To serve and protect: Enzyme inhibitors as radiopeptide escorts promote tumor targeting

Radiolabeled octreotide analogs are most successfully being applied today in clinical cancer imaging and treatment. Propagation of this paradigm to other radiopeptide families has been greatly hampered by the inherent poor metabolic stability of systemically administered peptide analogs. We hypothesized that the in vivo coadministration of specific enzyme inhibitors would improve peptide bioavailability and hence tumor uptake. Through single coinjection of the neutral endopeptidase inhibitor phosphoramidon (PA), we were able to provoke remarkable rises in the percentages of circulating intact somatostatin, gastrin, and bombesin radiopeptides in mouse models, resulting in a remarkable increase in uptake in tumor xenografts in mice. Methods: The peptide conjugates [DOTA-Ala1]SS14 (DOTA-Ala-Gly-c[Cys-Lys- Asn-Phe-Phe-Trp-Lys-Thr-Phe- Thr-Ser-Cys]-OH), PanSB1 (DOTAPEG2- DTyr-Gln-Trp-Ala-Val-βAla- His-Phe-Nle-NH2), and DOTA-MG11 (DOTA-DGlu-Al

Multiple Parton Interactions, top--antitop and W+4j production at the LHC

The expected rate for Multiple Parton Interactions (MPI) at the LHC is large. This requires an estimate of their impact on all measurement foreseen at the LHC while opening unprecendented opportunities for a detailed study of these phenomena. In this paper we examine the MPI background to top-antitop production, in the semileptonic channel, in the early phase of data taking when the full power of $b$--tagging will not be available. The MPI background turns out to be small but non negligible, of the order of 20% of the background provided by W+4j production through a Single Parton Interaction. We then analyze the possibility of studying Multiple Parton Interactions in the W+4j channel, a far more complicated setting than the reactions examined at lower energies. The MPI contribution turns out to be dominated by final states with two energetic jets which balance in transverse momentum, and it appears possible, thanks to the good angular resolution of ATLAS and CMS, to separate the Multiple Parton Interactions contribution from Single Parton Interaction processes. The large cross section for two jet production suggests that also Triple Parton Interactions (TPI) could provide a non negligible contribution. Our preliminary analysis suggests that it might be indeed possible to investigate TPI at the LHC.Comment: Typos fixed. Published in JHE

NNLO corrections to event shapes in e+e−e^+e^- annihilation

We compute the next-to-next-to-leading order (NNLO) QCD corrections to the six most important event shape variables related to three-particle final states in electron-positron annihilation. The corrections are sizeable for all variables, however their magnitude is substantially different for different observables. We observe that the NNLO corrections yield a considerably better agreement between theory and experimental data both in shape and normalisation of the event shape distributions. The renormalisation scale dependence of the theoretical prediction is substantially reduced compared to the previously existing NLO results. Our results will allow a precise determination of the strong coupling constant from event shape data collected at LEP.Comment: 30 pages, LaTeX, numercial results corrected for oversubtraction of large-angle soft radiatio

Boson-boson scattering and Higgs production at the LHC from a six fermion point of view: four jets + lν\nu processes at \O(\alpha_{em}^6)

Boson-boson scattering and Higgs production in boson-boson fusion hold the key to electroweak symmetry breaking. In order to analyze these essential features of the Standard Model we have performed a partonic level study of all processes $q_1 q_2 \to q_3 q_4 q_5 q_6 l \nu$ at the LHC using the exact matrix elements at \O(\alpha_{em}^6) provided by \Phase, a new MC generator. These processes include also three boson production and the purely electroweak contribution to \toptop production as well as all irreducible backgrounds. Kinematical cuts have been studied in order to enhance the VV scattering signal over background. \Phase has been compared with different Monte Carlo's showing that a complete calculation is necessary for a correct description of the process.Comment: 26 pages, 19 figure

Multiple Parton Interactions in Z+jets production at the LHC. A comparison of factorized and non--factorized double parton distribution functions

We examine the contribution of Multiple Parton Interactions to Z+n-jets production at the LHC, n=2,3,4, where the Z boson is assumed to decay leptonically. We compare the results obtained with the correlated GS09 double parton distribution function with those obtained with two instances of fully factorized single parton distribution functions: MSTW2008LO and CTEQ6LO. It appears quite feasible to measure the MPI contribution to Z+2/3/4 jets already in the first phase of the LHC with a total luminosity of one inverse femtobarn at 7 TeV. If as expected the trigger threshold for single photons is around 80 GeV, Z+2-jets production may well turn out to be more easily observable than the gamma+3-jets channel. The MPI cross section is dominated by relatively soft events with two jets balancing in transverse momentum.Comment: 15 pages, 3 plot

Logarithmic electroweak corrections to gauge-boson pair production at the LHC

We have studied the effects of the complete logarithmic electroweak O(alpha) corrections on the production of vector-boson pairs WZ, ZZ, and WW at the LHC. These corrections are implemented into a Monte Carlo program for pp -> 4f (+\gamma) with final states involving four or two leptons using the double-pole approximation. We numerically investigate purely leptonic final states and find that electroweak corrections lower the predictions by 5-30% in the physically interesting region of large di-boson invariant mass and large angle of the produced vector bosons.Comment: 47 pages, LaTeX, 18 eps figure

Same-sign W pair production as a probe of double parton scattering at the LHC

We study the production of same-sign W boson pairs at the LHC in double parton interactions. Compared with simple factorised double parton distributions (dPDFs), we show that the recently developed dPDFs, GS09, lead to non-trivial kinematic correlations between the W bosons. A numerical study of the prospects for observing this process using same-sign dilepton signatures, including same-sign WWjj, di-boson and heavy flavour backgrounds, at 14 TeV centre-of-mass energy is then performed. It is shown that a small excess of same-sign dilepton events from double parton scattering over a background dominated by single scattering WZ(gamma*) production could be observed at the LHC.Comment: 14 pages, 8 figures. Added references, slight changes in the text

PHASE, a Monte Carlo event generator for six-fermion physics at the LHC

PHASE is a new event generator dedicated to the study of Standard Model processes with six fermions in the final state at the LHC. The code is intended for analyses of vector boson scattering, Higgs search, three gauge boson production, and top physics. This first version of the program describes final states characterized by the presence of one neutrino, $pp\to 4q +l\nu_l$, at O($\alpha^6$). PHASE is based on a new iterative-adaptive multichannel technique, and employs exact leading order matrix elements. The code can generate unweighted events for any subset of all available final states. The produced parton-level events carry full information on their colour and flavour structure, enabling the evolution of the partons into fully hadronised final states. An interface to hadronization packages is provided via the Les Houches Protocol.Comment: 27 pages, Latex, 6 figure

Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly affecting people with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the effect of fluorouracil 1% eye drops after surgery on recurrence. METHODS: We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly allocated to receive either topical fluorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratified by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month, 3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with Pan-African Clinical Trials Registry (PACTR201207000396219). FINDINGS: Between August, 2012, and July, 2014, we assigned 49 participants to fluorouracil and 49 to placebo. Four participants were lost to follow-up. Recurrences occurred in five (11%) of 47 patients in the fluorouracil group and 17 (36%) of 47 in the placebo group (odds ratio 0·21, 95% CI 0·07–0·63; p=0·01). Adjusting for passive smoking and antiretroviral therapy had little effect (odds ratio 0·23; 95% CI 0·07–0·75; p=0·02). Adverse effects occurred more commonly in the fluorouracil group, although they were transient and mild. Ocular discomfort occurred in 43 of 49 patients in the fluorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus five, and eyelid skin inflammation occurred in seven versus none. INTERPRETATION: Topical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended