The business of genomic testing: a survey of early adopters

Purpose: The practice of genomic (or personalized ) medicine requires the availability of appropriate diagnostic testing. Our study objective was to identify the reasons for health systems to bring next-generation Sequencing into their clinical laboratories and to understand the process by which such decisions were made. Such information may be of value to other health systems seeking to provide next-generation sequencing-testing to their patient populations. Methods: A standardized open-ended interview was conducted With the laboratory medical directors and/or department of pathology chairs of 13 different academic institutions in 10 different states. Results: Genomic testing for cancer dominated the institutional decision making, with three primary reasons: more effective delivery of cancer care, the perceived need for institutional leadership in the field of genomics, and the premise that genomics will eventually be cost-effective. Barriers to implementation included implementation cost; the time and effort needed to maintain this newer testing; challenges in interpreting genetic variants; establishing the bioinformatics infrastructure; and curating data from medical, ethical, and legal standpoints. Ultimate success depended on alignment with institutional strengths and priorities and working closely with institutional clinical programs. Conclusion: These early adopters uniformly viewed genomic analysis as an imperative for developing their expertise in the implementation and practice of genomic medicine

The Streptomycin-Treated Mouse Intestine Selects \u3cem\u3eEscherichia coli envZ\u3c/em\u3e Missense Mutants That Interact with Dense and Diverse Intestinal Microbiota

Previously, we reported that the streptomycin-treated mouse intestine selected nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect. Immun. 73:8039–8049, 2005). Here, we report that the 10 to 20% remaining motile E. coli MG1655 are envZ missense mutants that are also better colonizers of the mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655 ΔflhD, and one of the envZ missense mutants, E. coli MG1655 mot-1, were studied further. E. coli MG1655 mot-1 is more resistant to bile salts and colicin V than E. coli MG1655 ΔflhD and grows ca. 15% slower in vitro in mouse cecal mucus and on several sugars present in mucus compared to E. coli MG1655 ΔflhD but grows 30% faster on galactose. Moreover, E. coli MG1655 mot-1 and E. coli MG1655 ΔflhD appear to colonize equally well in one intestinal niche, but E. coli MG1655 mot-1 appears to use galactose to colonize a second, smaller intestinal niche either not colonized or colonized poorly by E. coli MG1655 ΔflhD. Evidence is also presented that E. coli MG1655 is a minority member of mixed bacterial biofilms in the mucus layer of the streptomycin-treated mouse intestine. We offer a hypothesis, which we call the “Restaurant” hypothesis, that explains how nutrient acquisition in different biofilms comprised of different anaerobes can account for our results

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio

Measurement of the semileptonic charge asymmetry in B0 meson mixing with the D0 detector

We present a measurement of the semileptonic mixing asymmetry for B0 mesons, a^d_{sl}, using two independent decay channels: B0 -> mu+D-X, with D- -> K+pi-pi-; and B0 -> mu+D*-X, with D*- -> antiD0 pi-, antiD0 -> K+pi- (and charge conjugate processes). We use a data sample corresponding to 10.4 fb^{-1} of ppbar collisions at sqrt(s) = 1.96 TeV, collected with the D0 experiment at the Fermilab Tevatron collider. We extract the charge asymmetries in these two channels as a function of the visible proper decay length (VPDL) of the B0 meson, correct for detector-related asymmetries using data-driven methods, and account for dilution from charge-symmetric processes using Monte Carlo simulation. The final measurement combines four signal VPDL regions for each channel, yielding a^d_{sl} = [0.68 \pm 0.45 \text{(stat.)} \pm 0.14 \text{(syst.)}]%. This is the single most precise measurement of this parameter, with uncertainties smaller than the current world average of B factory measurements.Comment: Version includes minor textual changes following peer review by journal, most notably the updating of Ref. [21] to reflect the most recent publicatio

Search for Zgamma events with large missing transverse energy in ppbar collisions at sqrt(s)=1.96 TeV

We present the first search for supersymmetry (SUSY) in Zgamma final states with large missing transverse energy using data corresponding to an integrated luminosity of 6.2 fb-1 collected with the D0 experiment in ppbar collisions at sqrt(s)=1.96 TeV. This signature is predicted in gauge-mediated SUSY-breaking models, where the lightest neutralino is the next-to-lightest supersymmetric particle (NLSP) and is produced in pairs, possibly through decay from heavier supersymmetric particles. The NLSP can decay either to a Z boson or a photon and an associated gravitino that escapes detection. We exclude this model at the 95% C.L. for SUSY breaking scales of Lambda < 87 TeV, corresponding to neutralino masses of < 151 GeV.Comment: submitted to Phys. Rev. Let

Search for B0→π0π0B^{0}\to \pi^{0}\pi^{0} Decay

We have searched for the charmless hadronic decay of B0 mesons into two neutral pions. Using 9.13fb^-1 taken at the Upsilon(4S) with the CLEO detector, we obtain an improved upper limit for the branching fraction BR(B0-->pi0pi0) < 5.7*10^-6 at the 90% confidence level.Comment: pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Journal Staff

We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar &lt; 1.0 and transverse momenta 30 &lt; p(T)(gamma) &lt; 200 GeV. The b-quark jets are required to have p(T)(jet) &gt; 15 GeVand vertical bar y(jet)vertical bar &lt; 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators

Measurement of the semileptonic charge asymmetry using Bs^0 -> D_s mu X decays

We present a measurement of the time-integrated flavor-specific semileptonic charge asymmetry in the decays of Bs mesons that have undergone flavor mixing, a^s_ls, using B_s^0 (barB_s^0) -> D_s^-/+ mu^+/- X decays, with D_s^-/+ -> phi pi^-/+ and phi K^+ K^-, using 10.4 fb^-1 of proton-antiproton collisions collected by the D0 detector during Run II at the Fermilab Tevatron Collider. A fit to the difference between the time-integrated D_s^-$ and D_s^+ mass distributions of the B_s^0 and barB^0_s candidates yields the flavor-specific asymmetry a^s_ls = [-1.12 pm 0.74 (stat) +/-0.17 (syst)]% which is the most precise measurement and in agreement with the standard model prediction.Comment: 7 pages, 3 figures (updated with changes made in journal review process

Search for the Higgs boson in lepton, tau and jets final states

We present a search for the standard model Higgs boson in final states with an electron or muon and a hadronically decaying tau lepton in association with two or more jets using 9.7 fb^{-1} of Run II Fermilab Tevatron Collider data collected with the D0 detector. The analysis is sensitive to Higgs boson production via gluon fusion, associated vector boson production, and vector boson fusion, followed by the Higgs boson decay to tau lepton pairs or to W boson pairs. The ratios of 95% C.L. upper limits on the cross section times branching ratio to those predicted by the standard model are obtained for orthogonal subsamples that are enriched in either H -> tau tau decays or H -> WW decays, and for the combination of these subsample limits. The observed and expected limit ratios for the combined subsamples at a Higgs boson mass of 125 GeV are 11.3 and 9.0 respectively