Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease.</p> <p>A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy.</p> <p>Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer.</p> <p>Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer.</p> <p>Design</p> <p>This is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01294358">NCT01294358</a></p

The Aguablanca Ni–(Cu) sulfide deposit, SW Spain: geologic and geochemical controls and the relationship with a midcrustal layered mafic complex

The Aguablanca Ni–(Cu) sulfide deposit is hosted by a breccia pipe within a gabbro–diorite pluton. The deposit probably formed due to the disruption of a partially crystallized layered mafic complex at about 12– 19 km depth and the subsequent emplacement of melts and breccias at shallow levels (<2 km). The ore-hosting breccias are interpreted as fragments of an ultramafic cumulate, which were transported to the near surface along with a molten sulfide melt. Phlogopite Ar–Ar ages are 341– 332 Ma in the breccia pipe, and 338–334 Ma in the layered mafic complex, and are similar to recently reported U–Pb ages of the host Aguablanca Stock and other nearby calcalkaline metaluminous intrusions (ca. 350–330 Ma). Ore deposition resulted from the combination of two critical factors, the emplacement of a layered mafic complex deep in the continental crust and the development of small dilational structures along transcrustal strike-slip faults that triggered the forceful intrusion of magmas to shallow levels. The emplacement of basaltic magmas in the lower middle crust was accompanied by major interaction with the host rocks, immiscibility of a sulfide melt, and the formation of a magma chamber with ultramafic cumulates and sulfide melt at the bottom and a vertically zoned mafic to intermediate magmas above. Dismembered bodies of mafic/ultramafic rocks thought to be parts of the complex crop out about 50 km southwest of the deposit in a tectonically uplifted block (Cortegana Igneous Complex, Aracena Massif). Reactivation of Variscan structures that merged at the depth of the mafic complex led to sequential extraction of melts, cumulates, and sulfide magma. Lithogeochemistry and Sr and Nd isotope data of the Aguablanca Stock reflect the mixing from two distinct reservoirs, i.e., an evolved siliciclastic middle-upper continental crust and a primitive tholeiitic melt. Crustal contamination in the deep magma chamber was so intense that orthopyroxene replaced olivine as the main mineral phase controlling the early fractional crystallization of the melt. Geochemical evidence includes enrichment in SiO2 and incompatible elements, and Sr and Nd isotope compositions (87Sr/86Sri 0.708–0.710; 143Nd/144Ndi 0.512–0.513). However, rocks of the Cortegana Igneous Complex have low initial 87Sr/86Sr and high initial 143Nd/144Nd values suggesting contamination by lower crustal rocks. Comparison of the geochemical and geological features of igneous rocks in the Aguablanca deposit and the Cortegana Igneous Complex indicates that, although probably part of the same magmatic system, they are rather different and the rocks of the Cortegana Igneous Complex were not the direct source of the Aguablanca deposit. Crust–magma interaction was a complex process, and the generation of orebodies was controlled by local but highly variable factors. The model for the formation of the Aguablanca deposit presented in this study implies that dense sulfide melts can effectively travel long distances through the continental crust and that dilational zones within compressional belts can effectively focus such melt transport into shallow environments

Forecasting Daily Variability of the S and P 100 Stock Index using Historical, Realised and Implied Volatility Measurements

The increasing availability of financial market data at intraday frequencies has not only led to the development of improved volatility measurements but has also inspired research into their potential value as an information source for volatility forecasting. In this paper we explore the forecasting value of historical volatility (extracted from daily return series), of implied volatility (extracted from option pricing data) and of realised volatility (computed as the sum of squared high frequency returns within a day). First we consider unobserved components and long memory models for realised volatility which is regarded as an accurate estimator of volatility. The predictive abilities of realised volatility models are compared with those of stochastic volatility models and generalised autoregressive conditional heteroskedasticity models for daily return series. These historical volatility models are extended to include realised and implied volatility measures as explanatory variables for volatility. The main focus is on forecasting the daily variability of the Standard and Poor's 100 stock index series for which trading data (tick by tick) of almost seven years is analysed. The forecast assessment is based on the hypothesis of whether a forecast model is outperformed by alternative models. In particular, we will use superior predictive ability tests to investigate the relative forecast performances of some models. Since volatilities are not observed, realised volatility is taken as a proxy for actual volatility and is used for computing the forecast error. A stationary bootstrap procedure is required for computing the test statistic and its $p$-value. The empirical results show convincingly that realised volatility models produce far more accurate volatility forecasts compared to models based on daily returns. Long memory models seem to provide the most accurate forecasts

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Search for the standard model Higgs boson produced in association with a top-quark pair in pp collisions at the LHC

This is the pre-print version of the final published paper that is available from the link below.A search for the standard model Higgs boson produced in association with a top-quark pair is presented using data samples corresponding to an integrated luminosity of 5.0 fb-1 (5.1 fb-1) collected in pp collisions at the center-of-mass energy of 7TeV (8TeV). Events are considered where the top-quark pair decays to either one lepton+jets (tt→lvqq’bb) or dileptons [tt→l(+)vl(-)vbb], l being an electron or a muon. The search is optimized for the decay mode H → bb. The largest background to the ttH signal is top-quark pair production with additional jets. Artificial neural networks are used to discriminate between signal and background events. Combining the results from the 7TeV and 8TeV samples, the observed (expected) limit on the cross section for Higgs boson production in association with top quark pairs for a Higgs boson mass of 125 GeV is 5.8 (5.2) times the standard model expectatio

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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