channel single top quark production cross section

The D0 collaboration reports direct evidence for electroweak production of single top quarks through the t-channel exchange of a virtual W boson. This is the first analysis to isolate an individual single top quark production channel. We select events containing an isolated electron or muon, missing transverse energy, and two, three or four jets from 2.3 fb^-1 of ppbar collisions at the Fermilab Tevatron Collider. One or two of the jets are identified as containing a b hadron. We combine three multivariate techniques optimized for the t-channel process to measure the t- and s-channel cross sections simultaneously. We measure cross sections of 3.14 +0.94 -0.80 pb for the t-channel and 1.05 +-0.81 pb for the s-channel. The measured t-channel result is found to have a significance of 4.8 standard deviations and is consistent with the standard model prediction.Comment: 7 pages, 6 figure