Search for Heavy Right-Handed Neutrinos at the LHC and Beyond in the Same-Sign Same-Flavor Leptons Final State

In this study we explore the LHC's Run II potential to the discovery of heavy Majorana neutrinos, with luminosities between $30$ and $3000$ fb$^{-1}$ in the $l^{\pm}l^{\pm}j~j$ final state. Given that there exist many models for neutrino mass generation, even within the Type I seesaw framework, we use a simplified model approach and study two simple extensions to the Standard Model, one with a single heavy Majorana neutrino, singlet under the Standard Model gauge group, and a limiting case of the left-right symmetric model. We then extend the analysis to a future hadron collider running at $100$ TeV center of mass energies. This extrapolation in energy allows us to study the relative importance of the resonant production versus gauge boson fusion processes in the study of Majorana neutrinos at hadron colliders. We analyze and propose different search strategies designed to maximize the discovery potential in either the resonant production or the gauge boson fusion modes

Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BackgroundKetoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.MethodsMen with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs).ResultsThirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment.ConclusionsIn docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy

Donor species complement after liver xenotransplantation: The mechanism of protection from hyperacute rejection

Hamster hearts transplanted into stable rat recipients of hamster livers (OLT rats) were hyperacutely rejected after transfer with unaltered rat antihamster hyperimmune serum (HS). This was followed by immediate liver xenograft rejection in 4 of 5 rats. In contrast, simple heat inactivation of the rat HS resulted in prolonged survival of hamster hearts to 25 days without deterioration effect in the liver xenografts. This effect was species-specific because third-party mouse heart grafts in OLT rats were hyperacutely rejected in minutes if either active or heat inactivated antimouse HS was given. In cytotoxicity experiments, the complement in OLT serum produced weak lysis of hamster lymphocytes, while efficiently doing so with mouse cell targets. Because normal hamster serum caused no lysis at all of hamster target cells, the residual low-grade lysis of OLT serum was possibly being mediated by extrahepatic sources of rat C. In conclusion, the homology of C and target cells represents a mechanism of protection that the liver confers to other organs, and that is most easily seen in xenografts but may be allospecifically operational with allografts as well within the limits of MHC restriction. © 1994 by Williams and Wilkins

Duplications in nomenclature

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62822/1/389539a0.pd