1,364 research outputs found
Enhanced CP Violation with Modes and Extraction of the CKM Angle gamma
The Gronau-London-Wyler (GLW) method extracts the CKM angle by
measuring decay rates involving mesons. Since that
method necessitates the interference between two amplitudes that are
significantly different in magnitude, the resulting asymmetries tend to be
small. CP violation can be greatly enhanced for decays to final states that are
common to both D^0 and and that are not CP eigenstates. In
particular, large asymmetries are possible for final states f such that is doubly Cabibbo suppressed while is Cabibbo allowed.
The measurement of interference effects in two such modes allows the extraction
of without prior knowledge of , which
may be difficult to determine due to backgrounds.Comment: 12 pages, LaTeX, no figure
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Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.
BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings
Aquatic biosurvey of the Lovell River on UNH land
We assessed the physical, chemical and biological conditions at two sites along the Lovell River on University of New Hampshire (UNH) -owned conservation land. The discharge was 4.4 m3 s-1 at Site 1 and 5.7 m3 s -1 downstream at Site 2. Canopy coverage ranged from 8-25%. Canopy was dominated by Eastern Hemlock (79-84%). Much of the stream was strewn with large boulders and the substrate consisted of rocks of highly variable sizes ( 3-549 cm dia.). Specific conductivity (22.1-23.3 µS), pH (6.4) and temperature (7.9-8.3 °C) varied little between sites. Macro-invertebrate bio-indices indicated either excellent water quality with no apparent organic pollution (3.0/10) or good water quality with possible slight organic pollution (4.4/10)
Getting beta-alpha without penguins
Oscillation effects in B0 -> Ks D0 and related processes are considered to
determine delta=beta-alpha+pi. We suggest that D0 decays to CP eigenstates used
in concert with inclusive D0 decays provide a powerful method for determining
delta cleanly i.e. without any complication from penguin processes. The CP
asymmetry is expected to be <=40% for D0 decays to non-CP eigenstates and <=80%
for decays to CP eigenstates. This method can lead to a fairly accurate
determination of delta with O(10^8-10^9) B-mesons.Comment: 4 pages 1 figure; Version 2: minor changes; references added; Some
changes in response to Referee Comment
Extracting information on CKM phases, electro-weak penguins and new physics from B --> VV decays
We derive constraints for modes ($V= vector meson) that allow
aquantitative assessment of the contributions from electroweak penguins (EWP)
and/or new physics. Interplay of direct CP with oscillation studies then leads
to the extraction of the angles alpha and gamma, using B--> K* omega rho and
B--> rho omega (phi) respectively, if by using our constraint equations it can
be experimentally demonstrated that color-suppressed EWP are small.Comment: 12 pages, 0 figures; revised and expande
Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study
Abstract
Background
Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.
Methods
In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10–50 mcg/kg) on days 1–5 and 15–19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated.
Results
In phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib.
Conclusion
IL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC.
Trial registration
ClinicalTrials.gov Identifier: NCT0038928
Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions
The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India
Weak Coupling Phase from Decays of Charged B Mesons to and
The theory of violation based on phases in weak couplings in the
Cabibbo-Kobayashi-Maskawa (CKM) matrix requires the phase (in a standard convention) to be nonzero. A measurement of
is proposed based on charged meson decay rates to ,
, , and the charge-conjugate states. The corresponding
branching ratios are expected to be of the order of . (submitted to
Physical Review Letters)Comment: LaTeX, 8 pages, 2 figures (not included, available upon request),
TECHNION-PH-94-7, EFI-94-14, UdeM-LPN-TH-94-19
Seeing two faces together: preference formation in humans and rhesus macaques
Humans, great apes and old world monkeys show selective attention to faces depending on conspecificity, familiarity, and social status supporting the view that primates share similar face processing mechanisms. Although many studies have been done on face scanning strategy in monkeys and humans, the mechanisms influencing viewing preference have received little attention. To determine how face categories influence viewing preference in humans and rhesus macaques (Macaca mulatta), we performed two eye-tracking experiments using a visual preference task whereby pairs of faces from different species were presented simultaneously. The results indicated that viewing time was significantly influenced by the pairing of the face categories. Humans showed a strong bias towards an own-race face in an Asian–Caucasian condition. Rhesus macaques directed more attention towards non-human primate faces when they were paired with human faces, regardless of the species. When rhesus faces were paired with faces from Barbary macaques
(Macaca sylvanus) or chimpanzees (Pan troglodytes), the novel species’ faces attracted more attention. These results
indicate that monkeys’ viewing preferences, as assessed by a visual preference task, are modulated by several factors,
species and dominance being the most influential
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