Malcolm John

Abstract:

The first observation of the D0→π+π−μ+μ− and D0→K+K−μ+μ− decays is reported using a sample of proton-proton collisions collected by LHCb at a center-of-mass energy of 8 TeV, and corresponding to 2  fb^−1 of integrated luminosity. The corresponding branching fractions are measured using as normalization the decay D0→K−π+[μ+μ−]ρ0/ω, where the two muons are consistent with coming from the decay of a ρ0 or ω meson. The results are B(D0→π+π−μ+μ−)=(9.64±0.48±0.51±0.97)×10^−7 and B(D0→K+K−μ+μ−)=(1.54±0.27±0.09±0.16)×10^−7, where the uncertainties are statistical, systematic, and due to the limited knowledge of the normalization branching fraction. The dependence of the branching fraction on the dimuon mass is also investigated.

Abstract:

Production of prompt D 0 mesons is studied in proton-lead and lead-proton collisions recorded at the LHCb detector at the LHC. The data sample corresponds to an integrated luminosity of 1.58±0.02 nb −1 recorded at a nucleon-nucleon centre-of-mass energy of sNN=5 TeV. Measurements of the differential cross-section, the forward-backward production ratio and the nuclear modification factor are reported using D 0 candidates with transverse momenta less than 10 GeV/c and rapidities in the ranges 1.5 < y ∗ < 4.0 and −5.0 < y ∗ < −2.5 in the nucleon-nucleon centre-of-mass system.

Abstract:

Objective

Long-acting rilpivirine is a candidate for pre-exposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (RT-E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing Human Leukocyte Antigen (HLA)-B*18 where RT-E138X arises as an immune escape mutation. We investigate the global prevalence, B*18-linkage and replicative cost of RT-E138X and its regional implications for rilpivirine PrEP.

Methods

We analysed linked RT-E138X/HLA data from 7772 patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global RT-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in vitro replication as a surrogate of mutation stability following transmission.

Results

RT-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B*18-positive individuals globally (p=3.5x10-20) and in all HIV-1 subtypes except A. RT-E138X and B*18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman’s R=0.75; p=7.6x10-4) and in unlinked HIV/HLA data from 43 countries (Spearman's R=0.34, p=0.02). Notably, RT-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. Sub-Saharan Africa, Southeastern Europe) where B*18 is more common. This, along with the observation that RT-E138X variants do not confer in vitro replicative costs, supports their persistence and ongoing accumulation in circulation over time.

Conclusions

Results illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional RT-E138X surveillance should be undertaken before use of rilpivirine PrEP.

Abstract:

We report on a measurement of the flavor-specific B0s lifetime and of the D−s lifetime using proton-proton collisions at center-of-mass energies of 7 and 8 TeV, collected by the LHCb experiment and corresponding to 3.0 fb^-1 of integrated luminosity. Approximately 407 000 B0s → D(*)−s μ+νμ decays are partially reconstructed in the K+K−π−μ+ final state. The B0s and D−s natural widths are determined using, as a reference, kinematically similar B0 → D(*)−μ+νμ decays reconstructed in the same final state. The resulting differences between widths of B0s and B0 mesons and of D−s and D− mesons are ΔΓ(B) = −0.0115 ± 0.0053(stat) ± 0.0041(syst) ps^-1 and ΔΓ(D)=1.0131±0.0117(stat)±0.0065(syst) ps^-1, respectively. Combined with the known B0 and D− lifetimes, these yield the flavor-specific B0s lifetime, τfsB0s=1.547±0.013(stat)±0.010(syst)±0.004(τB)  ps and the D−s lifetime, τD−s=0.5064±0.0030(stat)±0.0017(syst)±0.0017(τD)  ps. The last uncertainties originate from the limited knowledge of the B0 and D− lifetimes. The results improve upon current determinations.