Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study

BACKGROUND: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. METHODS: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m2 on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). RESULTS: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy). CONCLUSIONS: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma

A consistent picture for large penguins in D -> pi+ pi-, K+ K-

A long-standing puzzle in charm physics is the large difference between the D0 -> K+ K- and D0 -> pi+ pi- decay rates. Recently, the LHCb and CDF collaborations reported a surprisingly large difference between the direct CP asymmetries, Delta A_CP, in these two modes. We show that the two puzzles are naturally related in the Standard Model via s- and d-quark "penguin contractions". Their sum gives rise to Delta A_CP, while their difference contributes to the two branching ratios with opposite sign. Assuming nominal SU(3) breaking, a U-spin fit to the D0 -> K+ pi-, pi+ K-, pi+ pi-, K+ K- decay rates yields large penguin contractions that naturally explain Delta A_CP. Expectations for the individual CP asymmetries are also discussed.Comment: 24 pages, 8 figure

Books

Human neurology The Human Central Nervous System: A Synopsis and Atlas. 3rd revised ed. Ed. by R. Nieuwenhuys, J. Voogd, C. H. R. van Huijzen. Pp. xii + 437. Illustrated. DM 85. Berlin: SpringerVerlag. 1988.Paediatric respiratory disorders Kendig's Disorders of the Respiratory Tract in Children. 5th ed. Ed. by Victor Chernick. Consulting ed. Edwin L. Kendig, jun. Pp. xxi + 1055. Philadelphia: WB Saunders. 1990.Maxillofacial imaging Maxillofacial Imaging. Ed. by A. M. Delbalso. pp. Vlll + 799. Illustrated. Kent: Harcourt Brace Jovanovich. 1990.Introduction to philosophy of medicine Philosophy of Medicine: An Introduction. Ed. by H. R. Wulff, S. A. Pedersen and R. Rosenberg. pp. xv + 222. £14,95. Oxford: Blackwell. 1990.Cataract management Management of Cataract in Primary Health Care Services. Pp. vi + 43. Illustrated. SFr. 15. Geneva: WHO. 1990.Family practice-management Family Practice Management. Ed. by G. J. and C. M. 1. Pistorius. Pp. 587. Illustrated. R99,50. Parow: Haurn/De Jager. J99O.Obstetrics and gynaecology Essential Obstetrics and Gynaecology. By E. Malcolm Symonds. pp. vi + 266. Illustrated. Edinburgh: Maskew Miller Longman.Surgical memoirs Surgical Roots and Branches. Ed. by R. Murley. Pp. x + 341. Illustrated. £18,50. Hamilton: Libriger Book Distribution. 1990.Survival in a hostile environment Staying Alive. Ed. by Ron Reid-Daly. Pp. ix + 259. Illustrated. R49,95. Rivonia: Ashami. 1990.Urolithiasis Urolithiasis: Medical and Surgical Reference. Ed. by M. 1. Resnick and C. Y. C. Pak. Pp. x + 375. Illustrated. R53,50. Kent: Harcoun Brace Jovanovich. 1990.Mental health in primary health care The Introduction of a Mental Health Component into Primary Health Care. pp. 1-59. SFr. 11,50. Geneva: WHO. 1990Tuberculosis in South Africa White Plague, Black Labor: Tuberculosis and the Political Economy of Health and Disease in South Africa. Ed. by Randall M. Packard. pp. xxii + 389. Illustrated. $40 (cloth) and$15,95 (paperback). California: University of California Press. 1989.Medical research Research in Medicine:"A Guide to Writing a Thesis in the Medical Sciences. Ed. by G. Murrell, C. Huang and H. Ellis. PP: xii + 105. Illustrated. £19,50 (hIb) £7,50 (Plb). Cambridge: Cambridge University Press. 1990

B-->pi and B-->K transitions in standard and quenched chiral perturbation theory

We study the effects of chiral logs on the heavy-->light pseudoscalar meson transition form factors by using standard and quenched chiral perturbation theory combined with the static heavy quark limit. The resulting expressions are used to indicate the size of uncertainties due to the use of the quenched approximation in the current lattice studies. They may also be used to assess the size of systematic uncertainties induced by missing chiral log terms in extrapolating toward the physical pion mass. We also provide the coefficient multiplying the quenched chiral log, which may be useful if the quenched lattice studies are performed with very light mesons.Comment: 33 pages, 8 PostScript figures, version to appear in PR

Patterns and Collective Behavior in Granular Media: Theoretical Concepts

Granular materials are ubiquitous in our daily lives. While they have been a subject of intensive engineering research for centuries, in the last decade granular matter attracted significant attention of physicists. Yet despite a major efforts by many groups, the theoretical description of granular systems remains largely a plethora of different, often contradicting concepts and approaches. Authors give an overview of various theoretical models emerged in the physics of granular matter, with the focus on the onset of collective behavior and pattern formation. Their aim is two-fold: to identify general principles common for granular systems and other complex non-equilibrium systems, and to elucidate important distinctions between collective behavior in granular and continuum pattern-forming systems.Comment: Submitted to Reviews of Modern Physics. Full text with figures (2Mb pdf) avaliable at http://mti.msd.anl.gov/AransonTsimringReview/aranson_tsimring.pdf Community responce is appreciated. Comments/suggestions send to [email protected]

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F(sub lambda) approximates 1.0 X 10(exp -14) ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy

Coulomb Blockade in a Silicon/Silicon-Germanium Two-Dimensional Electron Gas Quantum Dot

We report the fabrication and electrical characterization of a single electron transistor in a modulation doped silicon/silicon-germanium heterostructure. The quantum dot is fabricated by electron beam lithography and subsequent reactive ion etching. The dot potential and electron density are modified by laterally defined side gates in the plane of the dot. Low temperature measurements show Coulomb blockade with a single electron charging energy of 3.2 meV.Comment: Typos corrected; to appear in Appl. Phys. Let

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F_lambda ~ 1.0E10-14 ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy.Comment: 17 pages, 15 figure

Report of Seminar on Law and Medicine

Reports from the UK/CLE Seminar on Law and Medicine held May 26-28, 1976