The efficacy of social role models to increase motivation to obtain vaccination against hepatitis B among men who have sex with men

This study assessed the effects of role models in persuasive messages about risk and social norms to increase motivation to obtain hepatitis B virus (HBV) vaccination in men who have sex with men (MSM). MSM at risk for HBV in The Netherlands (N = 168) were recruited online via a range of websites and were randomly assigned to one of four conditions in a 2 (risk communication: yes and no) × 2 (social norms communication: yes and no) factorial design. In each condition, participants subsequently provided self-completed assessments of their perceived risk of HBV infection, perceived social norms regarding HBV vaccination and their intention to obtain vaccination against HBV. Risk communication and social norms communication that used social role models were effective in significantly increasing men's intention to obtain vaccination against HBV. No additive effect was found for a combined message. Mediation analyses showed that communications influenced intention via perceived risk and social norms. Findings extend previous theorizing and research and show that both role model-based risk communication and social norms communication can be effective in increasing intentions to obtain HBV vaccination in MSM. This knowledge contributes to the development of effective health promotion to increase HBV vaccination in MSM. © The Author 2010

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Spin 3 cubic vertices in a frame-like formalism

Till now most of the results on interaction vertices for massless higher spin fields were obtained in a metric-like formalism using completely symmetric (spin-)tensors. In this, the Lagrangians turn out to be very complicated and the main reason is that the higher the spin one want to consider the more derivatives one has to introduce. In this paper we show that such investigations can be greatly simplified if one works in a frame-like formalism. As an illustration we consider massless spin 3 particle and reconstruct a number of vertices describing its interactions with lower spin 2, 1 and 0 ones. In all cases considered we give explicit expressions for the Lagrangians and gauge transformations and check that the algebra of gauge transformations is indeed closed.Comment: 17 pades, no figure

Munc13 controls the location and efficiency of dense-core vesicle release in neurons

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically

Effective action in a higher-spin background

We consider a free massless scalar field coupled to an infinite tower of background higher-spin gauge fields via minimal coupling to the traceless conserved currents. The set of Abelian gauge transformations is deformed to the non-Abelian group of unitary operators acting on the scalar field. The gauge invariant effective action is computed perturbatively in the external fields. The structure of the various (divergent or finite) terms is determined. In particular, the quadratic part of the logarithmically divergent (or of the finite) term is expressed in terms of curvatures and related to conformal higher-spin gravity. The generalized higher-spin Weyl anomalies are also determined. The relation with the theory of interacting higher-spin gauge fields on anti de Sitter spacetime via the holographic correspondence is discussed.Comment: 40 pages, Some errors and typos corrected, Version published in JHE

(1,0) superconformal models in six dimensions

We construct six-dimensional (1,0) superconformal models with non-abelian gauge couplings for multiple tensor multiplets. A crucial ingredient in the construction is the introduction of three-form gauge potentials which communicate degrees of freedom between the tensor multiplets and the Yang-Mills multiplet, but do not introduce additional degrees of freedom. Generically these models provide only equations of motions. For a subclass also a Lagrangian formulation exists, however it appears to exhibit indefinite metrics in the kinetic sector. We discuss several examples and analyze the excitation spectra in their supersymmetric vacua. In general, the models are perturbatively defined only in the spontaneously broken phase with the vev of the tensor multiplet scalars serving as the inverse coupling constants of the Yang-Mills multiplet. We briefly discuss the inclusion of hypermultiplets which complete the field content to that of superconformal (2,0) theories.Comment: 30 pages, v2: Note, some comments and references adde

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

Higher spin interactions with scalar matter on constant curvature spacetimes: conserved current and cubic coupling generating functions

Cubic couplings between a complex scalar field and a tower of symmetric tensor gauge fields of all ranks are investigated on any constant curvature spacetime of dimension d>2. Following Noether's method, the gauge fields interact with the scalar field via minimal coupling to the conserved currents. A symmetric conserved current, bilinear in the scalar field and containing up to r derivatives, is obtained for any rank r from its flat spacetime counterpart in dimension d+1, via a radial dimensional reduction valid precisely for the mass-square domain of unitarity in (anti) de Sitter spacetime of dimension d. The infinite collection of conserved currents and cubic vertices are summarized in a compact form by making use of generating functions and of the Weyl/Wigner quantization on constant curvature spaces.Comment: 35+1 pages, v2: two references added, typos corrected, enlarged discussions in Subsection 5.2 and in Conclusion, to appear in JHE

Anomalous Dimensions of Non-Chiral Operators from AdS/CFT

Non-chiral operators with positive anomalous dimensions can have interesting applications to supersymmetric model building. Motivated by this, we develop a new method for obtaining the anomalous dimensions of non-chiral double-trace operators in N=1 superconformal field theories (SCFTs) with weakly-coupled AdS duals. Via the Hamiltonian formulation of AdS/CFT, we show how to directly compute the anomalous dimension as a bound state energy in the gravity dual. This simplifies previous approaches based on the four-point function and the OPE. We apply our method to a class of effective AdS5 supergravity models, and we find that the binding energy can have either sign. If such models can be UV completed, they will provide the first calculable examples of SCFTs with positive anomalous dimensions.Comment: 38 pages, 2 figures, refs adde

Universal contributions to scalar masses from five dimensional supergravity

We compute the effective Kahler potential for matter fields in warped compactifications, starting from five dimensional gauged supergravity, as a function of the matter fields localization. We show that truncation to zero modes is inconsistent and the tree-level exchange of the massive gravitational multiplet is needed for consistency of the four-dimensional theory. In addition to the standard Kahler coming from dimensional reduction, we find the quartic correction coming from integrating out the gravity multiplet. We apply our result to the computation of scalar masses, by assuming that the SUSY breaking field is a bulk hypermultiplet. In the limit of extreme opposite localization of the matter and the spurion fields, we find zero scalar masses, consistent with sequestering arguments. Surprisingly enough, for all the other cases the scalar masses are tachyonic. This suggests the holographic interpretation that a CFT sector always generates operators contributing in a tachyonic way to scalar masses. Viability of warped su- persymmetric compactifications necessarily asks then for additional contributions. We discuss the case of additional bulk vector multiplets with mixed boundary conditions, which is a partic- ularly simple and attractive way to generate large positive scalar masses. We show that in this case successful fermion mass matrices implies highly degenerate scalar masses for the first two generations of squarks and sleptons.Comment: 23 pages. v2: References added, new section on effect of additional bulk vector multiplets and phenomenolog