Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial.

Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. gov, Number: NCT03191864

Low Energy Theory for 2 flavors at High Density QCD

We construct the effective Lagrangian describing the low energy excitations for Quantum Chromodynamics with two flavors at high density. The non-linear realization framework is employed to properly construct the low energy effective theory. The light degrees of freedom, as required by 't Hooft anomaly conditions, contain massless fermions which we properly include in the effective Lagrangian. We also provide a discussion of the linearly realized Lagrangian.Comment: 17 pages, RevTeX format, references added. To appear in Phys. Rev.

Effects of Large CP violating phases on g_{\m}-2 in MSSM

Effects of CP violation on the supersymmetric electro-weak correction to the anomalous magnetic moment of the muon are investigated with the most general allowed set of CP violating phases in MSSM. The analysis includes contributions from the chargino and the neutralino exchanges to the muon anomaly. The supersymmetric contributions depend only on specific combinations of CP phases. The independent set of such phases is classified. We analyse the effects of the phases under the EDM constraints and show that large CP violating phases can drastically affect the magnitude of the supersymmetric electro-weak contribution to $a_{\mu}$ and may even affect its overall sign.Comment: 26 pages Latex file including 4 figure

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE. We performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety. The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (P = .0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P < .0001 vs placebo), the EoE-histologic scoring system (HSS) severity score by 68.3% (P < .0001 vs placebo), and the endoscopic reference score by 1.6 (P = .0006 vs placebo). Dupilumab increased esophageal distensibility by 18% vs placebo (P < .0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs 8% in the placebo group) and nasopharyngitis (17% vs 4% in the placebo group). In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated. ClinicalTrials.gov, Number: NCT02379052

Gaugino Mass Nonuniversality and Dark Matter in SUGRA, Strings and D Brane Models

The effects of nonuniversality of gaugino masses on dark matter are examined within supersymmetric grand unification, and in string and D brane models with R parity invariance. In SU(5) unified models nonuniversality in the gaugino sector can be generated via the gauge kinetic energy function which may depend on the 24, 75 and 200 dimensional Higgs representations. We also consider string models which allow for nonuniversality of gaugino masses and D brane models where nonuniversality arises from embeddings of the Standard Model gauge group on five branes and nine branes. It is found that with gaugino mass nonuniversality the range of the LSP mass can be extended much beyond the range allowed in the universal SUGRA case, up to about 600 GeV even without coannihilation effects in some regions of the parameter space. The effects of coannihilation are not considered and inclusion of these effects may further increase the allowed neutralino mass range. Similarly with the inclusion of gaugino mass nonuniversality, the neutralino-proton ($\chi -p$) cross-section can increase by as much as a factor of 10 in some of regions of the parameter space. An analysis of the uncertainties in the quark density content of the nucleon is given and their effects on $\chi -p$ cross-section are discussed. The predictions of our analysis including nonuniversality is compared with the current limits from dark matter detectors and implications for future dark matter searches are discussed.Comment: Revised version, 23 pages, Latex, and 7 figure

Measurement of spin correlation in ttbar production using dilepton final states

We measure the correlation between the spin of the top quark and the spin of the anti-top quark in (ttbar -> W+ W- b bbar -> l+ nu b l- nubar bbar) final states produced in ppbar collisions at a center of mass energy sqrt(s)=1.96 TeV, where l is an electron or muon. The data correspond to an integrated luminosity of 5.4 fb-1 and were collected with the D0 detector at the Fermilab Tevatron collider. The correlation is extracted from the angles of the two leptons in the t and tbar rest frames, yielding a correlation strength C= 0.10^{+0.45}_{-0.45}, in agreement with the NLO QCD prediction within two standard deviations, but also in agreement with the no correlation hypothesis.Comment: 10 pages, 3 figures, submitted to PL

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).

 Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas