The administration of antiretrovirals (ARVs) for HIV pre-exposure prophylaxis (PrEP) is highly efficacious and may benefit from new long-acting (LA) drug delivery approaches. This paper describes a subcutaneous, reservoir-style implant for the LA delivery of tenofovir alafenamide (TAF) and documents the preclinical assessment of implant safety and pharmacokinetics (PK) in New Zealand White (NZW) rabbits (3 groups of n = 5), beagle dogs (2 groups of n = 6), and rhesus macaques (2 groups of n = 3). Placebo implants were placed in rabbits (n = 10) and dogs (n = 12). Implant parameters, including selection of the TAF form, choice of excipient, and PCL formulation were tuned to achieve targeted concentrations of the active anabolite of TAF, tenofovir diphosphate (TFV-DP), within peripheral blood mononuclear cells (PBMCs) and mucosal tissues relevant to HIV transmission. Sustained concentrations of TFV-DP in PBMCs over 100 fmol/10(6) cells were achieved in all animal species indicating that the implants effectively delivered TAF for 3-6 months. Unlike placebo implants without TAF, all active implants resulted in local adverse events (AEs) proximal to the implant ranging in severity from mild to moderate and included dermal inflammation and necrosis across all species. Despite these AEs, the implant performed as designed and achieved a constant drug release profile, supporting the continued development of this drug delivery platform.

OBJECTIVES:To advance the initiative of ending the global epidemic, long-lasting HIV protection is needed through sustained release of antiretroviral drugs for months to years. We investigated in macaques the safety and efficacy of biodegradable polycaprolactone implants releasing tenofovir alafenamide for HIV pre-exposure prophylaxis (PrEP).METHODS:Implants were administered subcutaneously in the arm using a contraceptive trocar. Efficacy against vaginal simian-HIV (SHIV) infection was investigated in six pigtailed macaques that received two tenofovir alafenamide implants (0.35 mg/day), one in each arm, for a total release rate of tenofovir alafenamide at 0.7 mg/day. Macaques were exposed to SHIV twice weekly for 6 weeks. Statistical analyses were used to compare outcome with eight untreated controls. Histological assessments were performed on skin biopsies collected near implantation sites.RESULTS:Median (range) tenofovir diphosphate level in PBMCs was 1519 (1068-1898) fmol/106 cells. All macaques with tenofovir alafenamide implants were protected against vaginal SHIV infection. In contrast, 7/8 controls were infected after a median of 4 SHIV exposures (P = 0.0047). Histological assessment of tissues near tenofovir alafenamide implant sites showed inflammation and necrosis in 5/6 animals, which were not evident by visual inspection.CONCLUSIONS:We demonstrated complete protection against vaginal SHIV infection with two implants releasing a total of 0.7 mg of tenofovir alafenamide per day. We also identified tenofovir diphosphate concentrations in PBMCs associated with complete vaginal protection. Consistent with previous findings, we observed adverse local toxicity and necrosis near the tenofovir alafenamide implant site. Improved tenofovir alafenamide implants that are safe and maintain high efficacy have the potential to provide long-lasting protection against vaginal HIV infection.

Cross-sections and angular distributions for hadronic and lepton pair final states in e+e− collisions at a centre-of-mass energy near 189 GeV, measured with the OPAL detector at LEP, are presented and compared with the predictions of the Standard Model. The results are used to measure the energy dependence of the electromagnetic coupling constant αem, and to place limits on new physics as described by four-fermion contact interactions or by the exchange of a new heavy particle such as a sneutrino in supersymmetric theories with R-parity violation. A search for the indirect effects of the gravitational interaction in extra dimensions on the μ+μ− and τ+τ− final states is also presented. Submitted to European Journal of Physics C The OPAL Collaboration G.Abbiendi, K.Ackerstaff, G.Alexander, J. Allison, K.J.Anderson, S.Anderson, S.Arcelli, S.Asai, S.F.Ashby, D.Axen, G.Azuelos, A.H.Ball, E. Barberio, R.J. Barlow, J.R.Batley, S. Baumann, J. Bechtluft, T.Behnke, K.W.Bell, G.Bella, A.Bellerive, S. Bentvelsen, S. Bethke, S. Betts, O.Biebel, A.Biguzzi, I.J. Bloodworth, P. Bock, J. Böhme, O.Boeriu, D.Bonacorsi, M.Boutemeur, S. Braibant, P. Bright-Thomas, L. Brigliadori, R.M.Brown, H.J. Burckhart, P.Capiluppi, R.K.Carnegie, A.A.Carter, J.R.Carter, C.Y.Chang, D.G.Charlton, D.Chrisman, C.Ciocca, P.E.L.Clarke, E.Clay, I. Cohen, J.E.Conboy, O.C.Cooke, J. Couchman, C.Couyoumtzelis, R.L.Coxe, M.Cuffiani, S.Dado, G.M.Dallavalle, S.Dallison, R.Davis, S.De Jong, A. de Roeck, P.Dervan, K.Desch, B.Dienes, M.S.Dixit, M.Donkers, J.Dubbert, E.Duchovni, G.Duckeck, I.P.Duerdoth, P.G.Estabrooks, E. Etzion, F. Fabbri, A. Fanfani, M. Fanti, A.A. Faust, L. Feld, P. Ferrari, F. Fiedler, M. Fierro, I. Fleck, A. Frey, A. Fürtjes, D.I. Futyan, P.Gagnon, J.W.Gary, G.Gaycken, C.Geich-Gimbel, G.Giacomelli, P.Giacomelli, W.R.Gibson, D.M.Gingrich, D.Glenzinski, J.Goldberg, W.Gorn, C.Grandi, K.Graham, E.Gross, J.Grunhaus, M.Gruwé, C.Hajdu G.G.Hanson, M.Hansroul, M.Hapke, K.Harder, A.Harel, C.K.Hargrove, M.Harin-Dirac, M.Hauschild, C.M.Hawkes, R.Hawkings, R.J.Hemingway, G.Herten, R.D.Heuer, M.D.Hildreth, J.C.Hill, P.R.Hobson, A.Hocker, K.Hoffman, R.J.Homer, A.K.Honma, D.Horváth, K.R.Hossain, R.Howard, P.Hüntemeyer, P. Igo-Kemenes, D.C. Imrie, K. Ishii, F.R. Jacob, A. Jawahery, H. Jeremie, M. Jimack, C.R. Jones, P. Jovanovic, T.R. Junk, N.Kanaya, J.Kanzaki, D.Karlen, V.Kartvelishvili, K.Kawagoe, T.Kawamoto, P.I.Kayal, R.K.Keeler, R.G.Kellogg, B.W.Kennedy, D.H.Kim, A.Klier, T.Kobayashi, M.Kobel, T.P.Kokott, M.Kolrep, S.Komamiya, R.V.Kowalewski, T.Kress, P.Krieger, J. von Krogh, T.Kuhl, P.Kyberd, G.D. Lafferty, H. Landsman, D. Lanske, J. Lauber, I. Lawson, J.G. Layter, D. Lellouch, J. Letts, L. Levinson, R. Liebisch, J. Lillich, B. List, C. Littlewood, A.W.Lloyd, S.L. Lloyd, F.K. Loebinger, G.D. Long, M.J. Losty, J. Lu, J. Ludwig, D. Liu, A.Macchiolo, A.Macpherson, W.Mader, M.Mannelli, S.Marcellini, T.E.Marchant, A.J.Martin, J.P.Martin, G.Martinez, T.Mashimo, P.Mättig, W.J.McDonald, J.McKenna, E.A.Mckigney , T.J.McMahon, R.A.McPherson, F.Meijers, P.Mendez-Lorenzo, F.S.Merritt, H.Mes, I.Meyer, A.Michelini, S.Mihara, G.Mikenberg, D.J.Miller, W.Mohr, A.Montanari, T.Mori, K.Nagai, I. Nakamura, H.A.Neal, R.Nisius, S.W.O’Neale, F.G.Oakham, F.Odorici, H.O.Ogren, A.Okpara, M.J.Oreglia, S.Orito, G. Pásztor, J.R. Pater, G.N.Patrick, J. Patt, R. Perez-Ochoa, S. Petzold, P. Pfeifenschneider , J.E. Pilcher, J. Pinfold, D.E. Plane, P. Poffenberger, B. Poli, J. Polok, M.Przybycień, A.Quadt, C.Rembser, H.Rick, S. Robertson, S.A.Robins, N.Rodning, J.M.Roney, S. Rosati, K.Roscoe, A.M.Rossi, Y.Rozen, K.Runge, O.Runolfsson, D.R.Rust, K. Sachs, T. Saeki, O. Sahr, W.M. Sang, E.K.G. Sarkisyan, C. Sbarra, A.D. Schaile, O. Schaile, P. Scharff-Hansen, J. Schieck, S. Schmitt, A. Schöning, M. Schröder, M. Schumacher, C. Schwick, W.G. Scott, R. Seuster, T.G. Shears, B.C. Shen, C.H. Shepherd-Themistocleous , P. Sherwood, G.P. Siroli, A. Skuja, A.M. Smith, G.A. Snow, R. Sobie, S. Söldner-Rembold , S. Spagnolo, M. Sproston, A. Stahl, K. Stephens, K. Stoll, D. Strom, R. Ströhmer, B. Surrow, S.D.Talbot, P.Taras,

A search is conducted for a low-mass charged Higgs boson produced in a top quark decay and subsequently decaying into a charm and a strange quark. The data sample was recorded in proton-proton collisions at $\\sqrt{s}=$ 13 TeV by the CMS experiment at the LHC and corresponds to an integrated luminosity of 35.9 fb$^{-1}$. The search is performed in the process of top quark pair production, where one top quark decays to a bottom quark and a charged Higgs boson, and the other to a bottom quark and a W boson. With the W boson decaying to a charged lepton (electron or muon) and a neutrino, the final state comprises an isolated lepton, missing transverse momentum, and at least four jets, of which two are tagged as b jets. To enhance the search sensitivity, one of the jets originating from the charged Higgs boson is required to satisfy a charm tagging selection. No significant excess beyond standard model predictions is found in the dijet invariant mass distribution. An upper limit in the range 1.68-0.25% is set on the branching fraction of the top quark decay to the charged Higgs boson and bottom quark for a charged Higgs boson mass between 80 and 160 GeV.

We perform the first measurement on the D 0 − ¯ D 0 mixing parameters using a time-dependent amplitude analysis of the decay D 0 → π þ π − π 0 . The data were recorded with the BABAR detector at center-of-mass energies at and near the ϒ ð 4 S Þ resonance, and correspond to an integrated luminosity of approximately 468 . 1 fb − 1 . The neutral D meson candidates are selected from D (cid:2) ð 2010 Þ þ → D 0 π þ s decays where the flavor at the production is identified by the charge of the low-momentum pion, π þ s . The measured mixing parameters are x ¼ ð 1 . 5 (cid:3) 1 . 2 (cid:3) 0 . 6 Þ % and y ¼ ð 0 . 2 (cid:3) 0 . 9 (cid:3) 0 . 5 Þ % , where the quoted uncertainties are statistical and systematic, respectively.

Evidence is presented for the baryonic B meson decay ¯ B 0 → D 0 Λ ¯ Λ based on a data sample of 471 × 10 6 B ¯ B pairs collected with the BABAR detector at the PEP-II asymmetric e þ e − collider located at the SLAC National Accelerator Laboratory. The branching fraction is determined to be B ð ¯ B 0 → D 0 Λ ¯ Λ Þ¼ ð 9 . 8 þ 2 . 9 − 2 . 6 (cid:1) 1 . 9 Þ × 10 − 6 , corresponding to a significance of 3.4 standard deviations including additive systematic uncertainties. A search for the related baryonic B meson decay ¯ B 0 → D 0 Σ 0 ¯ Λ with Σ 0 → Λ γ is performed and an upper limit B ð ¯ B 0 → D 0 Σ 0 ¯ Λ þ ¯ B 0 → D 0 Λ ¯ Σ 0 Þ < 3 . 1 × 10 − 5 is determined at 90% confidence level.

Citation Lees, J. P., V. Poireau, V. Tisserand, E. Grauges, A. Palano, G. Eigen, B. Stugu, et al. “Cross Sections for the Reactions e[superscript +]e[superscript -] K[0 over S]K[0 over L, K[0 over S]K[0 over L][superscript +][superscript -], K[0 over S]K[0 over S][superscript +][superscript -], and K[0 over S]K[0 over S]K[superscript +]K[superscript -] from Events with Initial-State Radiation.” Phys. Rev. D 89, no. 9 (May 2014). © 2014 American Physical Society

M easurem entsofthe lepton polarization and forward-backward polarization asym m etry near the Z resonance using the O PAL detector are described. The m easurem ents are based on analyses of ! e e , ! , ! , ! and ! a1 decays from a sam ple of 144;810 e e ! + candidates corresponding to an integrated lum inosity of 151 pb . Assum ing thatthe lepton decays according to V A theory,we m easure the average polarization near p s = M Z to be hP i = ( 14:10 0:73 0:55)% and the polarization forward-backward asym m etry to be A FB pol = ( 10:55 0:76 0:25)% ,where the rst error isstatisticaland the second system atic. Taking into account the sm alle ects ofthe photon propagator,photon-Z interference and photonic radiative corrections,these results can be expressed in term softhelepton neutralcurrentasym m etry param eters:

for the lepton-number violating processes B + → h − ℓ + ℓ + with h − = K − /π − and ℓ + = e + /µ + , using a sample of 471 ± 3 million BB events collected with the B A B AR detector at the PEP-II e + e − collider at the SLAC National Accelerator Laboratory. We find no evidence for these decays and place 90% confidence level upper limits on their branching fractions B ( B + → π − e + e + ) < 2 . 3 × 10 − 8 , B ( B + → K − e + e + ) < 3 . 0 × 10 − 8 , B ( B + → π − µ + µ + ) < 10 . 7 × 10 − 8 , and B ( B + → K − µ + µ + ) < 6 . 7 × 10 − 8 .

We report the observation of the baryonic B decay (B) over bar (0) -> Lambda(+)(c)Lambda K(-) with a significance larger than 7 standard deviations based on 471 x 10(6) B (B) over bar pairs collected with the BABAR detector at the PEP-II storage ring at SLAC. We measure the branching fraction for the decay (B) over bar (0) -> Lambda(+)(c)Lambda K(-) to be (3.8 +/- 0.8(stat) +/- 0.2(sys) +/- 1.0(Lambda c)(+)) x 10(-5). The uncertainties are statistical, systematic, and due to the uncertainty in the Lambda(+)(c) branching fraction. We find that the Lambda(+)(c)K(-) invariant-mass distribution shows an enhancement above 3.5 GeV/c(2).

We present measurements of B-meson decays to the final states eta'rho, eta'f(0), and eta'K*, where K* stands for a vector, scalar, or tensor strange meson. We observe a significant signal or evidence for eta'rho(+) and all the eta'K* channels. We also measure, where applicable, the charge asymmetries, finding results consistent with no direct CP violation in all cases. The measurements are performed on a data sample consisting of 467 X 10(6) B (B) over bar pairs, collected with the BABAR detector at the PEP-II e(+)e(-) collider at the SLAC National Accelerator Laboratory. Our results favor the theoretical predictions from perturbative QCD and QCD factorization and we observe an enhancement of the tensor K-2*(1430) with respect to the vector K*(892) component.

The absolute branching fractions for the decays D − s → (cid:2) − ¯ ν (cid:2) ( (cid:2) = e , μ , or τ ) are measured using a data sample corresponding to an integrated luminosity of 521 fb − 1 collected at center of mass energies near 10.58 GeV with the B A B AR detector at the PEP-II e + e − collider at SLAC. The number of D − s mesons is determined by reconstructing the recoiling system DKXγ in events of the type e + e − → DKXD ∗− s , where D ∗− s → D − s γ and X represents additional pions from fragmentation. The D − s → (cid:2) − ν (cid:2) events are detected by full or partial reconstruction of the recoiling system DKXγ(cid:2) . The branching fraction measurements are combined to determine the D − s decay constant f D s = (258 . 6 ± 6 . 4 ± 7 . 5) MeV, where the first uncertainty is statistical and the second is systematic.

We present a measurement of the B0 -> Lambda-bar p pi branching fraction performed using the BaBar detector at the PEP-II asymmetric energy e+e- collider. Based on a 232 million BB-bar pairs data sample we measure: BR(B0 -> Lambda-bar p pi) = [ 3.30 +- 0.53 (stat.) +- 0.31(syst.) ] x 10^-6. A measurement of the differential spectrum as a function of the di-baryon invariant mass m(Lambda p) is also presented; this shows a near-threshold enhancement similar to that observed in other baryonic B decays.

We present a Dalitz plot analysis of charmless B (cid:1) decays to the final state (cid:1) (cid:1) (cid:1) (cid:1) (cid:1) (cid:2) using a sample of ð 465 (cid:1) 5 Þ (cid:3) 10 6 B (cid:1) B pairs collected by the BABAR experiment at ffiffiffi s p ¼ 10 : 58 GeV . We measure the branching fractions , Þ Þ ¼ ð 8 : 1 0 : 7 1 : 2 þ : 1 : 1 Þ 6 , B B ! f 2 1270 (cid:1) ¼ : 57 (cid:1) : 42 (cid:1) 0 : 16 : 19 Þ 10 6 , and B ð B ! nonresonant ¼ : : 0 : 6 þ 1 : 1 (cid:4) 0 : 5 Þ (cid:3) 10 (cid:4) 6 , where the uncertainties are statistical, systematic, and model-dependent, respectively. Measurements of branching fractions for the modes B (cid:1) ! (cid:2) 0 ð 1450 Þ (cid:1) (cid:1) and B (cid:1) ! f 0 ð 1370 Þ (cid:1) (cid:1) are also presented. We observe no significant direct CP asymmetries for the above modes, and there is no evidence for the decays B (cid:1) ! f 0 ð 980 Þ (cid:1) (cid:1) , B (cid:1) ! (cid:3) c 0 (cid:1) (cid:1) , or B (cid:1) ! (cid:3) c 2 (cid:1) .