Episodic Nonlinearity in Leading Global Currencies

We perform non-linearity tests using daily data for leading currencies that include the Australian dollar, British pound, Brazilian real, Canadian dollar, euro, Japanese yen, Mexican peso, and the Swiss franc to resolve the issue of whether these currencies are driven by fundamentals or exogenous shocks to the global economy. In particular, we use a new method of testing for linear and nonlinear lead/lag relationships between time series, introduced by Brooks and Hinich (1999), based on the concepts of cross-correlation and crossbicorrelation. Our evidence points to a relatively rare episodic nonlinearity within and across foreign exchange rates. We also test the validity of specifying ARCH-type error structures for foreign exchange rates. In doing so, we estimate Bollerslevs (1986) generalized ARCH (GARCH) model and Nelsons (1988) exponential GARCH (EGARCH) model, using a variety of error densities [including the normal, the Student-t distribution, and the Generalized Error Distribution (GED)] and a comprehensive set of diagnostic checks. We apply the Brooks and Hinich (1999) nonlinearity test to the standardized residuals of the optimal GARCH/EGARCH model for each exchange rate series and show that the nonlinearity in the exchange rates is not due to ARCH-type e⁄ects. This result has important implications for the interpretation of the recent voluminous literature which attempts to model nancial asset returns using this family of models

Cystic Dilatations of the Common Bile Duct in Adults

Cystic dilatations of the common bile duct are believed to be of congenital etiology with most cases presenting in childhood. During the last 20 years, 10 patients with cystic dilatations of the bile duct were treated in our Department. There were 5 men and 5 women with an age range of 35–81 years. Clinical presentation consisted of right hypohondrial pain, nausea, vomiting and a history of obstructive jaundice. Diagnosis was established by ultrasound, cholangiography and ERCP in most cases. According to the Todani classification system, 5 patients had type I cysts, 4 had type II and one had type III. At the time of surgery, main associated diseases were choledocholithiasis in 3 cases and cholangitis in 2 cases. One patient (type III) underwent endoscopic sphincterotomy; 4 patients underwent internal drainage and 2 of them developed mild cholangitis postoperatively; 5 patients underwent excision of the cyst and a biliary-enteric bypass and developed no main complications. Patients remained in good health during long-term follow-up. We conclude that cyst excision is the treatment ofchoice for adults in order to reduce postoperative morbidity and the potential risk of malignancy

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Application of advanced reservoir characterization, simulation and production optimization strategies to maximize recovery in slope and basin clastic reservoirs, West Texas (Delaware Basin). Annual report

The objective of this project is to demonstrate that detailed reservoir characterization of slope and basin clastic reservoirs in sandstones of the Delaware Mountain Group in the Delaware Basin of West Texas and New Mexico is a cost-effective way to recover a higher percentage of the original oil in place through strategic placement of infill wells and geologically based field development. This project involves reservoir characterization of two Late Permian slope and basin clastic reservoirs in the Delaware Basin, West Texas, followed by a field demonstration in one of the fields. The fields being investigated are Geraldine Ford and Ford West fields in Reeves and Culberson Counties, Texas. Project objectives are divided into two major phases, reservoir characterization and implementation. The objectives of the reservoir characterization phase of the project were to provide a detailed understanding of the architecture and heterogeneity of the two fields, the Ford Geraldine unit and Ford West field. Reservoir characterization utilized 3-D seismic data, high-resolution sequence stratigraphy, subsurface field studies, outcrop characterization, and other techniques. Once reservoir characterized was completed, a pilot area of approximately 1 mi{sup 2} at the northern end of the Ford Geraldine unit was chosen for reservoir simulation. This report summarizes the results of the second year of reservoir characterization

Geologic and engineering characterization of Geraldine Ford field, Reeves and Culberson Counties, Texas. Topical report -- 1997

The objective of this Class III project is to demonstrate that detailed reservoir characterization of clastic reservoirs in basinal sandstones of the Delaware Mountain Group in the Delaware Basin of West Texas and New Mexico is a cost-effective way to recover more of the original oil in place by strategic infill-well placement and geologically based field development. The study focused on Geraldine Ford field, which produces from the upper Bell Canyon formation (Ramsey sandstone). Petrophysical characterization of the Ford Geraldine unit was accomplished by integrating core and log data and quantifying petrophysical properties from wireline logs. The petrophysical data were used to map porosity, permeability, net pay, water saturation, mobile oil saturation, and other reservoir properties. Once the reservoir-characterization study was completed, a demonstration area of approximately 1 mi{sup 2} in the northern part of the unit was chosen for reservoir modeling/simulation. A quarter of a five-spot injection pattern in the demonstration area was selected for flow simulations, and two cases of permeability distribution were considered, one using stochastic permeability distribution generated by conditional simulation and the other using layered permeabilities. Flow simulations were performed using UTCOMP, an isothermal, three-dimensional, compositional simulator for miscible gas flooding. Results indicate that 10--30% (1 to 3 MMbbl) of remaining oil in place in the demonstration area can be produced by CO{sub 2} injection

Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial

PURPOSE In COLUMBUS part 1, patients with advanced BRAF$^{V600}$-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms. METHODS In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety. RESULTS Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2  months (7.4 to 11.1) for ENCO300 (parts 1  and  2) and 7.4  months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1  and  2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1  and  2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300. CONCLUSION COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety

Adjuvant nivolumab for stage III/IV melanoma: Evaluation of safety outcomes and association with recurrence-free survival

Background Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit €'risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Methods Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. Results From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Conclusion Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. Trial registration number NCT02388906