Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study

PURPOSE: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC). PATIENTS AND METHODS: Eligible OC patients had measurable (RECIST1.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response. RESULTS: 150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (<6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash. CONCLUSION: The combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone

Characterization of Filtration Scale-Up Performance

The scale-up performance of sintered stainless steel crossflow filter elements planned for use at the Pretreatment Engineering Platform (PEP) and at the Waste Treatment and Immobilization Plant (WTP) were characterized in partial fulfillment (see Table S.1) of the requirements of Test Plan TP RPP WTP 509. This test report details the results of experimental activities related only to filter scale-up characterization. These tests were performed under the Simulant Testing Program supporting Phase 1 of the demonstration of the pretreatment leaching processes at PEP. Pacific Northwest National Laboratory (PNNL) conducted the tests discussed herein for Bechtel National, Inc. (BNI) to address the data needs of Test Specification 24590-WTP-TSP-RT-07-004. Scale-up characterization tests employ high-level waste (HLW) simulants developed under the Test Plan TP-RPP-WTP-469. The experimental activities outlined in TP-RPP-WTP-509 examined specific processes from two broad areas of simulant behavior: 1) leaching performance of the boehmite simulant as a function of suspending phase chemistry and 2) filtration performance of the blended simulant with respect to filter scale-up and fouling. With regard to leaching behavior, the effect of anions on the kinetics of boehmite leaching was examined. Two experiments were conducted: 1) one examined the effect of the aluminate anion on the rate of boehmite dissolution and 2) another determined the effect of secondary anions typical of Hanford tank wastes on the rate of boehmite dissolution. Both experiments provide insight into how compositional variations in the suspending phase impact the effectiveness of the leaching processes. In addition, the aluminate anion studies provide information on the consequences of gibbsite in waste. The latter derives from the expected fast dissolution of gibbsite relative to boehmite. This test report concerns only results of the filtration performance with respect to scale-up. Test results for boehmite dissolution kinetics and filter fouling are reported elsewhere (see Table S.1). The primary goal of scale-up testing was to examine how filter length influenced permeate flux rates. To accomplish this, the existing cells unit filter system, which employs a 2-ft-long, 0.5-in. (inner) diameter sintered stainless steel filter element, was redesigned to accommodate an 8-ft. sintered stainless steel filter element of the same diameter. Testing was then performed to evaluate the filtration performance of waste simulant slurries. Scale-up testing consisted of two separate series of filtration tests: 1) scale-up axial velocity (AV)/transmembrane pressure (TMP) matrix tests and 2) scale-up temperature tests. The AV/TMP matrix tests examined filtration performance of two different waste simulant slurries in the 8-ft. cells unit filter system. Waste simulant slurry formulations for the 8-ft. scale-up test was selected to match simulant slurries for which filtration performance had been characterized on the 2-ft CUF. For the scale-up temperature tests, the filtration performance at three test temperatures (i.e., 25°C, 40°C, and 60°C) was determined to evaluate if filter flux versus temperature correlations developed using the 2-ft filters were also valid for the 8-ft filters

Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481]

BACKGROUND: Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments. METHOD AND DESIGN: Two hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy. We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline. Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes. DISCUSSION: We have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes

Deposition Velocities of Non-Newtonian Slurries in Pipelines: Complex Simulant Testing

One of the concerns expressed by the External Flowsheet Review Team (EFRT) is about the potential for pipe plugging at the Waste Treatment and Immobilization Plant (WTP). Per the review’s executive summary, “Piping that transports slurries will plug unless it is properly designed to minimize this risk. This design approach has not been followed consistently, which will lead to frequent shutdowns due to line plugging.” To evaluate the potential for plugging, deposition-velocity tests were performed on several physical simulants to determine whether the design approach is conservative. Deposition velocity is defined as the velocity below which particles begin to deposit to form a moving bed of particles on the bottom of a straight horizontal pipe during slurry-transport operations. The deposition velocity depends on the system geometry and the physical properties of the particles and fluid. An experimental program was implemented to test the stability-map concepts presented in WTP-RPT-175 Rev. 01. Two types of simulant were tested. The first type of simulant was similar to the glass-bead simulants discussed in WTP-RPT-175 Rev. 0 ; it consists of glass beads with a nominal particle size of 150 µm in a kaolin/water slurry. The initial simulant was prepared at a target yield stress of approximately 30 Pa. The yield stress was then reduced, stepwise, via dilution or rheological modifiers, ultimately to a level of <1 Pa. At each yield-stress step, deposition-velocity testing was performed. Testing over this range of yield-stress bounds the expected rheological operating window of the WTP and allows the results to be compared to stability-map predictions for this system. The second simulant was a precipitated hydroxide that simulates HLW pretreated sludge from Hanford waste tank AZ-101. Testing was performed in a manner similar to that for the first simulant over a wide range of yield stresses; however, an additional test of net-positive suction-head required (NPSHR) was performed at each yield stress condition. Unlike the previous simulant, the sizes and densities of the particles that can deposit in the piping are a result of the simulant precipitation process; there is expected to be a complex mixture of particles of various sizes and densities that make it difficult to predict a stability map. The objective of the testing is to observe whether behavior consistent with the stability-map concept occurs in complex simulants with mixtures of different sizes and densities

Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study

PurposeBevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC).Patients and methodsEligible OC patients had measurable (RECIST1.1) or detectable disease, 1-3 prior regimens, performance status (PS) 0-2, and no prior m-TOR inhibitor. All patients received BV 10 mg/kg IV every 2wks. Patients were randomized (1:1) to oral EV (10 mg daily) or placebo stratified by platinum-free interval (PFI), measurable disease and prior BV. Primary endpoint was progression-free survival (PFS); secondary endpoints included safety and response.Results150 patients were randomized to BV with (n = 75) and without (n = 75) EV. Arms were well-balanced for age (median 63: range 28-92), PS (0: 73%, 1-2: 27%), prior regimens (1: 37%, 2: 47%, 3: 16%), prior BV (11%), PFI (&lt;6mos: 65%) and measurable disease (81%). The BV + EV vs BV median PFS was 5.9 vs 4.5 months (hazard ratio [HR] 0.95 (95% CI, 0.66-1.37, p = 0.39)). Median OS was 16.6 vs 17.3 months (HR 1.16 (95% CI, 0.72-1.87, p = 0.55). Objective measurable responses were higher with BV + EV (22% vs 12%). Study removal due to toxicity was higher with BV + EV (29% vs 12%). Toxicity (≥grade 3) from BV + EV were "other GI (mucositis)" (23 vs 1%) and "metabolic/nutrition" (19 vs. 7%); common ≥ grade 2 toxicities with BV + EV were cytopenia, nausea, fatigue and rash.ConclusionThe combination regimen (BV + EV) did not significantly reduce the hazard of progression or death relative to BV and was associated with higher rates of adverse events and study discontinuation when compared to BV alone

BioTIME:a database of biodiversity time series for the Anthropocene

Abstract Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community‐led open‐source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km² (158 cm²) to 100 km² (1,000,000,000,000 cm²). Time period and grain: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. Software format: .csv and .SQL

Are rare species useful species? Obstacles to the conservation of tree diversity in the dry forest zone agro-ecosystems of Mesoamerica

Aim To test the potential to conserve rare dry forest tree and shrub species circa situm.Location Oaxaca, Mexico and Southern Honduras.Methods Local uses (timber, posts and firewood) of species were determined principally through semistructured interviews with 20 rural householders in each of four communities in Honduras and four in Oaxaca. Tree and shrub diversity inventories were carried out in a total of 227 forest patches and parcels of farmland in those eight communities. Species’ conservation priorities were determined using the star system of Hawthorne (1996) and IUCN listings.Results Despite a large number of useful species, remarkably few were also conservation priorities. Useful species were found to be substitutable as is illustrated by Bombacopsis quinata, Cordia alliodora, Guaiacum sanctum and G. coulteri.Conclusions In these areas, circa situm conservation is inhibited by the lack of species that are both rare and useful. Usefulness must be interpreted as a function of substitutability. Natural regeneration provides an abundance of diversity, farmers are unlikely to invest in the management of a species when suitable substitutes are freely available. The key to conserving rare species may be in maintaining or enhancing the value of the landscape elements in which they are found