A multicenter evaluation of the efficacy and duration of action of alcaftadine 0.25% and olopatadine 0.2% in the conjunctival allergen challenge model

Background: The purpose of this study was to evaluate the efficacy and duration of action of once-daily dosing with alcaftadine 0.25% ophthalmic solution and olopatadine 0.2% ophthalmic solution as compared with placebo in the prevention of ocular itching, and to directly compare the efficacy of alcaftadine 0.25% with olopatadine 0.2% in the prevention of ocular itching associated with allergic conjunctivitis using the conjunctival allergen challenge model. Methods: Subjects with allergic conjunctivitis (n = 127) were enrolled in a multicenter, double-masked, randomized, active-controlled and placebo-controlled clinical trial. Using the conjunctival allergen challenge model, this study was conducted over the course of approximately 5 weeks. Subjects were randomized into one of three treatment arms: alcaftadine 0.25% ophthalmic solution, olopatadine 0.2% ophthalmic solution, or placebo. Study medications were administered twice over the course of the trial. The primary efficacy measure for the study was ocular itching evaluated by the subject at 3, 5, and 7 minutes post challenge. Secondary endpoints, measured at 7, 15, and 20 minutes post challenge, included conjunctival, ciliary, and episcleral redness, lid swelling, chemosis, and tearing. Duration of action was measured at 16 and 24 hours post-instillation of the study medication at visits 3 and 4, respectively. Results: For the primary measure of ocular itching, both actives, alcaftadine 0.25% and olopatadine 0.2%, were statistically superior to placebo at all three measured time points for both the 16-hour and 24-hour measures (P < 0.0001). Eyes treated with alcaftadine 0.25% had numerically lower mean ocular itching scores than eyes treated with olopatadine 0.2% at every time point, and this difference was statistically significant at the 3-minute time point 16 hours post instillation (P = 0.026). Eyes treated with alcaftadine 0.25% and with olopatadine 0.2% displayed significantly less lid swelling relative to placebo at every time point for the 16-hour and 24-hour post-instillation visits (P < 0.005). Alcaftadine 0.25% was the only active treatment that provided statistically significant relief of chemosis at every time point of the 24-hour post-instillation visit. Conclusion: Both the alcaftadine 0.25% and olopatadine 0.2% ophthalmic solutions provided highly effective relief of ocular itching at both 16 and 24 hours post-instillation. Treatment differences between the actives were most pronounced at the earliest time point (3 minutes post-challenge) following conjunctival allergen challenge (16 hours), when alcaftadine 0.25% ophthalmic solution was statistically superior to olopatadine 0.2% ophthalmic solution. Alcaftadine 0.25% was the only treatment to provide significant relief from chemosis at both 16 and 24 hours post-instillation. Both active treatments and placebo were generally safe and well tolerated

The Fractured Imaginary: Popular Thinking on Citizen Soldiers and Warfare in Fifth Century Athens

This dissertation establishes how different citizen soldiers were employed and evaluated in the imaginary of fifth century Athens and gives explanations why popular thinking on military personnel was organised in this way. In so doing it emerges that a particular citizen soldier figured in Athenian conceptions about many aspects of martial activity. Also, it has proven necessary to analyse several other conceptions concerning the waging of war in which military personnel strictly play no part because of their indirect but important influence on how this or that class of Athenian fighters was judged. As a result this study ends up throwing light on the ways in which fifth century Athenians conceived not only of citizen combatants but also of warfare in general. The dissertation begins by outlining the primary sources for the Athenian imaginary and its major characteristics. The numerous tragedies and comedies surviving from the fifth century are shown to be sure evidence for the imaginary and the funeral oration of the period to have had a vital role in the transmission of key elements of Athenian self-identity and their understanding of warfare. Although playwrights and public speakers were invariably members of the Athenian elite, the particular contexts in which they performed compelled them to take up and articulate the values and conceptions of their overwhelmingly non-elite audiences. The imaginary then had a decidedly popular character. It was also a sprawling cultural melange within which incongruous and even patently contradictory ideas could subsist side by side. The second part of this dissertation exposes that the citizen hoplite enjoyed a central and paradigmatic role in the popular thinking of fifth century Athens. It was only ever to the heavily armed soldier that poets and orators turned when they wanted to consider general aspects of warfare, the military obligations of citizenship, and gallant and fainthearted behaviour on the battlefield. The Athenian hoplite also served as the pivotal reference point for the marking out of age and gender distinctions within the city and of the differences in military morality between Greeks and barbarians. Critically, as the prevailing definitions of bravery and cowardice were modelled exclusively on the phalanx warfare of the hoplites, Athenian lightly armed troops, cavalrymen and perhaps even sailors with their very different modes of combat were judged one way or another to be cowardly. Yet the final part of this dissertation demonstrates that this normative status of the heavy infantryman in no way prevented citizen sailors from gaining recognition and positive evaluation of their metier and themselves in the Athenian imaginary of the fifth century. The citizen masses of this period saw their city as the major seapower in the Mediterranean and well understood that its formidable might and security rested on its navy. Fifth century Athenians also had a high regard of seamanship in general and great pride in the naval dominance of their city in particular. Indeed, superlative nautical skills were thought to be 'national' traits of the citizens of imperial Athens which they had enjoyed even in the esteemed age of the heroes. Contemporary citizen sailors themselves were also held to be the saviours of the city and were accorded extraordinary esteem and an exalted status if they perished at sea fighting for Athens. Finally, despite the fact that it directly contradicted their hoplite centred conception of bravery, fifth century Athenians firmly believed that fellow citizens serving as sailors could display gallantry in battle

Gauged flavour symmetry for the light generations

We study the phenomenology of a model where an SU(2)^3 flavour symmetry acting on the first two generation quarks is gauged and Yukawa couplings for the light generations are generated by a see-saw mechanism involving heavy fermions needed to cancel flavour-gauge anomalies. We find that, in constrast to the SU(3)^3 case studied in the literature, most of the constraints related to the third generation, like electroweak precision bounds or B physics observables, can be evaded, while characteristic collider signatures are predicted.Comment: 16 pages, 3 figure

Flavour physics from an approximate U(2)^3 symmetry

The quark sector of the Standard Model exhibits an approximate U(2)^3 flavour symmetry. This symmetry, broken in specific directions dictated by minimality, can explain the success of the Cabibbo-Kobayashi-Maskawa picture of flavour mixing and CP violation, confirmed by the data so far, while allowing for observable deviations from it, as expected in most models of ElectroWeak Symmetry Breaking. Building on previous work in the specific context of supersymmetry, we analyze the expected effects and we quantify the current bounds in a general Effective Field Theory framework. As a further relevant example we then show how the U(2)^3 symmetry and its breaking can be implemented in a generic composite Higgs model and we make a first analysis of its peculiar consequences. We also discuss how some partial extension of U(2)^3 to the lepton sector can arise, both in general and in composite Higgs models. An optimistic though conceivable interpretation of the considerations developed in this paper gives reasons to think that new physics searches in the flavour sector may be about to explore an interesting realm of phenomena.Comment: 29 pages, 5 figure

Model-independent constraints on new physics in b --> s transitions

We provide a comprehensive model-independent analysis of rare decays involving the b --> s transition to put constraints on dimension-six Delta(F)=1 effective operators. The constraints are derived from all the available up-to-date experimental data from the B-factories, CDF and LHCb. The implications and future prospects for observables in b --> s l+l- and b --> s nu nu transitions in view of improved measurements are also investigated. The present work updates and generalises previous studies providing, at the same time, a useful tool to test the flavour structure of any theory beyond the SM.Comment: 1+39 pages, 12 figures, 3 tables. v2: minor modifications, typos corrected, references added, version to be published in JHE

Yukawa Unification and the Superpartner Mass Scale

Naturalness in supersymmetry (SUSY) is under siege by increasingly stringent LHC constraints, but natural electroweak symmetry breaking still remains the most powerful motivation for superpartner masses within experimental reach. If naturalness is the wrong criterion then what determines the mass scale of the superpartners? We motivate supersymmetry by (1) gauge coupling unification, (2) dark matter, and (3) precision b-tau Yukawa unification. We show that for an LSP that is a bino-Higgsino admixture, these three requirements lead to an upper-bound on the stop and sbottom masses in the several TeV regime because the threshold correction to the bottom mass at the superpartner scale is required to have a particular size. For tan beta about 50, which is needed for t-b-tau unification, the stops must be lighter than 2.8 TeV when A_t has the opposite sign of the gluino mass, as is favored by renormalization group scaling. For lower values of tan beta, the top and bottom squarks must be even lighter. Yukawa unification plus dark matter implies that superpartners are likely in reach of the LHC, after the upgrade to 14 (or 13) TeV, independent of any considerations of naturalness. We present a model-independent, bottom-up analysis of the SUSY parameter space that is simultaneously consistent with Yukawa unification and the hint for m_h = 125 GeV. We study the flavor and dark matter phenomenology that accompanies this Yukawa unification. A large portion of the parameter space predicts that the branching fraction for B_s to mu^+ mu^- will be observed to be significantly lower than the SM value.Comment: 34 pages plus appendices, 20 figure

Rank-one flavor violation and B-meson anomalies

We assume that the quark-flavor coefficients matrix of the semileptonic operators addressing the neutral-current B-meson anomalies has rank-one, i.e. it can be described by a single vector in quark-flavor space. By correlating the observed anomalies to other flavor and high-pT observables, we constrain its possible directions and we show that a large region of the parameter space of this framework will be explored by flavor data from the NA62, KOTO, LHCb and Belle II experiments

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Observation of associated production of a ZZ boson with a DD meson in the~forward region

A search for associated production of a $Z$ boson with an open charm meson is presented using a data sample, corresponding to an integrated luminosity of $1.0\,\mathrm{fb}^{-`}$ of proton--proton collisions at a centre-of-mass energy of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for associated production of a $Z$ boson with a $D^0$ meson and four candidate events for a $Z$ boson with a $D^+$ meson are observed with a combined significance of 5.1standard deviations. The production cross-sections in the forward region are measured to be $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^0} = 2.50\pm1.12\pm0.22pb$$ $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^+} = 0.44\pm0.23\pm0.03pb,$$ where the first uncertainty is statistical and the second systematic.Comment: 18 pages, 2 figure

Measurements of the B+B^+, B0B^0, Bs0B_s^0 meson and Λb0\Lambda_b^0 baryon lifetimes

Measurements of $b$-hadron lifetimes are reported using $pp$ collision data, corresponding to an integrated luminosity of 1.0fb$^{-1}$, collected by the LHCb detector at a centre-of-mass energy of $7$Tev. Using the exclusive decays $B^+\to J/\psi K^+$, $B^0\to J/\psi K^*(892)^0$, $B^0\to J/\psi K^0_{\rm S}$, $\Lambda_b^0\to J/\psi \Lambda$ and $B^0_s\to J/\psi \phi$ the average decay times in these modes are measured to be $\tau_{B^+\to J/\psi K^+}$ = $1.637 \pm$ 0.004 $\pm$ 0.003 ps, $\tau_{B^0\to J/\psi K^*(892)^0}$ = $1.524 \pm$ 0.006 $\pm$ 0.004 ps, $\tau_{B^0\to J/\psi K^0_{\rm S}}$ = $1.499 \pm$ 0.013 $\pm$ 0.005 ps, $\tau_{\Lambda_b^0\to J/\psi \Lambda}$ = $1.415 \pm$ 0.027 $\pm$ 0.006 ps and $\tau_{B^0_s\to J/\psi \phi}$ = $1.480 \pm$ 0.011 $\pm$ 0.005 ps, where the first uncertainty is statistical and the second is systematic. These represent the most precise lifetime measurements in these decay modes. In addition, ratios of these lifetimes, and the ratio of the decay-width difference, $\Delta\Gamma_d$, to the average width, $\Gamma_d$, in the $B^0$ system, $\Delta \Gamma_d/\Gamma_d = -0.044 \pm 0.025 \pm 0.011$, are reported. All quantities are found to be consistent with Standard Model expectations.Comment: 28 pages, 4 figures. Updated reference