Publications by authors named "Kirkby D"

Characterizing the human immunodeficiency virus (HIV) reservoir that endures despite antiretroviral therapy (ART) is critical to cure efforts. We observed that the oldest proviruses persisting during ART were exclusively defective, while intact proviruses (and rebound HIV) dated to nearer ART initiation. This helps explain why studies that sampled sub-genomic proviruses on-ART (which are largely defective) routinely found sequences dating to early infection, whereas those that sampled replication-competent HIV found almost none.

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In order to cure HIV, we need to better understand the within-host evolutionary origins of the small reservoir of genome-intact proviruses that persists within infected cells during antiretroviral therapy (ART). Most prior studies on reservoir evolutionary dynamics however did not discriminate genome-intact proviruses from the vast background of defective ones. We reconstructed within-host pre-ART HIV evolutionary histories in six individuals and leveraged this information to infer the ages of intact and defective proviruses sampled after an average >9 years on ART, along with the ages of rebound and low-level/isolated viremia occurring during this time.

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The greatest HIV-1 genetic diversity is found in West/Central Africa due to the pandemic’s origins in this region, but this diversity remains understudied. We characterized HIV-1 subtype diversity (from both sub-genomic and full-genome viral sequences), drug resistance and coreceptor usage in 103 predominantly (90%) antiretroviral-naive individuals living with HIV-1 in Ghana. Full-genome HIV-1 subtyping confirmed the circulating recombinant form CRF02_AG as the dominant (53.

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SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have immunologically assessed serial Omicron infections. We characterized SARS-CoV-2 humoral responses in an individual who acquired laboratory-confirmed Omicron BA.1.

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Despite the effectiveness of direct-acting antiviral agents in treating hepatitis C virus (HCV), cases of treatment failure have been associated with the emergence of resistance-associated substitutions. To better guide clinical decision-making, we developed and validated a near-whole-genome HCV genotype-independent next-generation sequencing strategy. HCV genotype 1-6 samples from direct-acting antiviral agent treatment-naïve and -treated HCV-infected individuals were included.

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Article Synopsis
  • The Intact Proviral DNA Assay (IPDA) is a droplet digital PCR-based method designed to accurately measure the amount of intact HIV-1 in the body, which is crucial for understanding HIV-1 persistence.
  • In a study of a diverse group of people with HIV-1 subtype B in North America, the IPDA experienced a 28% failure rate due to variations in the virus, known as polymorphisms.
  • This variability can cause the IPDA to inaccurately estimate the size of the HIV-1 reservoir, highlighting the need to consider HIV-1 diversity before widely using the IPDA in clinical trials for HIV-1 treatment and remission.
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Next generation sequencing (NGS) is a trending new standard for genotypic HIV-1 drug resistance (HIVDR) testing. Many NGS HIVDR data analysis pipelines have been independently developed, each with variable outputs and data management protocols. Standardization of such analytical methods and comparison of available pipelines are lacking, yet may impact subsequent HIVDR interpretation and other downstream applications.

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Limited access to HIV drug resistance testing in low- and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously.

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We present results of a search for CP violation in B0- B0 mixing with the BABAR detector. We select a sample of B0→D*- Xℓ+ ν decays with a partial reconstruction method and use kaon tagging to assess the flavor of the other B meson in the event. We determine the CP violating asymmetry ACP≡[N(B0B0)-N(B0B0)]/[N(B0B0)+N(B0B0)]=(0.

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We measure the mass difference Δm0 between the D*(2010)+ and the D0 and the natural linewidth Γ of the transition D*(2010)+ → D0π+. The data were recorded with the BABAR detector at center-of-mass energies at and near the Υ(4S) resonance, and correspond to an integrated luminosity of approximately 477  fb(-1). The D0 is reconstructed in the decay modes D0 → K- π+ and D0 → K- π+ π- π+.

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Baumard et al. attribute to humans a sense of fairness. However, the properties of this sense are so underspecified that the evolutionary account offered is not well-motivated.

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Although CP violation in the B meson system has been well established by the B factories, there has been no direct observation of time-reversal violation. The decays of entangled neutral B mesons into definite flavor states (B(0) or B(0)), and J/ψK(L)(0) or ccK(S)(0) final states (referred to as B(+) or B(-)), allow comparisons between the probabilities of four pairs of T-conjugated transitions, for example, B(0) → B(-) and B(-) → B(0), as a function of the time difference between the two B decays. Using 468 × 10(6) BB pairs produced in Υ(4S) decays collected by the BABAR detector at SLAC, we measure T-violating parameters in the time evolution of neutral B mesons, yielding ΔS(T)(+) = -1.

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The photon spectrum in the inclusive electromagnetic radiative decays of the B meson, B → X(s)γ plus B → X(d)γ, is studied using a data sample of (382.8 ± 4.2) × 10(6)Υ(4S) → BB decays collected by the BABAR experiment at SLAC.

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Based on the full BABAR data sample, we report improved measurements of the ratios R(D(*))=B(B[over ¯]→D(*)τ(-)ν[over ¯](τ))/B(B[over ¯]→D(*)ℓ(ℓ)(-)ν[over ¯](ℓ)), where ℓ is either e or μ. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D)=0.

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Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb(-1) of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the standard model-dark-sector mixing angle and the dark-sector coupling constant.

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We search for hadronic decays of a light Higgs boson (A(0)) produced in radiative decays of an Υ(2S) or Υ(3S) meson, Υ→γA(0). The data have been recorded by the BABAR experiment at the Υ(3S) and Υ(2S) center-of-mass energies and include (121.3±1.

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We report the observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) based on 342  fb(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B- → D(s)((*)+) K- ℓ- ν(ℓ)) = [6.

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We search for single-photon decays of the Υ(1S) resonance, Υ → γ + invisible, where the invisible state is either a particle of definite mass, such as a light Higgs boson A⁰, or a pair of dark matter particles, χχ. Both A⁰ and χ are assumed to have zero spin. We tag Υ(1S) decays with a dipion transition Υ(2S) → π⁺π⁻Υ(1S) and look for events with a single energetic photon and significant missing energy.

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We present a search for f(J)(2220) production in radiative J/ψ→γf(J)(2220) decays using 460  fb⁻¹ of data collected with the BABAR detector at the SLAC PEP-II e(+)e⁻ collider. The f(J)(2220) is searched for in the decays to K(+)K⁻ and K(S)⁰K(S)⁰. No evidence of this resonance is observed, and 90% confidence level upper limits on the product of the branching fractions for J/ψ→γf(J)(2220) and f(J)(2220)→K(+)K⁻(K(S)⁰K(S)⁰) as a function of spin and helicity are set at the level of 10⁻⁵, below the central values reported by the Mark III experiment.

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We report a direct measurement of D0-D0 mixing parameters through a time-dependent amplitude analysis of the Dalitz plots of D(0) → K(S)(0) π+ π- and, for the first time, D0 → K(S)(0)K+ K- decays. The low-momentum pion π(s)(+) in the decay D*+ → D0 π(s)(+) identifies the flavor of the neutral D meson at its production. Using 468.

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Using 467  fb(-1) of e+e- annihilation data collected with the BABAR detector, we measure (B(τ- → μ- ν(μ) ν(τ)))/(B(τ- → e- ν(e) ν(τ))) =(0.9796±0.0016±0.

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We report the measurement of the Cabibbo-Kobayashi-Maskawa CP-violating angle γ through a Dalitz plot analysis of neutral D-meson decays to K(S)(0) π+ π- and K(S)(0) K+ K- produced in the processes B∓ → DK∓, B∓ D* K∓ with D* → Dπ(0), Dγ, and B∓ → DK*∓ with K*∓ → K(S)(0) π∓, using 468 million BB pairs collected by the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure γ = (68 ± 14 ± 4 ± 3)° (modulo 180°), where the first error is statistical, the second is the experimental systematic uncertainty, and the third reflects the uncertainty in the description of the neutral D decay amplitudes. This result is inconsistent with γ = 0 (no direct CP violation) with a significance of 3.

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The ratio R(τμ)(Υ(1S))=Γ(Υ(1S)→τ+ τ-)/Γ(Υ(1S)→μ+ μ-) is measured using a sample of (121.8±1.2)×10(6)Υ(3S) events recorded by the BABAR detector.

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Charged-lepton flavor-violating processes are unobservable in the standard model, but they are predicted to be enhanced in several extensions to the standard model, including supersymmetry and models with leptoquarks or compositeness. We present a search for such processes in a sample of 99x10(6)Upsilon(2S) decays and 117x10(6)Upsilon(3S) decays collected with the BABAR detector. We place upper limits on the branching fractions B(Upsilon(nS)-->e(+/-)tau(-/+)) and B(Upsilon(nS)-->mu(+/-)tau(-/+)) (n=2,3) at the 10(-6) level and use these results to place lower limits of order 1 TeV on the mass scale of charged-lepton flavor-violating effective operators.

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