Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with ...HCC and CP class B.
A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19–21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.
Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar.
Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.
A future circular collider (FCC) with a center-of-mass energy of 100 TeV and a circumference of around 100 km, or an energy upgrade of the LHC (HE-LHC) to 27 TeV require bending magnets providing 16 ...T in a 50-mm aperture. Several development programs for these magnets, based on Nb 3 Sn technology, are being pursued in Europe and in the U.S. In these programs, cos-theta, block-type, common-coil, and canted-cos-theta magnets are explored; first model magnets are under manufacture; limits on conductor stress levels are studied; and a conductor with enhanced characteristics is developed. This paper summarizes and discusses the status, plans, and preliminary results of these programs.
This study is based upon a stratigraphic and structural revision of a Middle Jurassic–Upper Cretaceous mostly continental succession exposed between Boumalne Dades and Tinghir (Southern Morocco), and ...aims at reconstructing the relation among sedimentary, tectonic and magmatic processes that affected a portion of the Central High Atlas domains. Basalts interbedded in the continental deposits have been sampled in the two studied sites for petrographic, geochemical and radiogenic isotope analyses. The results of this study provide: (1) a robust support to the local stratigraphic revision and to a regional lithostratigraphic correlation based on new
40
Ar–
39
Ar ages (ca. 120 Ma) of the intervening basalts; (2) clues for reconstructing the relation between magma emplacement in a structural setting characterized by syn-depositional crustal shortening pre-dating the convergent tectonic inversion of the Atlasic rifted basins; (3) a new and intriguing scenario indicating that the Middle Jurassic–Lower Cretaceous basalts of the Central High Atlas could represent the first signal of the present-day Canary Islands mantle plume impinging, flattening, and delaminating the base of the Moroccan continental lithosphere since the Jurassic, and successively dragged passively by the Africa plate motion to NE. The tectono-sedimentary and magmatic events discussed in this paper are preliminarily extended from their local scale into a peculiar geodynamic setting of a continental plate margin flanked by the opening and spreading Central Atlantic and NW Tethys oceans. It is suggested that during the late Mesozoic this setting created an unprecedented condition of intraplate stress for concurrent crustal shortening, related mountain uplift, and thinning of continental lithosphere.
Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes ...untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.
The ISOLDE Scientific Infrastructure at CERN offers a unique range of post-accelerated radioactive beams. The scientific program can be improved with the “Isolde Superconducting Recoil Separator” ...(ISRS), an innovative spectrometer able to deliver unprecedented (A, Z) resolution. In this paper we present an overview of the physics and ongoing technical developments.
The stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism
. The uniquely arched morphology of the human midfoot is thought to ...stiffen it
, whereas other primates have flat feet that bend severely in the midfoot
. However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics
, podiatry
and palaeontology
. These debates centre on the medial longitudinal arch
and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot
. Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion.
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