Rational Clinical Experiment: Assessing Prior Probability and Its Impact on the Success of Phase II Clinical Trials

PubMed Central

Halperin, Daniel M.; Lee, J. Jack; Dagohoy, Cecile Gonzales; Yao, James C.

2015-01-01

Purpose Despite a robust clinical trial enterprise and encouraging phase II results, the vast minority of oncologic drugs in development receive regulatory approval. In addition, clinicians occasionally make therapeutic decisions based on phase II data. Therefore, clinicians, investigators, and regulatory agencies require improved understanding of the implications of positive phase II studies. We hypothesized that prior probability of eventual drug approval was significantly different across GI cancers, with substantial ramifications for the predictive value of phase II studies. Methods We conducted a systematic search of phase II studies conducted between 1999 and 2004 and compared studies against US Food and Drug Administration and National Cancer Institute databases of approved indications for drugs tested in those studies. Results In all, 317 phase II trials were identified and followed for a median of 12.5 years. Following completion of phase III studies, eventual new drug application approval rates varied from 0% (zero of 45) in pancreatic adenocarcinoma to 34.8% (24 of 69) for colon adenocarcinoma. The proportion of drugs eventually approved was correlated with the disease under study (P < .001). The median type I error for all published trials was 0.05, and the median type II error was 0.1, with minimal variation. By using the observed median type I error for each disease, phase II studies have positive predictive values ranging from less than 1% to 90%, depending on primary site of the cancer. Conclusion Phase II trials in different GI malignancies have distinct prior probabilities of drug approval, yielding quantitatively and qualitatively different predictive values with similar statistical designs. Incorporation of prior probability into trial design may allow for more effective design and interpretation of phase II studies. PMID:26261263

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

PubMed

Greenberg, Chelsea B; Boria, Pedro A; Borgatti-Jeffreys, Antonella; Raskin, Rose E; Lucroy, Michael D

2007-01-01

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

Design, analysis, and test verification of advanced encapsulation systems

NASA Technical Reports Server (NTRS)

Mardesich, N.; Minning, C.

1982-01-01

Design sensitivities are established for the development of photovoltaic module criteria and the definition of needed research tasks. The program consists of three phases. In Phase I, analytical models were developed to perform optical, thermal, electrical, and structural analyses on candidate encapsulation systems. From these analyses several candidate systems will be selected for qualification testing during Phase II. Additionally, during Phase II, test specimens of various types will be constructed and tested to determine the validity of the analysis methodology developed in Phase I. In Phse III, a finalized optimum design based on knowledge gained in Phase I and II will be developed. All verification testing was completed during this period. Preliminary results and observations are discussed. Descriptions of the thermal, thermal structural, and structural deflection test setups are included.

International Space Station (ISS)

NASA Image and Video Library

1995-04-17

This computer generated scene of the International Space Station (ISS) represents the first addition of hardware following the completion of Phase II. The 8-A Phase shows the addition of the S-9 truss.

21 CFR 312.47 - Meetings.

Code of Federal Regulations, 2013 CFR

2013-04-01

... meetings held near completion of Phase 3 and before submission of a marketing application (“pre-NDA... uses under investigation. (ii) Eligibility for meeting. While the end-of-Phase 2 meeting is designed... Phase 3 tests are made. The scheduling of an end-of-Phase 2 meeting is not, however, intended to delay...

Barriers to participation in a phase II cardiac rehabilitation programme.

PubMed

Mak, Y M W; Chan, W K; Yue, C S S

2005-12-01

To identify barriers to participation in a phase II cardiac rehabilitation programme and measures that may enhance participation. Prospective study. Regional hospital, Hong Kong. Cardiac patients recruited for a phase I cardiac rehabilitation programme from July 2002 to January 2003. Reasons for not participating in a phase II cardiac rehabilitation programme. Of the 193 patients recruited for a phase I cardiac rehabilitation programme, 152 (79%) patients, with a mean age of 70.3 years (standard deviation, 11.9 years), did not proceed to phase II programme. Eleven (7%) deaths occurred before commencement of phase II and 74 (49%) patients were considered physically unfit. Reasons for the latter included fractures, pain, or degenerative changes in the lower limbs (24%), and co-morbidities such as cerebrovascular accident (19%), chronic renal failure (11%), congestive heart failure (9%), and unstable angina (8%). Phase II rehabilitation was postponed until after completion of scheduled cardiac interventions in 13% of patients. Failure of physicians to arrange the pre-phase II exercise stress test as per protocol was reported in 7% of patients. Other reasons were reported: work or time conflicts (16%), non-compliance with cardiac treatment (5%), financial constraints (4%), self-exercise (3%), fear after exercise stress testing (3%), and patients returning to their original cardiologists for treatment (3%). A significant (79%) proportion of patients did not proceed to a phase II cardiac rehabilitation programme for a variety of reasons. These included physical unfitness, work or time conflicts, and need to attend scheduled cardiac interventions. Further studies are required to determine how to overcome obstacles to cardiac rehabilitation.

Outcome assessment of patients undergoing maxillofacial procedures for the treatment of sleep apnea: comparison of subjective and objective results.

PubMed

Dattilo, David J; Drooger, Scott A

2004-02-01

The purpose of this study was to compare the subjective findings of the Epworth Sleepiness Scale (ESS) to the objective findings of the overnight sleep study (OSS) in 57 patients who underwent phase I and phase II surgery for the correction of obstructive sleep apnea (OSA). Forty-two patients in phase I category (hyoid suspension, palatal surgery, and/or genioglossus advancement) and 15 patients in phase II category (maxillomandibular advancement) were examined. All patients had an OSS and completion of an ESS preoperatively and at a minimum of 8 weeks postoperatively. The results of each test were evaluated to examine any relationship between the improvements of the findings of the OSS to the changes in the ESS. Using accepted criteria, phase I surgery produced an 80% success rate and phase II surgery produced a greater than 95% success rate in both the respiratory disturbance index and the ESS. 1) Both phase I and phase II procedures are effective in treating OSA. 2) Phase II appears to be more effective in treating OSA using both objective and subjective evaluations. 3) Improvement in ESS scores and excessive daytime sleepiness seems to parallel the improvement in OSS scores in patients undergoing surgical correction of OSA.

Mechanochemical induced structural changes in sucrose using the rotational diamond anvil cell

NASA Astrophysics Data System (ADS)

Ciezak-Jenkins, Jennifer A.; Jenkins, Timothy A.

2018-02-01

The response of sucrose to high-pressure and shear conditions has been studied in a rotational diamond anvil cell. Previous experiments conducted by Bridgman and Teller showed divergent behavior in regard to the existence of a rheological explosion under mechanochemical stimuli. Raman spectroscopy confirmed the existence of the isostructural Phase I to Phase II transition near 5 GPa. When subjected to high-pressure and shear, Raman spectra of Phase I showed evidence that while the sucrose molecule underwent significant molecular deformation, there was no evidence of a complete chemical reaction. In contrast, Phase II showed a near-total loss of the in-situ Raman signal in response to shear, suggesting the onset of amorphization or decomposition. The divergent behaviors of Phase I and Phase II are examined in light of the differences in the hydrogen bonding and plasticity of the material.

Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.

PubMed

Van Bambeke, Françoise

2014-11-01

Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

PubMed

Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu

2018-05-01

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.

Project NOAH: Regulating modern sea-level rise. Phase II: Jerusalem Underground

NASA Astrophysics Data System (ADS)

Newman, Walter S.; Fairbridge, Rhodes W.

This proposal builds a high-speed inter-urban express between Jerusalem and Tel Aviv, generates 1500 megawatts of hydroelectric energy, curtails littoral erosion, builds a port along the Israeli Mediterranean coast and demands peaceful cooperation on both sides of the Jordan River. Phase II represents a pilot project demonstrating the feasibility of continuing to regulate world sea-level by a new series of water regulation schemes. Phase I previously described all those projects already completed or underway which have inadvertently and/or unintentionally served the purpose of sea-level regulation. These forms of Phase I sea-level regulation include large and small reservoirs, irrigation projects, water infiltration schemes, farm ponds, and swimming and reflecting pools. All these water storage projects have already exercised a very appreciable brake on 20th century sea-level rise. Phase II outlines a high-visibility proposal which will serve to illustrate the viability of “Project NOAH”.

First results from GERDA Phase II

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-09-01

Gerda is designed for a background-free search of 76Ge neutrinoless double-β decay, using bare Ge detectors in liquid Ar. The experiment was upgraded after the successful completion of Phase I to double the target mass and further reduce the background. Newly-designed Ge detectors were installed along with LAr scintillation sensors. Phase II of data-taking started in Dec 2015 with approximately 36 kg of Ge detectors and is currently ongoing. The first results based on 10.8 kg· yr of exposure are presented. The background goal of 10-3 cts/(keV· kg· yr) is achieved and a search for neutrinoless double-β decay is performed by combining Phase I and II data. No signal is found and a new limit is set at T1/20ν > 5.3 \\cdot {1025} yr (90% C.L.).

A Phase II Trial of Neoadjuvant Preoperative Chemoradiotherapy With S-1 Plus Irinotecan and Radiation in Patients With Locally Advanced Rectal Cancer: Clinical Feasibility and Response Rate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Takeo; Ozawa, Heita; Hatate, Kazuhiko

Purpose: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. Methods and Materials: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m{sup 2} on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80mg/m{sup 2}) was infused on Days 1, 8, 22, and 29. Four or more weeksmore » after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. Results: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. Conclusions: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.« less

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

NASA Technical Reports Server (NTRS)

Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

2007-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

Investigation of contributing factors regarding wrong-way driving on freeways, phase II.

DOT National Transportation Integrated Search

2015-09-01

In the second phase of this project, two major tasks were completed: (1) organizing a national wrong-way driving : (WWD) summit and (2) developing guidelines for reducing WWD on freeways. The first national WWD summit was : held in Edwardsville, Illi...

Phase 2 of Comparative NIR Detector Characterization for NGST

NASA Technical Reports Server (NTRS)

Figer, Donald

2005-01-01

In accordance with NASA Grant and Cooperative Agreement Handbook, 1260.75 (c) (3), enclosed please find a citation of publications resulting from research for the above referenced grant entitled, "Phase II of Comparative NIR Detector Characterization for NGST." This list can also be accessed at http://idtl.stsci.edu/publications.htm. This project was completed with the failure of two Rockwell NIR detectors. The originally proposed measurements could not be completed.

DE-FOA-EE0005502 Advanced Percussive Drilling Technology for Geothermal Exploration and Development Phase II Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Jiann-Cherng; Raymond, David W.; Prasad, Somuri V.

Percussive hammers are a promising advance in drilling technology for geothermal since they rely upon rock reduction mechanisms that are well-suited for use in the hard, brittle rock characteristic of geothermal formations. The project research approach and work plan includes a critical path to development of a high-temperature (HT) percussive hammer using a two- phase approach. The work completed in Phase I of the project demonstrated the viability of percussive hammers and that solutions to technical challenges in design, material technology, and performance are likely to be resolved. Work completed in Phase II focused on testing the findings from Phasemore » I and evaluating performance of the materials and designs at high- operating temperatures. A high-operating temperature (HOT) drilling facility was designed, built, and used to test the performance of the DTH under extreme conditions. Results from the testing indicate that a high-temperature capable hammer can be developed and is a viable alternative for user in the driller's toolbox.« less

Validation of Technical Recommendations. Final Report. ISSOE Managing Student Progress.

ERIC Educational Resources Information Center

Ridley, Dennis; And Others

This report is organized to provide a complete, logical presentation of the major steps taken in the third phase of research on dynamics of dissemination of the Instructional Support System for Occupational Education (ISSOE). It reports on the confirmation and validation of the Phase II Final Report on Dissemination Issues and the Phase III…

Free-Piston Stirling Power Conversion Unit for Fission Power System, Phase II Final Report

NASA Technical Reports Server (NTRS)

Wood, J. Gary; Stanley, John

2016-01-01

In Phase II, the manufacture and testing of two 6-kW(sub e)Stirling engines was completed. The engines were delivered in an opposed 12-kW(sub e) arrangement with a common expansion space heater head. As described in the Phase I report, the engines were designed to be sealed both hermetically and with a bolted O-ring seal. The completed Phase II convertor is in the bolted configuration to allow future disassembly. By the end of Phase II, the convertor had passed all of the final testing requirements in preparation for delivery to the NASA Glenn Research Center. The electronic controller also was fabricated and tested during Phase II. The controller sets both piston amplitudes and maintains the phasing between them. It also sets the operating frequency of the machine. Details of the controller are described in the Phase I final report. Fabrication of the direct-current to direct-current (DC-DC) output stage, which would have stepped down the main controller output voltage from 700 to 120 V(sub DC), was omitted from this phase of the project for budgetary reasons. However, the main controller was successfully built, tested with the engines, and delivered. We experienced very few development issues with this high-power controller. The project extended significantly longer than originally planned because of yearly funding delays. The team also experienced several hardware difficulties along the development path. Most of these were related to the different thermal expansions of adjacent parts constructed of different materials. This issue was made worse by the large size of the machine. Thermal expansion problems also caused difficulties in the brazing of the opposed stainless steel sodium-potassium (NaK) heater head. Despite repeated attempts Sunpower was not able to successfully braze the opposed head under this project. Near the end of the project, Glenn fabricated an opposed Inconel NaK head, which was installed prior to delivery for testing at Glenn. Engine development prior to this was performed using both single- and dual-opposed (common expansion space) Inconel heads with clamp-on electric heaters.

Phase II study of 4'-(9-acridinylamino) methanesulfon-m- anisidide (AMSA) in metastatic melanoma.

PubMed

Legha, S S; Hall, S W; Powell, K C; Burgess, M A; Benjamin, R S; Gutterman, J U; Bodey, G P

1980-01-01

A phase II study of AMSA in previously treated patients with metastatic malignant melanoma was conducted. The dose schedule of AMSA was 40 mg/m2/day for 3 days repeated at 3-week intervals. Among the 30 evaluable patients, one achieved a complete response, one a partial response, and four had minor responses. Side effects included mild nausea and vomiting and moderate degree of myelosuppression. AMSA has poor activity against previously treated metastatic melanoma.

Dynamics of tobacco DNA topoisomerases II in cell cycle regulation: to manage topological constrains during replication, transcription and mitotic chromosome condensation and segregation.

PubMed

Singh, Badri Nath; Achary, V Mohan Murali; Panditi, Varakumar; Sopory, Sudhir K; Reddy, Malireddy K

2017-08-01

The topoisomerase II expression varies as a function of cell proliferation. Maximal topoisomerase II expression was tightly coupled to S phase and G2/M phase via both transcriptional and post-transcriptional regulation. Investigation in meiosis using pollen mother cells also revealed that it is not the major component of meiotic chromosomes, it seems to diffuse out once meiotic chromosomal condensation is completed. Synchronized tobacco BY-2 cell cultures were used to study the role of topoisomerase II in various stages of the cell cycle. Topoisomerase II transcript accumulation was observed during the S- and G2/M- phase of cell cycle. This biphasic expression pattern indicates the active requirement of topoisomerase II during these stages of the cell cycle. Through immuno-localization of topoisomerase II was observed diffusely throughout the nucleoplasm in interphase nuclei, whereas, the nucleolus region exhibited a more prominent immuno-positive staining that correlated with rRNA transcription, as shown by propidium iodide staining and BrUTP incorporation. The immuno-staining analysis also showed that topoisomerase II is the major component of mitotic chromosomes and remain attached to the chromosomes during cell division. The inhibition of topoisomerase II activity using specific inhibitors revealed quite dramatic effect on condensation of chromatin and chromosome individualization from prophase to metaphase transition. Partially condensed chromosomes were not arranged on metaphase plate and chromosomal perturbations were observed when advance to anaphase, suggesting the importance of topoisomerase II activity for proper chromosome condensation and segregation during mitosis. Contrary, topoisomerase II is not the major component of meiotic chromosomes, even though mitosis and meiosis share many processes, including the DNA replication, chromosome condensation and precisely regulated partitioning of chromosomes into daughter cells. Even if topoisomerase II is required for individualization and condensation of meiotic chromosomes, it seems to diffuse out once meiotic chromosomal condensation is completed.

Impact of Satellite Aeronautical Channel on Modem Specifications : Phase II. Oceanic Multipath Measurements and Modem Concepts

DOT National Transportation Integrated Search

1975-01-01

The report completes the analysis initiated in the Phase I report of the effects of oceanic multipath on ranging and data modems for satellite air traffic control systems. The interaction between multipath antenna and apparent measured multipath is d...

Impact of Satellite Aeronautical Channel on Modem Specifications : Phase II. Oceanic Multipath Measurements and Modem Concepts

DOT National Transportation Integrated Search

1975-01-01

This report completes the analysis inititaed in the Phase I report of the effects of oceanic multipath on ranging and data modems for satellite air traffic control systems. The interaction between multipath antenna and apparent measured multipath is ...

Commissioning and Early Operation for the NSLS-II Booster RF System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marques, C.; Cupolo, J.; Davila, P.

2015-05-03

The National Synchrotron Light Source II (NSLS-II) at Brookhaven National Laboratory (BNL) is a third generation 3GeV, 500mA synchrotron light source. We discuss the booster synchrotron RF system responsible for providing power to accelerate an electron beam from 200MeV to 3GeV. The RF system design and construction are complete and is currently in the operational phase of the NSLS-II project. Preliminary operational data is also discussed.

Improvement of General Electric’s Chilled Ammonia Process with the use of Membrane Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muraskin, Dave; Dube, Sanjay; Baburao, Barath

General Electric Environmental Control Solutions (formerly Alstom Power Environmental Control Systems) set out to complete the Phase 1 award requirements for a Phase II renewal application for their project selected under DOE-FOA-0001190 “Small and Large Scale Pilots for Reducing the Cost of CO 2 Capture and Compression”. The project focus was to implement several improvement concepts utilizing membrane technology at the recipient’s Chilled Ammonia Process (CAP) CO 2 capture large-scale pilot plant. The goal was to lower the overall cost of technology. During the development of costs for the preliminary techno-economic assessment (TEA), it became clear that the capital andmore » operating costs of this concept were not economically attractive. All work related to a Phase II renewal application at that point was halted as GE made the decision not to submit a Phase II renewal application. Discussions with DOE resulted in a path towards useful information produced from the design and cost work already completed on the project. With the reverse osmosis (RO) unit providing most of the cost issues, GE would provide a sensitivity analysis of the RO unit with respect to project cost. This information would be included with the Techno-Economic Analysis along with the Technology Gap Analysis.« less

WINCHESTER LAKE, LEWIS COUNTY, IDAHO - CLEAN LAKES PHASE II IMPLEMENTATION AND RESTORATION PROJECT, 1996

EPA Science Inventory

Winchester Lake, Idaho (17060306) is an 85 acre recreation site located approximately 30 miles southeast of Lewiston. The lake has been involved in the U.S. EPA Clean Lakes Program since 1988. The Phase I Diagnostic and Feasibility Study, completed in February 1990, identified t...

Orbital express capture system: concept to reality

NASA Astrophysics Data System (ADS)

Stamm, Shane; Motaghedi, Pejmun

2004-08-01

The development of autonomous servicing of on-orbit spacecraft has been a sought after objective for many years. A critical component of on-orbit servicing involves the ability to successfully capture, institute mate, and perform electrical and fluid transfers autonomously. As part of a Small Business Innovation Research (SBIR) grant, Starsys Research Corporation (SRC) began developing such a system. Phase I of the grant started in 1999, with initial work focusing on simultaneously defining the parameters associated with successful docking while designing to those parameters. Despite the challenge of working without specific requirements, SRC completed development of a prototype design in 2000. Throughout the following year, testing was conducted on the prototype to characterize its performance. Having successfully completed work on the prototype, SRC began a Phase II SBIR effort in mid-2001. The focus of the second phase was a commercialization effort designed to augment the prototype model into a more flight-like design. The technical requirements, however, still needed clear definition for the design to progress. The advent of the Orbital Express (OE) program provided much of that definition. While still in the proposal stages of the OE program, SRC began tailoring prototype redesign efforts to the OE program requirements. A primary challenge involved striking a balance between addressing the technical requirements of OE while designing within the scope of the SBIR. Upon award of the OE contract, the Phase II SBIR design has been fully developed. This new design, designated the Mechanical Docking System (MDS), successfully incorporated many of the requirements of the OE program. SRC is now completing dynamic testing on the MDS hardware, with a parallel effort of developing a flight design for OE. As testing on the MDS progresses, the design path that was once common to both SBIR effort and the OE program begins to diverge. The MDS will complete the scope of the Phase II SBIR work, while the new mechanism, the Orbital Express Capture System, will emerge as a flight-qualified design for the Orbital Express program.

Dietary intakes associated with successful weight loss and maintenance during the Weight Loss Maintenance Trial

PubMed Central

Champagne, Catherine M.; Broyles, Stephanie T; Moran, Laura D.; Cash, Katherine C.; Levy, Erma J.; Lin, Pao-Hwa; Batch, Bryan C.; Lien, Lillian F.; Funk, Kristine L.; Dalcin, Arlene; Loria, Catherine; Myers, Valerie H.

2011-01-01

Background Dietary components effective in weight maintenance efforts have not been adequately identified. Objective To determine impact of changes in dietary consumption on weight loss and maintenance during the Weight Loss Maintenance (WLM) clinical trial. Design WLM was a randomized controlled trial. Successful weight loss participants who completed Phase I of the trial and lost 4kg were randomized to one of three maintenance intervention arms in Phase II and followed for an additional 30 months. Participants/setting The multicenter trial was conducted from 2003–2007. This substudy included 828 successful weight loss participants. Methods Dietary Measures The Block Food Frequency Questionnaire (FFQ) was used to assess nutrient intake levels and food group servings. Carbohydrates, proteins, fats, dietary fiber and fruit/vegetable and dairy servings were utilized as predictor variables. Data collection The FFQ was collected on all participants at study entry (beginning of Phase I). Those randomized to Phase II completed the FFQ at three additional time points; randomization (beginning of Phase II), 12 and 30 months. Intervention The main intervention focused on long term maintenance of weight loss using the Dietary Approaches to Hypertension (DASH) diet. This substudy examined whether changes to specific dietary variables were associated with weight loss and maintenance. Statistical analyses performed Linear regression models that adjusted for change in total energy examined the relationship between changes in dietary intake and weight for each time period. Site, age, race, sex, and a race-sex interaction were included as covariates. Results Participants who substituted protein for fat lost, on average, 0.33 kg per 6-months during Phase I (p<0.0001) and 0.07 kg per 6-months during Phase II (p<0.0001) per 1% increase in protein. Increased intake of fruits and vegetables was associated with weight loss in Phases I and II: 0.29 kg per 6-months (p<0.0001) and 0.04 kg per 6-months (p=0.0062), respectively, per 1-serving increase. Substitution of carbohydrates for fat and protein for carbohydrates were associated with weight loss during both phases. Increasing dairy intake was associated with significant weight loss during Phase II (−0.17 kg per 6-months per 1-serving increase, p=0.0002), but not in Phase I. Dietary fiber revealed no significant findings. Conclusion Increasing fruits, vegetables, and low-fat dairy may help achieve weight loss and maintenance. PMID:22117658

Innovative grinding wheel design for cost-effective machining of advanced ceramics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Licht, R.H.; Kuo, P.; Liu, S.

2000-05-01

This Final Report covers the Phase II Innovative Grinding Wheel (IGW) program in which Norton Company successfully developed a novel grinding wheel for cost-effective cylindrical grinding of advanced ceramics. In 1995, Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics using small prototype wheels. The Phase II program was initiated to scale-up the new superabrasive wheel specification to larger diameters, 305-mm to 406-mm, required for most production grinding of cylindrical ceramic parts, and to perform in-house and independent validation grinding tests.

Status of the Advanced Mirror Technology Development (AMTD) Phase 2, 1.5m ULE(Registered Trademark) Mirror

NASA Technical Reports Server (NTRS)

Egerman, Robert; Matthews, Gary W.; Johnson, Matthew; Ferland, Albert; Stahl, H. Philip; Eng, Ron; Effinger, Michael R.

2015-01-01

The Decadal Survey stated that an advanced large-aperture ultraviolet, optical, near-infrared (UVOIR) telescope is required to enable the next generation of compelling astrophysics and exoplanet science; and, that present technology is not mature enough to affordably build and launch any potential UVOIR mission concept. Under Science and Technology funding, NASA's Marshall Space Flight Center (MSFC) and Exelis have developed a more cost effective process to make up to 4m monolithic spaceflight UV quality, low areal density, thermally and dynamically stable primary mirrors. Under a Phase I program, a proof of concept mirror was completed at Exelis and tested down to 250K at MSFC which would allow imaging out to 2.5 microns. In 2014, Exelis and NASA started a Phase II program to design and build a 1.5m mirror to demonstrate lateral scalability to a 4m monolithic primary mirror. The current status of the Phase II development program will be provided along with a Phase II program summary.

Exploring pharmacy and home-based sexually transmissible infection testing

PubMed Central

Habel, Melissa A.; Scheinmann, Roberta; Verdesoto, Elizabeth; Gaydos, Charlotte; Bertisch, Maggie; Chiasson, Mary Ann

2015-01-01

Background This study assessed the feasibility and acceptability of pharmacy and home-based sexually transmissible infection (STI) screening as alternate testing venues among emergency contraception (EC) users. Methods The study included two phases in February 2011–July 2012. In Phase I, customers purchasing EC from eight pharmacies in Manhattan received vouchers for free STI testing at onsite medical clinics. In Phase II, three Facebook ads targeted EC users to connect them with free home-based STI test kits ordered online. Participants completed a self-administered survey. Results Only 38 participants enrolled in Phase I: 90% female, ≤29 years (74%), 45% White non-Hispanic and 75% college graduates; 71% were not tested for STIs in the past year and 68% reported a new partner in the past 3 months. None tested positive for STIs. In Phase II, ads led to >45 000 click-throughs, 382 completed the survey and 290 requested kits; 28% were returned. Phase II participants were younger and less educated than Phase I participants; six tested positive for STIs. Challenges included recruitment, pharmacy staff participation, advertising with discretion and cost. Conclusions This study found low uptake of pharmacy and home-based testing among EC users; however, STI testing in these settings is feasible and the acceptability findings indicate an appeal among younger women for testing in non-traditional settings. Collaborating with and training pharmacy and medical staff are key elements of service provision. Future research should explore how different permutations of expanding screening in non-traditional settings could improve testing uptake and detect additional STI cases. PMID:26409484

Exploring pharmacy and home-based sexually transmissible infection testing.

PubMed

Habel, Melissa A; Scheinmann, Roberta; Verdesoto, Elizabeth; Gaydos, Charlotte; Bertisch, Maggie; Chiasson, Mary Ann

2015-11-01

Background This study assessed the feasibility and acceptability of pharmacy and home-based sexually transmissible infection (STI) screening as alternate testing venues among emergency contraception (EC) users. The study included two phases in February 2011-July 2012. In Phase I, customers purchasing EC from eight pharmacies in Manhattan received vouchers for free STI testing at onsite medical clinics. In Phase II, three Facebook ads targeted EC users to connect them with free home-based STI test kits ordered online. Participants completed a self-administered survey. Only 38 participants enrolled in Phase I: 90% female, ≤29 years (74%), 45% White non-Hispanic and 75% college graduates; 71% were not tested for STIs in the past year and 68% reported a new partner in the past 3 months. None tested positive for STIs. In Phase II, ads led to >45000 click-throughs, 382 completed the survey and 290 requested kits; 28% were returned. Phase II participants were younger and less educated than Phase I participants; six tested positive for STIs. Challenges included recruitment, pharmacy staff participation, advertising with discretion and cost. This study found low uptake of pharmacy and home-based testing among EC users; however, STI testing in these settings is feasible and the acceptability findings indicate an appeal among younger women for testing in non-traditional settings. Collaborating with and training pharmacy and medical staff are key elements of service provision. Future research should explore how different permutations of expanding screening in non-traditional settings could improve testing uptake and detect additional STI cases.

Portable microfluidic platform for real-time, high sensitive detection and identification of trichloroethylene and other organochloride compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Erik

In this successful SBIR Phase II effort, HJ Science & Technology, Inc. has designed and built a novel portable instrument capable of performing automated aqueous organochloride (chlorinated solvent) speciation analysis for environmental monitoring at DoE sites. Our technique employs performing organochloride conjugation, labeling the conjugate with an efficient fluorophore, and performing on-chip capillary electrophoresis separation with laser induced fluorescence detection. The key component of the portable instrument is a novel microfluidic chip capable of complete “end-to-end” automation of sample preparation, conjugation, labeling, and μCE separation and detection. In addition, the Phase II prototype includes key supporting instrumentation such as themore » optical module, pneumatic manifold, electronics, software, etc. As such, we have achieved all of the following 4 Phase II technical objectives: 1) Further refine and optimize the “on-chip” automation of the organochloride conjugation and labeling protocol, 2) Further improve the microfluidic chip fabrication process and the pneumatic manifold design in order to address issues related to performance consistency, product yield, performance reliability, and user friendliness, 3) Design and build the supporting components of the Phase II prototype including optical module, electronics, and software, and 4) Assemble the Phase II prototype hardware.« less

Using Data Augmentation to Facilitate Conduct of Phase I–II Clinical Trials with Delayed Outcomes

PubMed Central

Jin, Ick Hoon; Liu, Suyu; Thall, Peter F.; Yuan, Ying

2014-01-01

A practical impediment in adaptive clinical trials is that outcomes must be observed soon enough to apply decision rules to choose treatments for new patients. For example, if outcomes take up to six weeks to evaluate and the accrual rate is one patient per week, on average three new patients will be accrued while waiting to evaluate the outcomes of the previous three patients. The question is how to treat the new patients. This logistical problem persists throughout the trial. Various ad hoc practical solutions are used, none entirely satisfactory. We focus on this problem in phase I–II clinical trials that use binary toxicity and efficacy, defined in terms of event times, to choose doses adaptively for successive cohorts. We propose a general approach to this problem that treats late-onset outcomes as missing data, uses data augmentation to impute missing outcomes from posterior predictive distributions computed from partial follow-up times and complete outcome data, and applies the design’s decision rules using the completed data. We illustrate the method with two cancer trials conducted using a phase I–II design based on efficacy-toxicity trade-offs, including a computer stimulation study. PMID:25382884

Advanced Natural Gas Reciprocating Engines(s)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zurlo, James

The ARES program was initiated in 2001 to improve the overall brake thermal efficiency of stationary, natural gas, reciprocating engines. The ARES program is a joint award that is shared by Dresser, Inc., Caterpillar and Cummins. The ARES program was divided into three phases; ARES I (achieve 44% BTE), ARES II (achieve 47% BTE) and ARES III (achieve 50% BTE). Dresser, Inc. completed ARES I in March 2005 which resulted in the commercialization of the APG1000 product line. ARES II activities were completed in September 2010 and the technology developed is currently being integrated into products. ARES III activities beganmore » in October 2010. The ARES program goal is to improve the efficiency of natural gas reciprocating engines. The ARES project is structured in three phases with higher efficiency goals in each phase. The ARES objectives are as follows: 1. Achieve 44% (ARES I), 47% (ARES II), and 50% brake thermal efficiency (BTE) as a final ARES III objective 2. Achieve 0.1 g/bhp-hr NOx emissions (with after-treatment) 3. Reduce the cost of the produced electricity by 10% 4. Improve or maintain reliability, durability and maintenance costs« less

SELDI Validation Study Phase II — EDRN Public Portal

Cancer.gov

This project –A Comprehensive Program for the Validation of Prostate Cancer Early Detection with Novel Protein Identification Techniques -- is divided into three phases. The goal of Phase I was to assess the reproducibility and portability of Surface-Enhanced Laser Desorption and Ionization time-of-flight mass spectrometry (SELDI-TOF-MS) using protein profiles generated from serum. Phase I was recently successfully completed at six institutions using a single source of pooled sera.

Report of the Computer Assisted Instruction Project in the Faculty of Nursing at the University of Calgary.

ERIC Educational Resources Information Center

Hannah, Kathryn

Since August of 1976, the Faculty of Nursing at the University of Calgary has developed and implemented a four-phase computer assisted instruction (CAI) project. In Phase I, the pilot project to demonstrate effectiveness of CAI as an alternative teaching strategy in that setting has been completed and replication is on-going. In Phase II,…

Commercial-Off-the-Shelf (COTS), Volatile Organic Compounds (VOCs) and Hazardous Air Pollutants (HAPs)-Free, Non-Chromate Low Temperature Powder Coating (LTPC) System for United States Air Force use (PHASE II )

DTIC Science & Technology

2017-09-12

and Hazardous Air Pollutants (HAPs)-Free, non -chromate low temperature powder coating (LTPC) system for United States Air Force use PHASE II PR...required to support and successfully complete this effort. 1.1 Objective(s). The Contractor shall be required to demonstrate a non -chromate...5.0 General Information 5.1 Continuation of Mission-Essential Services During a Crisis. The Functional Commander (FC) or civilian equivalent has

38 CFR 21.184 - “Evaluation and planning” status.

Code of Federal Regulations, 2010 CFR

2010-07-01

... prior initial evaluations, or (ii) Current or previous individualized rehabilitation plans. (b... every reasonable effort to enable the veteran to complete the evaluation and planning phase of the...

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

Geographic Mobility of Postsecondary Occupational Education Graduates. Phase II.

ERIC Educational Resources Information Center

Winter, Gene M.; Fadale, LaVerna M.

This report of the second phase of a study of the geographic mobility patterns of postsecondary occupational education graduates in New York State provides a further examination of reasons for the mobility of program completers, verifies the general magnitude of the identified mobility trends, and examines the occupational status of program…

Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma

PubMed Central

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Ishizawa, Kenichi; Uike, Naokuni; Uchida, Toshiki; Suzuki, Tatsuya; Aoki, Tomohiro; Watanabe, Takashi; Maruyama, Dai; Yokoyama, Masahiro; Takubo, Takatoshi; Kagehara, Hideaki; Matsushima, Takafumi

2014-01-01

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma. PMID:24814862

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Midodrine as a Countermeasure for Post-spaceflight Orthostatic Hypotension

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Ziegler, Michael G.; Waters, Wendy W.; Meck, Janice V.

2007-01-01

Up to 30 % of astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release during upright posture following short duration spaceflight. We hypothesize that the (alpha)1-adrenergic agonist midodrine will be an effective countermeasure. This study is being conducted in 2 phases. The first phase is complete and consisted testing six short duration crew members. All of these subjects participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine was administered after landing, 1 hour before testing. Hemodynamic variables were compared between the 2 flights. Midodrine improved stroke volume, cardiac output, systolic pressure and heart rate, without increasing vascular resistance. None of these subjects experienced orthostatic hypotension on landing day. Phase II is similar to phase I, except that midodrine is ingested in flight (near TIG) and the tilt test is performed immediately after landing on the CTV. One crewmember has completed phase II testing. This crewmember had no evidence of orthostatic hypotension or presyncope, four additional crewmembers have volunteered for this study. To date, midodrine has been shown to be a safe and effective countermeasure to post-spaceflight orthostatic hypotension.

Principle Findings from Development of a Recirculated Exhaust Gas Intake Sensor (REGIS) Enabling Cost-Effective Fuel Efficiency Improvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnabel, Claus

Kick-off of the Bosch scope of work for the REGIS project started in October 2012. The primary work-packages included in the Bosch scope of work were the following: overall project management, development of the EGR sensor (design of sensor element, design of protection tube, and design of mounting orientation), development of EGR system control strategy, build-up of prototype sensors, evaluation of system performance with the new sensor and the new control strategy, long-term durability testing, and development of a 2nd generation sensor concept for continued technology development after the REGIS project. The University of Clemson was a partner with Boschmore » in the REGIS project. The Clemson scope of work for the REGIS project started in June 2013. The primary work-packages included in the Clemson scope of work were the following: development of EGR system control strategy, and evaluation of system performance with the new sensor and new control strategy. This project was split into phase I, phase II and phase III. Phase I work was completed by the end of June 2014 and included the following primary work packages: development of sensor technical requirements, assembly of engine testbench at Clemson, design concept for sensor housing, connector, and mounting orientation, build-up of EGR flow test benches at Bosch, and build-up of first sensor prototypes. Phase II work was completed by the end of June 2015 and included the following primary work pack ages: development of an optimizing function and demonstration of robustness of sensor, system control strategy implementation and initial validation, completion of engine in the loop testing of developed control algorithm, completion of sensor testing including characteristic line, synthetic gas test stand, and pressure dependency characterization, demonstration of benefits of control w/o sensing via simulation, development of 2nd generation sensor concept. Notable technical achievements from phase II were the following: publication of two new technical papers by Clemson detailing the control strategies used for the EGR system control. The two papers was published in the 2016 SAE World Congress in April 2016. The titles of each paper are, “Physics-Based Exhaust Pressure and Temperature Estimation for Low Pressure EGR Control in Turbocharged Gasoline Engines,” by K. Siokos, and “A Control Algorithm for Low Pressure – EGR Systems using a Smith Predictor with Intake Oxygen Sensor Feedback”, by R. Koli. All phase III work packages have been completed. The primary work packages in phase III were the following: completion of long-term sensor durability testing, final demonstration of benefits of EGR control w/o sensing, final decision of the second generation sensor development path.« less

Phase II study of the tetrahydropyranyl adriamycin-cyclophosphamide, vincristine, and prednisolone regimen combined with rituximab as first-line treatment for elderly patients with diffuse large B-cell lymphoma.

PubMed

Kasahara, Senji; Hara, Takeshi; Tsurumi, Hisashi; Goto, Naoe; Kitagawa, Jun-Ichi; Kanemura, Nobuhiro; Yoshikawa, Takeshi; Goto, Hideko; Fukuno, Kenji; Yamada, Toshiki; Sawada, Michio; Takahashi, Takeshi; Takami, Tsuyoshi; Moriwaki, Hisataka

2011-04-01

The anthracycline drug pirarubicin (tetrahydropyranyl adriamycin; THP) apparently has fewer cardiotoxic effects than doxorubicin. We previously described the benefit of the THP-COP regimen comprising cyclophosphamide, THP, vincristine, and prednisolone for elderly patients with diffuse large B-cell lymphoma (DLBCL). However, that study was completed before rituximab (R) was introduced into clinical practice. Here we report a phase II study of the THP-COP regimen combined with R (R-THP-COP) every 3 weeks. The complete response and 3-year overall survival rates was 63% and 53%, respectively, and no deaths were related to the regimen. We conclude that the R-THP-COP regimen is safe and effective for patients with DLBCL. Based on these results, a randomized controlled trial of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and R-THP-COP as a phase III study is ongoing.

Labeled carbon dioxide (C18O2): an indicator gas for phase II in expirograms.

PubMed

Schulz, Holger; Schulz, Anne; Eder, Gunter; Heyder, Joachim

2004-11-01

Carbon dioxide labeled with 18O (C18O2) was used as a tracer gas for single-breath measurements in six anesthetized, mechanically ventilated beagle dogs. C18O2 is taken up quasi-instantaneously in the gas-exchanging region of the lungs but much less so in the conducting airways. Its use allows a clear separation of phase II in an expirogram even from diseased individuals and excludes the influence of alveolar concentration differences. Phase II of a C18O2 expirogram mathematically corresponds to the cumulative distribution of bronchial pathways to be traversed completely in the course of exhalation. The derivative of this cumulative distribution with respect to respired volume was submitted to a power moment analysis to characterize volumetric mean (position), standard deviation (broadness), and skewness (asymmetry) of phase II. Position is an estimate of dead space volume, whereas broadness and skewness are measures of the range and asymmetry of functional airway pathway lengths. The effects of changing ventilatory patterns and of changes in airway size (via carbachol-induced bronchoconstriction) were studied. Increasing inspiratory or expiratory flow rates or tidal volume had only minor influence on position and shape of phase II. With the introduction of a postinspiratory breath hold, phase II was continually shifted toward the airway opening (maximum 45% at 16 s) and became steeper by up to 16%, whereas skewness showed a biphasic response with a moderate decrease at short breath holding and a significant increase at longer breath holds. Stepwise bronchoconstriction decreased position up to 45 +/- 2% and broadness of phase II up to 43 +/- 4%, whereas skewness was increased up to twofold at high-carbachol concentrations. Under all circumstances, position of phase II by power moment analysis and dead space volume by the Fowler technique agreed closely in our healthy dogs. Overall, power moment analysis provides a more comprehensive view on phase II of single-breath expirograms than conventional dead space volume determinations and may be useful for respiratory physiology studies as well as for the study of diseased lungs.

Cadmium Alternatives for High-Strength Steel JTP - Phase 2

DTIC Science & Technology

2008-02-27

Project Overview Objective • Assess DoD- selected Cadmium alternatives in accordance with the DoD-approved Joint Test Protocol (JTP) for both...HE and adhesion testing): NAVAIR (complete) – Phase II (JTP test matrix): AFRL/CTC – Phase III (Testing for Threaded Fasteners): ARL • Selection of...Curry • Hill AFB – Mr. Nate Hughes • Alumiplate – Mr. Gus Vallejo • Marshall Labs – Mr. John Marshall U.S. AIR FORCE Phase I Overview and Selection

A putative carbohydrate-binding domain of the lactose-binding Cytisus sessilifolius anti-H(O) lectin has a similar amino acid sequence to that of the L-fucose-binding Ulex europaeus anti-H(O) lectin.

PubMed

Konami, Y; Yamamoto, K; Osawa, T; Irimura, T

1995-04-01

The complete amino acid sequence of a lactose-binding Cytisus sessilifolius anti-H(O) lectin II (CSA-II) was determined using a protein sequencer. After digestion of CSA-II with endoproteinase Lys-C or Asp-N, the resulting peptides were purified by reversed-phase high performance liquid chromatography (HPLC) and then subjected to sequence analysis. Comparison of the complete amino acid sequence of CSA-II with the sequences of other leguminous seed lectins revealed regions of extensive homology. The amino acid sequence of a putative carbohydrate-binding domain of CSA-II was found to be similar to those of several anti-H(O) leguminous lectins, especially to that of the L-fucose-binding Ulex europaeus lectin I (UEA-I).

Novel Surface Modification Method for Ultrasupercritical Coal-Fired Boilers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, T. Danny

2013-05-22

US Department of Energy seeks an innovative coating technology for energy production to reduce the emission of SOx, NOx, and CO2 toxic gaseous species. To realize this need, Inframat Corporation (IMC) proposed an SPS thermal spray coating technique to produce ultrafine/nanocoatings that can be deposited onto the surfaces of high temperature boiler tubes, so that higher temperatures of boiler operation becomes possible, leading to significantly reduced emission of toxic gaseous species. It should be noted that the original PI was Dr. Xinqing Ma, who after 1.5 year conducting this project left Inframat in December, 2008. Thus, the PI was transferredmore » to Dr. Danny Xiao, who originally co-authored the proposal with Dr. Ma, in order to carry the project into a completion. Phase II Objectives: The proposed technology has the following attributes, including: (1). Dispersion of a nanoparticle or alloyed particle in a solvent to form a uniform slurry feedstock; (2). Feeding of the slurry feedstock into a thermal spray flame, followed by deposition of the slurry feedstock onto substrates to form tenacious nanocoatings; (3). High coating performance: including high bonding strength, and high temperature service life in the temperature range of 760oC/1400oF. Following the above premises, our past Phase I project has demonstrated the feasibility in small scale coatings on boiler substrates. The objective of this Phase II project was to focus on scale-up the already demonstrated Phase I work for the fabrication of SPS coatings that can satisfy DOE's emission reduction goals for energy production operations. Specifically, they are: (1). Solving engineering problems to scale-up the SPS-HVOF delivery system to a prototype production sub-delivery system; (2). Produce ultrafine/nanocoatings using the scale-up prototype system; (3). Demonstrate the coated components using the scale-up device having superior properties. Proposed Phase II Tasks: In the original Phase II proposal, we have six (6) technical tasks plus one (1) reporting task, as described below: Task 1 Scale-up and optimize the SPS process; Task 2 Coating design and fabrication with desired microstructure; Task 3 Evaluate microstructure and physical properties; Task 4 Test performance of long-term corrosion and erosion; Task 5 Test mechanical property and reliability; Task 6 Coating of a prototype boiler tube for evaluation; Task 7 Reporting task. To date, we have already completed all the technical tasks of 1 through 6. Major Phase II Achievements: In this four (4) year working period, Inframat had spent great effort to complete the proposed tasks. The project had been completed; the goals have been accomplished. Major achievements obtained include: (1). Developed a prototype scale-up slurry feedstock delivery system for thermal spray coatings; (2). Successfully coated high performance coatings using this scale-up slurry delivery system; (3). Commercial applications in energy efficiency and clean energy components have been developed using this newly fabricated slurry feedstock delivery system.« less

Metabolism of brucine: the important metabolic pathways of dihydroindole-type alkaloid for excretion in rats.

PubMed

Tian, Ji-Xin; Wang, Min; Xu, Lei; Tian, Yuan; Song, Rui; Xu, Feng-Guo; Zhang, Zun-Jian

2014-01-01

Brucine is a widely prescribed glycine antagonist, but a complete understanding of its metabolic pathway is still lacking. The present work represents the first investigation of in vivo metabolism of brucine in rats using LC-ESI-ion trap-TOF-MS. A total of 12 Phase I and five Phase II metabolites were tentatively identified. Brucine can be metabolized by hydrolysis, demethylation and methoxylation, in addition to diverse oxidations in a Phase I manner followed by glucuronidation in Phase II metabolism. Both the renal and biliary routes were observed for the excretion of brucine and its metabolites. Our results update the metabolism and disposition data on brucine, which provides basic information for better understanding of the pharmacological and toxicological activities of brucine-containing medicines.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noel, Donna

This project integrated state-of-the-art exploration technologies with a geologic framework and reservoir modeling to ultimately determine the efficacy of future geothermal production within the PLPT reservation. The information gained during this study should help the PLPT to make informed decisions regarding construction of a geothermal power plant. Additional benefits included the transfer of new technologies and geothermal data to the geothermal industry and it created and/or preserved nearly three dozen jobs accordance with the American Recovery and Reinvestment Act of 2009. A variety of tasks were conducted to achieve the above stated objectives. The following are the tasks completed withinmore » the project: 1. Permitting 2. Shallow temperature survey 3. Seismic data collection and analysis 4. Fracture stress analysis 5. Phase I reporting Permitting 7. Shallow temperature survey 8. Seismic data collection and analysis 9. Fracture stress analysis 10. Phase I reporting 11. Drilling two new wells 12. Borehole geophysics 13. Phase II reporting 14. Well testing and geochemical analysis 15. Three-dimensional geologic model 16. Three-dimensional reservoir analysis 17. Reservation wide geothermal potential analysis 18. Phase III reporting Phase I consisted of tasks 1 – 5, Phase II tasks 6 – 8, and Phase III tasks 9 – 13. This report details the results of Phase III tasks. Reports are available for Phase I, and II as separate documents.« less

Preconcentration of trace lead and iron on activated carbon functionalized by o-Anisic acid derivatives prior to their determination in environmental samples.

PubMed

Tian, Hua; Hu, Zheng; He, Qun; Liu, Xueliang; Zhang, Li; Chang, Xijun

2012-07-01

Two solid-phase adsorbents (phase I and phase II) were synthesized successfully that o-Anisic acid derivatives were evenly functionalized on the surface of activated carbon. It was certified that the two adsorbents were applied to preconcentrate and separate trace levels of Pb(II) and Fe(III) from natural liquid samples with satisfactory results. It can be found that the adsorption capacity of the ions adsorbed on phase I and phase II was 48.3 and 85.7 mg g(-1) for Pb(II), 39.5 and 72.5 mg g(-1) for Fe(III), respectively. The detection limit (3σ) of the method separated on phase I and phase II was 0.12 and 0.09 ng mL(-1) for Pb(II), 0.23 and 0.17 ng mL(-1) for Fe(III), respectively. The relative standard deviation (R.S.D.) of the method was lower than 3.0%. The adsorption and desorption property of two kinds of adsorbents was comparatively studied, respectively. The adsorption selectivity of heavy metal ions at certain pH, the adsorption kinetics, the condition of complete elution, the effect of coexisting ions, the adsorption capacity and adsorption isotherm modes were examined. Based on the experimental datum determined by inductively coupled plasma optical emission spectrometry (ICP-OES), it was certified that the adsorption on the surface of adsorbents was in strict accordance with the monolayer adsorption principle. The structural features of series of multidentate ligand modified on adsorption matrix had been obtained. These conclusions can provide reference for synthesizing an efficient adsorbent which is specific to remove a particular kind of contaminant. Copyright © 2012 Elsevier B.V. All rights reserved.

EXTRA-A Multicenter Phase II Study of Chemoradiation Using a 5 Day per Week Oral Regimen of Capecitabine and Intravenous Mitomycin C in Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glynne-Jones, Rob; Meadows, Helen; UCL Cancer Trials Centre, London

Purpose: 5-Fluorouracil (5-FU) + mitomycin C (MMC)-based chemoradiotherapy is standard treatment for patients with epidermoid anal carcinoma. Clinical trials in other cancers have confirmed 5-FU can successfully be replaced by the oral fluoropyrimidine capecitabine. This phase II trial aimed to determine the feasibility, toxicity, and efficacy of capecitabine, MMC and radiotherapy (RT) in anal cancer patients. Methods and Materials: Radiotherapy comprised the schedule of the UK Anal Cancer Trial (ACT) II trial (50.4 Gy in 28 fractions of 1.8 Gy). With MMC (12 mg/m{sup 2}) on Day 1 and capecitabine on each RT treatment day in two divided doses (825more » mg/m{sup 2} b.i.d). The endpoints were complete response at 4 weeks, local control at 6 months and toxicity. Results: Thirty-one patients entered the trial. The median age was 61 years (range 45-86) with 14 males and 17 females. Compliance with chemotherapy with no dose interruptions or delays was 68%, and with RT was 81%. Eighteen (58%) patients completed both modalities of treatment as planned. Dose-limiting Grade 3 or 4 diarrhea was seen in 1 of 31 patients. Three patients experienced Grade 3 neutropenia. There were no treatment-related deaths. Four weeks following completion of chemoradiation, 24 patients (77%) had a complete clinical response, and 4 (16%) a partial response. With a median follow-up of 14 months, three locoregional relapses occurred. Conclusions: Capecitabine with MMC and RT in with patients anal carcinoma is well tolerated, with minimal toxicity and acceptable compliance. We recommend testing this schedule in future national Phase III studies in anal cancer.« less

High-pressure phase transitions, amorphization, and crystallization behaviors in Bi2Se3.

PubMed

Zhao, Jinggeng; Liu, Haozhe; Ehm, Lars; Dong, Dawei; Chen, Zhiqiang; Gu, Genda

2013-03-27

The phase transition, amorphization, and crystallization behaviors of the topological insulator bismuth selenide (Bi2Se3) were discovered by performing in situ high-pressure angle-dispersive x-ray diffraction experiments during an increasing, decreasing, and recycling pressure process. In the compression process, Bi2Se3 transforms from the original rhombohedral structure (phase I(A)) to a monoclinic structure (phase II) at about 10.4 GPa, and further to a body-centered tetragonal structure (phase III) at about 24.5 GPa. When releasing pressure to ambient conditions after the complete transformation from phase II to III, Bi2Se3 becomes an amorphous solid (AM). In the relaxation process from this amorphous state, Bi2Se3 starts crystallizing into an orthorhombic structure (phase I(B)) about five hours after releasing the pressure to ambient. A review of the pressure-induced phase transition behaviors of A2B3-type materials composed from the V and VI group elements is presented.

Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herchenhorn, Daniel, E-mail: herchenhorn@hotmail.co; Dias, Fernando L.; Viegas, Celia M.P.

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuingmore » during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.« less

Effects of phase II cardiac rehabilitation on job stress and health-related quality of life after return to work in middle-aged patients with acute myocardial infarction.

PubMed

Yonezawa, Ryusuke; Masuda, Takashi; Matsunaga, Atsuhiko; Takahashi, Yumi; Saitoh, Masakazu; Ishii, Akira; Kutsuna, Toshiki; Matsumoto, Takuya; Yamamoto, Kazuya; Aiba, Naoko; Hara, Miyako; Izumi, Tohru

2009-05-01

The aim of the present study was to clarify the effects of phase II cardiac rehabilitation (CR) on job stress and health-related quality of life (HRQOL) after return to work in middle-aged patients with acute myocardial infarction (AMI). A total of 109 middle-aged outpatients (57 +/- 7 years) who completed a phase I CR program after AMI were enrolled, 72 of whom participated in a phase II CR program for 5 months after hospital discharge (CR group) and 37 who discontinued the phase II CR program after the discharge (non-CR group). Job stress was assessed at 6 months after the AMI using a brief job stress questionnaire containing questions related to job stressors, worksite support, level of satisfaction with work or daily life, and psychological distress. HRQOL was assessed using the short-form 36-item health survey (SF-36) at hospital discharge and at 3 and 6 months after the AMI. There were no significant differences in clinical and occupational characteristics between the CR and non-CR groups. The CR group patients exhibited significantly better results for job stressors and psychological distress and higher SF-36 scores at 6 months after the AMI, as compared with those in the non-CR group. These findings suggest that discontinuing a phase II CR program induced chronic psychosocial stress after return to work in these middle-aged post-AMI patients.

Effects of Simulated Surface Effect Ship Motions on Crew Habitability. Phase II. Volume 1. Summary Report and Comments

DTIC Science & Technology

1981-04-01

one 24-hour exposure to that condition may be regarded as the most complete and unbiased for determining some effects of a type of simulated SES...eliminated entirely. The ability to predict in advance the resultant effects of motion exposure thus seems to depend on the existance of a given...F• 198OF1L-0/I- =•RAI. )81 -• i . _j EFFECT OF.SIMULATED 1 S URFACE EFFECT SHIP J•OTIONS_2 ON CREW HABITABILITY 1PHASE 1J_ "I ,,OLUME 1 iI SUMMARY

Evaluating roadway subsurface drainage practices - phase II.

DOT National Transportation Integrated Search

2015-04-01

Well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of : Transportation (DOT). The recently completed Iowa Highway Research Board (IHRB) project TR-643 provided extensive : insights into Iowa...

Discontinuation of orthokeratology on eyeball elongation (DOEE).

PubMed

Cho, P; Cheung, S W

2017-04-01

To evaluate and compare changes in axial elongation, over a 14-month period, in subjects who discontinued and then resumed ortho-k lens wear with those who continued to wear their lenses or spectacles following a 2-year myopia control study. This single masked, prospective study recruited subjects who had just completed a 2-year myopia control study. Ortho-k subjects were classified as Group OKc, in which subjects continued ortho-k lens wear for the duration of the study; or Group OKd in which subjects discontinued lens wear for seven months and wore single-vision spectacles (Phase I) and then resumed ortho-k lens wear for another seven months (Phase II). Spectacle-wearing control subjects from the initial myopia control study continued wearing spectacles as control subjects. Axial lengths were measured at scheduled visits using the IOLMaster. Thirteen, 16, and 15 Control, OKc, and OKd subjects, aged 8-14 years, respectively completed the study. Significant increase in axial elongation was found in OKd subjects only in Phase I but not in Phase II. On resuming lens wear, in Phase II, the rate of axial elongation was no longer significantly different from those of the Control or OKc subjects. Stopping ortho-k lens wear at or before the age of 14 years led to a more rapid increase in axial length; comparable to those wearing spectacles during the initial 2-year myopia control study, but greater than the Control and OKc group in this study. Axial elongation slowed again with resumed lens wear after six months. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Development of an X-Band 50 MW Multiple Beam Klystron

NASA Astrophysics Data System (ADS)

Song, Liqun; Ferguson, Patrick; Ives, R. Lawrence; Miram, George; Marsden, David; Mizuhara, Max

2003-12-01

Calabazas Creek Research, Inc. is developing an X-band 50 MW multiple beam klystron (MBK) on a DOE SBIR Phase II grant. The electrical design and preliminary mechanical design were completed on the Phase I. This MBK consists of eight discrete klystron circuits driven by eight electron beams located symmetrically on a circle with a radius of 6.3 cm. Each beam operates at 190 kV and 66 A. The eight beam electron gun is in development on a DOE SBIR Phase II grant. Each circuit consists of an input cavity, two gain cavities, three penultimate cavities, and a three cavity output circuit operating in the PI/2 mode. Ring resonators were initially proposed for the complete circuit; however, low beam — wave interaction resulted in the necessity to use discrete cavities for all eight circuits. The input cavities are coupled via hybrid waveguides to ensure constant drive power amplitude and phase. The output circuits can either be combined using compact waveguide twists driving a TE01 high power window or combined into a TM04 mode converter driving the same TE01 window. The gain and efficiency for a single circuit has been optimized using KLSC, a 2 1/2D large signal klystron code. Simulations for a single circuit predict an efficiency of 53% for a single output cavity and 55% for the three cavity output resonator. The total RF output power for this MBK is 55 MW. During the Phase II emphasis will be given to cost reduction techniques resulting in a robust — high efficient — long life high power amplifier.

The North American Regional Climate Change Assessment Program (NARCCAP): Status and results

NASA Astrophysics Data System (ADS)

Arritt, R.

2009-04-01

NARCCAP is an international program that is generating projections of climate change for the U.S., Canada, and northern Mexico at decision-relevant regional scales. NARCCAP uses multiple limited-area regional climate models (RCMs) nested within multiple atmosphere-ocean general circulation models (AOGCMs). The use of multiple regional and global models allows us to investigate the uncertainty in model responses to future emissions (here, the A2 SRES scenario). The project also includes global time-slice experiments at the same discretization (50 km) using the GFDL atmospheric model (AM2.1) and the NCAR atmospheric model (CAM3). Phase I of the experiment uses the regional models nested within reanalysis in order to establish uncertainty attributable to the RCMs themselves. Phase II of the project then nests the RCMs within results from the current and future runs of the AOGCMs to explore the cascade of uncertainty from the global to the regional models. Phase I has been completed and the results to be shown include findings that spectral nudging is beneficial in some regions but not in others. Phase II is nearing completion and some preliminary results will be shown.

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia: Efficacy and Tolerability

PubMed Central

Brown, Patrick; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul

2014-01-01

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials. PMID:24072240

Electronic construction collaboration system -- phase II.

DOT National Transportation Integrated Search

2010-06-01

During the first year of research, work was completed to identify Iowa DOT needs for web-based project management system (WPMS) : and evaluate how commercially available solutions could meet these needs. Researchers also worked to pilot test custom d...

Development of desiccant based air conditioning for hotels and motels. Final report, phase 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banks, N.J.

1994-10-01

This report contains final reports from two phases of field tests: Phase I at the Marriott Courtyard in West Palm Beach, completed in October 1991, and Phase II at the Walt Disney World Swan Hotel in Orlando, completed in August 1993. The goal was to measure the performance and reliability of the desiccant units. The successfull program proved the value of the gas-fired desiccant technology to the hospitality industry. The desiccant units reduced moisture by 15 to 20% relative humidity. Measurements of temperature, humidity, and wallboard moisture content showed a dramatic reduction in the humidity levels experienced prior to installationmore » of the units and in the control areas without desiccants. Moisture damage was kept in check and remodelling due to it was eliminated.« less

Passenger vehicle idling in Vermont, Phase II.

DOT National Transportation Integrated Search

2014-08-01

While trip-start and trip-end idling, including idling at intermediary stops along a route, cannot be completely eliminated, the duration of these discretionary idling events is largely controlled by the driver and can be considered part of travel or...

Practice versus knowledge when it comes to pressure ulcer prevention.

PubMed

Provo, B; Piacentine, L; Dean-Baar, S

1997-09-01

This study was completed to determine the current knowledge and documentation patterns of nursing staff in the prevention of pressure ulcers and to identify the prevalence of pressure ulcers. This pre-post intervention study was carried out in three phases. In phase 1, 67 nursing staff members completed a modified version of Bostrom's Patient Skin Integrity Survey. A Braden Scale score, the presence of actual skin breakdown, and the presence of nursing documentation were collected for each patient (n = 43). Phase II consisted of a 20-minute educational session to all staff. In phase III, 51 nursing staff completed a second questionnaire similar to that completed in phase I. Patient data (n = 49) were again collected using the same procedure as phase I. Twenty-seven staff members completed questionnaires in both phase I and phase III of the study. No statistically significant differences were found in the knowledge of the staff before or after the educational session. The number of patients with a documented plan of care showed a statistically significant difference from phase I to phase III. The number of patients with pressure ulcers or at risk for pressure ulcer development (determined by a Braden Scale score of 16 or less) did not differ statistically from phase I to phase III. Knowledge about pressure ulcers in this sample of staff nurses was for the most part current and consistent with the recommendations in the Agency for Health Care Policy and Research guideline. Documentation of pressure ulcer prevention and treatment improved after the educational session. Although a significant change was noted in documentation, it is unclear whether it reflected an actual change in practice.

Analysis of Class II patients, successfully treated with the straight-wire and Forsus appliances, based on cervical vertebral maturation status.

PubMed

Servello, David F; Fallis, Drew W; Alvetro, Lisa

2015-01-01

To assess skeletal and dental changes in patients successfully treated with the Forsus appliance based on cervical vertebral maturation status. Forty-seven Class II patients, successfully treated with the Forsus appliance, were divided into peak and postpeak growth groups determined immediately prior to Forsus placement. The mean (SD) ages of the peak and postpeak groups were 13.4 (1.0) and 14.1 (1.3) years, respectively. Superimpositions of initial, Forsus placement, Forsus removal, and final cephalometric radiographs were completed, allowing the measurement of changes during three treatment phases. There were no significant differences between groups during treatment phase 1 (alignment/leveling), with both groups demonstrating a worsening of the Class II molar relationship. However, during treatment phase 2 (Class II correction), patients within the peak group demonstrated significantly higher mean apical base, mandibular and molar changes, and an increased rate of change compared with those in the postpeak group. No significant differences were observed during treatment phase 3 (detail/finishing). Following an initial worsening of the Class II molar relationship as a result of straight-wire appliance effects, Forsus appliance treatment initiated during cervical vertebral maturation status (CS) 3-4 elicits more effective and efficient correction of Class II molar relationships than when initiated during CS 5-6. Data support that these effects are due mainly to maxillary skeletal and dentoalveolar restraint during a period of more rapid mandibular growth.

Field testing of hand-held infrared thermography, phase II TPF-5(247) interim report.

DOT National Transportation Integrated Search

2015-12-01

This report describes research completed to develop and implement infrared thermography, a nondestructive evaluation (NDE) : technology for the condition assessment of concrete bridge components. The overall goal of this research was to develop new :...

TRX-4 (TolerRx Inc).

PubMed

Brown, William M

2006-04-01

TolerRx Inc, under license from BTG plc, is developing TRX-4, an anti-CD3 humanized monoclonal antibody for the potential treatment of type 1 diabetes and psoriasis. Phase II trials of the therapeutic antibody in type 1 diabetes have been completed and the company is planning a pivotal phase III trial for this indication. TolerRx is also enrolling psoriasis patients in a phase Ib clinical study of TRX-4. TRX-4 has been awarded Orphan Drug status for recent-onset type 1 diabetes.

A Military-Relevant Model of Closed Concussive Head Injury: Longitudinal Studies Characterizing and Validating Single and Repetitive mTBI

DTIC Science & Technology

2014-10-01

Research Program (CCCRP). Provided in this Year 2 Annual Report are the results of our Phase I studies focused on characterizing the neuropathologic...effects of a single concussive impact to repeated concussive impacts using the PCI model. Phase I studies have been completed and these results set...the foundation for Phase II studies designed to evaluate the effects of repeated concussions that occur prior to and after the resolution of the

Anion Exchange in II-VI Semiconducting Nanostructures via Atomic Templating.

PubMed

Agarwal, Rahul; Krook, Nadia M; Ren, Ming-Liang; Tan, Liang Z; Liu, Wenjing; Rappe, Andrew M; Agarwal, Ritesh

2018-03-14

Controlled chemical transformation of nanostructures is a promising technique to obtain precisely designed novel materials, which are difficult to synthesize otherwise. We report high-temperature vapor-phase anion-exchange reactions to chemically transform II-VI semiconductor nanostructures (100-300 nm length scale) while retaining the single crystallinity, crystal structure, morphology, and even defect distribution of the parent material via atomic templating. The concept of atomic templating is employed to obtain kinetically controlled, thermodynamically metastable structural phases such as zincblende CdSe and CdS from zincblende CdTe upon complete chemical replacement of Te with Se or S. The underlying transformation mechanisms are explained through first-principles density functional theory calculations. Atomic templating is a unique path to independently tune materials' phase and composition at the nanoscale, allowing the synthesis of novel materials.

Human Data Supporting Glyburide in Ischemic Stroke.

PubMed

Sheth, Kevin N; Simard, J Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W Taylor

2016-01-01

The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative.

Assessing critical thinking in medical sciences students in two sequential semesters: Does it improve?

PubMed

Athari, Zeinab-Sadat; Sharif, Sayyed-Mostafa; Nasr, Ahmad Reza; Nematbakhsh, Mehdi

2013-01-01

Critical thinking is an important outcome criterion of higher education in any discipline. Medical and paramedical students always encounter with many new problems in clinical settings and medicinal laboratory, and critical thinking is an essential skill in obtaining a better approach for problem solving. We performed a pre-and post-test to evaluate the change of critical thinking skills in medical sciences students who enrolled in Isfahan University of Medical Sciences in Iran during the academic years 2008-2010. In a longitudinal design study, the critical thinking skills were compared in medical sciences students in two sequential semesters using the California Critical Thinking Skills Test. The test is divided into two parts (parts 1 and 2), including 17 items in each part. Based on proportional stratified sampling, a groups of students (group 1, n=159) were selected from the university population, who enrolled in medicine, pharmacy, nursing, and rehabilitation colleges. The students in group 1 were asked to complete the part 1 of the test (phase I). After one semester, another group (group 2, n=138) from the same population was randomly selected, and they were asked to complete the part two (phase II). The students' demographic data also were recorded. The California critical thinking skills test was translated and it validity and reliability were approved before. No significant difference was observed between the two groups in the demographic data. The students critical thinking scores in phase II significantly reduced in comparison with phase 1 (p<0.05). The phase II scores in subdivisions of analysis, inference, inductive reasoning, and deductive reasoning also failed to demonstrate improvement. It seems curriculum reform is necessary to improve the students' critical thinking.

Development and validation of a brief screening instrument for psychosocial risk associated with genetic testing: a pan-Canadian cohort study

PubMed Central

Esplen, Mary Jane; Cappelli, Mario; Wong, Jiahui; Bottorff, Joan L; Hunter, Jon; Carroll, June; Dorval, Michel; Wilson, Brenda; Allanson, Judith; Semotiuk, Kara; Aronson, Melyssa; Bordeleau, Louise; Charlemagne, Nicole; Meschino, Wendy

2013-01-01

Objectives To develop a brief, reliable and valid instrument to screen psychosocial risk among those who are undergoing genetic testing for Adult-Onset Hereditary Disease (AOHD). Design A prospective two-phase cohort study. Setting 5 genetic testing centres for AOHD, such as cancer, Huntington's disease or haemochromatosis, in ambulatory clinics of tertiary hospitals across Canada. Participants 141 individuals undergoing genetic testing were approached and consented to the instrument development phase of the study (Phase I). The Genetic Psychosocial Risk Instrument (GPRI) developed in Phase I was tested in Phase II for item refinement and validation. A separate cohort of 722 individuals consented to the study, 712 completed the baseline package and 463 completed all follow-up assessments. Most participants were female, at the mid-life stage. Individuals in advanced stages of the illness or with cognitive impairment or a language barrier were excluded. Interventions Phase I: GPRI items were generated from (1) a review of the literature, (2) input from genetic counsellors and (3) phase I participants. Phase II: further item refinement and validation were conducted with a second cohort of participants who completed the GPRI at baseline and were followed for psychological distress 1-month postgenetic testing results. Primary and secondary outcome measures GPRI, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Brief Symptom Inventory (BSI) and Impact of Event Scale (IES). Results The final 20-item GPRI had a high reliability—Cronbach's α at 0.81. The construct validity was supported by high correlations between GPRI and BSI and IES. The predictive value was demonstrated by a receiver operating characteristic curve of 0.78 plotting GPRI against follow-up assessments using HAM-D and HAM-A. Conclusions With a cut-off score of 50, GPRI identified 84% of participants who displayed distress postgenetic testing results, supporting its potential usefulness in a clinical setting. PMID:23485718

Evaluating the accuracy of technicians and pharmacists in checking unit dose medication cassettes.

PubMed

Ambrose, Peter J; Saya, Frank G; Lovett, Larry T; Tan, Sandy; Adams, Dale W; Shane, Rita

2002-06-15

The accuracy rates of board-registered pharmacy technicians and pharmacists in checking unit dose medication cassettes in the inpatient setting at two separate institutions were examined. Cedars-Sinai Medical Center and Long Beach Memorial Medical Center, both in Los Angeles county, petitioned the California State Board of Pharmacy to approve a waiver of the California Code of Regulations to conduct an experimental program to compare the accuracy of unit dose medication cassettes checked by pharmacists with that of cassettes checked by trained, certified pharmacy technicians. The study consisted of three parts: assessing pharmacist baseline checking accuracy (Phase I), developing a technician-training program and certifying technicians who completed the didactic and practical training (Phase II), and evaluating the accuracy of certified technicians checking unit dose medication cassettes as a daily function (Phase III). Twenty-nine pharmacists and 41 technicians (3 of whom were pharmacy interns) participated in the study. Of the technicians, all 41 successfully completed the didactic and practical training, 39 successfully completed the audits and became certified checkers, and 2 (including 1 of the interns) did not complete the certification audits because they were reassigned to another work area or had resigned. In Phase II, the observed accuracy rate and its lower confidence limit exceeded the predetermined minimum requirement of 99.8% for a certified checker. The mean accuracy rates for technicians were identical at the two institutions (p = 1.0). The difference in mean accuracy rates between pharmacists (99.52%; 95% confidence interval [CI] 99.44-99.58%) and technicians, (99.89%; 95% CI 99.87-99.90%) was significant (p < 0.0001). Inpatient technicians who had been trained and certified in a closely supervised program that incorporated quality assurance mechanisms could safely and accurately check unit dose medication cassettes filled by other technicians.

Impact of etanercept tapering on work productivity in patients with early rheumatoid arthritis: results from the PRIZE study

PubMed Central

Zhang, Wei; Bansback, Nick; Sun, Huiying; Pedersen, Ronald; Kotak, Sameer; Anis, Aslam H

2016-01-01

Objective To assess changes in work productivity in patients who have achieved response using etanercept (ETN) 50 mg+methotrexate (MTX) (phase I) are randomised to ETN 25 mg+MTX versus MTX versus placebo (phase II) and then withdrawn from treatment (phase III). Methods Patients included in the analysis were in employment entering phase II of the PRIZE trial and had one or more follow-ups. Phase II was a 39-week, randomised and double-blind comparison of the 3 dose-reduction treatments. Phase III was a 26-week observational study where treatment was withdrawn. The Valuation of Lost Productivity was completed approximately every 13 weeks to estimate productivity impacts from a societal perspective. Results A total of 120 participants were included in our analyses. During phase II, ETN25+MTX or MTX improved paid work productivity by over 100 hours compared with placebo, amounting to a gain of €1752 or €1503, respectively. ETN25+MTX compared with placebo gains €1862 in total paid/unpaid productivity. At week 52, the 3-month paid work productivity loss was 21.8, 12.8 and 14.0 hours, respectively. The productivity loss increased at week 64 from week 52, dropped at week 76 for all treatment groups and then continued rising after week 76 for the placebo group (71.9 hours at week 91) but not for the other 2 groups (21.9 hours for ETX25+MTX and 27.6 hours for MTX). Conclusions The work productivity gain in phase I as a result of ETN50+MTX was marginally lost in the dose-reduction treatment groups, ETN25+MTX and MTX, but substantially lost in the placebo group during phase II. Trial registration number NCT00913458; Results. PMID:27486524

FogEye UV Sensor System Evaluation : Phase II Report

DOT National Transportation Integrated Search

2003-12-01

The primary objective of the FogEye Evaluation Program is to determine whether coupled ultra-violet sources and detectors may provide enhancements to safety on the airport surface. The results of this effort will be used to complete the evaluation of...

Evaluation of Free To Grow, Phase II: Detailed Profile of the Free To Grow Project in California. Final Report.

ERIC Educational Resources Information Center

Harrington, Mary

The Free to Grow pilot project, developed by the Charles R. Drew University of Medicine and Science and its Head Start project, operated between 1994 and 1999. Following a 2-year planning and development stage, 5 project sites went on to complete the 3-year implementation phase in California, Colorado, Kentucky, New York, and Puerto Rico; the…

An Alternative to EPA Method 9 -- Field Validation of the Digital Opacity Compliance System (DOCS)

DTIC Science & Technology

2005-03-15

at the completion of the Phase I and Phase II DOCS field demonstration. These included the following 1) anemometer, 2) sling psychrometer , 3) Abney...anemometer (Eastern Technical Associates, Inc.) Sky conditions Visual observation Relative Humidity Sling Psychrometer (Eastern Technical Associates...least have access to a range of climatic monitoring equipment including the following 1) anemometer, 2) sling psychrometer , 3) Abney Level (sun angle

The Microstructural and Property Changes of Laser Treated Electrodeposits

DTIC Science & Technology

1981-01-01

corresponds to the center of the LASER beam path. Examination of the underlying steel reveals a transformation which appears to be untempered martensite ...specimen after LASER interaction time of 50 ms. Phase transformations have advanced through the complete thickness of the specimen. ii. Hardness plot through...cooling. 13 This technique of achieving homogeneous phase transformations in the surface with sufficient control of surface depth has formed the basis

Daily Goals Formulation and Enhanced Visualization of Mechanical Ventilation Variance Improves Mechanical Ventilation Score.

PubMed

Walsh, Brian K; Smallwood, Craig; Rettig, Jordan; Kacmarek, Robert M; Thompson, John; Arnold, John H

2017-03-01

The systematic implementation of evidence-based practice through the use of guidelines, checklists, and protocols mitigates the risks associated with mechanical ventilation, yet variation in practice remains prevalent. Recent advances in software and hardware have allowed for the development and deployment of an enhanced visualization tool that identifies mechanical ventilation goal variance. Our aim was to assess the utility of daily goal establishment and a computer-aided visualization of variance. This study was composed of 3 phases: a retrospective observational phase (baseline) followed by 2 prospective sequential interventions. Phase I intervention comprised daily goal establishment of mechanical ventilation. Phase II intervention was the setting and monitoring of daily goals of mechanical ventilation with a web-based data visualization system (T3). A single score of mechanical ventilation was developed to evaluate the outcome. The baseline phase evaluated 130 subjects, phase I enrolled 31 subjects, and phase II enrolled 36 subjects. There were no differences in demographic characteristics between cohorts. A total of 171 verbalizations of goals of mechanical ventilation were completed in phase I. The use of T3 increased by 87% from phase I. Mechanical ventilation score improved by 8.4% in phase I and 11.3% in phase II from baseline ( P = .032). The largest effect was in the low risk V T category, with a 40.3% improvement from baseline in phase I, which was maintained at 39% improvement from baseline in phase II ( P = .01). mechanical ventilation score was 9% higher on average in those who survived. Daily goal formation and computer-enhanced visualization of mechanical ventilation variance were associated with an improvement in goal attainment by evidence of an improved mechanical ventilation score. Further research is needed to determine whether improvements in mechanical ventilation score through a targeted, process-oriented intervention will lead to improved patient outcomes. (ClinicalTrials.gov registration NCT02184208.). Copyright © 2017 by Daedalus Enterprises.

Protocol for the ProCare Trial: a phase II randomised controlled trial of shared care for follow-up of men with prostate cancer

PubMed Central

Emery, Jon; Doorey, Juanita; Jefford, Michael; King, Madeleine; Pirotta, Marie; Hayne, Dickon; Martin, Andrew; Trevena, Lyndal; Lim, Tee; Constable, Roger; Hawks, Cynthia; Hyatt, Amelia; Hamid, Akhlil; Violet, John; Gill, Suki; Frydenberg, Mark; Schofield, Penelope

2014-01-01

Introduction Men with prostate cancer require long-term follow-up to monitor disease progression and manage common adverse physical and psychosocial consequences of treatment. There is growing recognition of the potential role of primary care in cancer follow-up. This paper describes the protocol for a phase II multisite randomised controlled trial of a novel model of shared care for the follow-up of men after completing treatment for low-moderate risk prostate cancer. Methods and analysis The intervention is a shared care model of follow-up visits in the first 12 months after completing treatment for prostate cancer with the following specific components: a survivorship care plan, general practitioner (GP) management guidelines, register and recall systems, screening for distress and unmet needs and patient information resources. Eligible men will have completed surgery and/or radiotherapy for low-moderate risk prostate cancer within the previous 8 weeks and have a GP who consents to participate. Ninety men will be randomised to the intervention or current hospital follow-up care. Study outcome measures will be collected at baseline, 3, 6 and 12 months and include anxiety, depression, unmet needs, prostate cancer-specific quality of life and satisfaction with care. Clinical processes and healthcare resource usage will also be measured. The principal emphasis of the analysis will be on obtaining estimates of the treatment effect size and assessing feasibility in order to inform the design of a subsequent phase III trial. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all hospital recruitment sites in Western Australia and Victoria. Results of this phase II trial will be reported in peer-reviewed publications and in conference presentations. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12610000938000 PMID:24604487

Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study.

PubMed

Cohen, Ezra E W; Davis, Darren W; Karrison, Theodore G; Seiwert, Tanguy Y; Wong, Stuart J; Nattam, Sreenivasa; Kozloff, Mark F; Clark, Joseph I; Yan, Duen-Hwa; Liu, Wen; Pierce, Carolyn; Dancey, Janet E; Stenson, Kerstin; Blair, Elizabeth; Dekker, Allison; Vokes, Everett E

2009-03-01

Epidermal growth factor receptor (EGFR) is a validated target in squamous-cell carcinoma of the head and neck, but in patients with recurrent or metastatic disease, EGFR targeting agents have displayed modest efficacy. Vascular endothelial growth factor (VEGF)-mediated angiogenesis has been implicated as a mechanism of resistance to anti-EGFR therapy. In this multi-institutional phase I/II study we combined an EGFR inhibitor, erlotinib, with an anti-VEGF antibody, bevacizumab. Between April 15, 2003, and Jan 27, 2005, patients with recurrent or metastatic squamous-cell carcinoma of the head and neck were enrolled from seven centres in the USA and were given erlotinib (150 mg daily) and bevacizumab in escalating dose cohorts. The primary objectives in the phase I and II sections, respectively, were to establish the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib and to establish the proportion of objective responses and time to disease progression. Pretreatment serum and tissues were collected and analysed by enzyme-linked immunosorbent assay and immunofluorescence quantitative laser analysis, respectively. This study was registered with ClinicalTrials.gov, number NCT00055913. In the phase I section of the trial, ten patients were enrolled in three successive cohorts with no dose-limiting toxic effects noted. 46 patients were enrolled in the phase II section of the trial (including three patients from the phase I section) on the highest dose of bevacizumab (15 mg/kg every 3 weeks). Two additional patients were accrued beyond the protocol-stipulated 46, leaving a total of 48 patients for the phase II assessment. The most common toxic effects of any grade were rash and diarrhoea (41 and 16 of 48 patients, respectively). Three patients had serious bleeding events of grade 3 or higher. Seven patients had a response, with four showing a complete response allowing rejection of the null hypothesis. Median time of overall survival and progression-free survival (PFS) were 7.1 months (95% CI 5.7-9.0) and 4.1 months (2.8-4.4), respectively. Higher ratios of tumour-cell phosphorylated VEGF receptor-2 (pVEGFR2) over total VEGFR2 and endothelial-cell pEGFR over total EGFR in pretreatment biopsies were associated with complete response (0.704 vs 0.386, p=0.036 and 0.949 vs 0.332, p=0.036, respectively) and tumour shrinkage (p=0.007 and p=0.008, respectively) in a subset of 11 patients with available tissue. The combination of erlotinib and bevacizumab is well tolerated in recurrent or metastatic squamous-cell carcinoma of the head and neck. A few patients seem to derive a sustained benefit and complete responses were associated with expression of putative targets in pretreatment tumour tissue.

The Dean and Betty Gallo Prostate Cancer Center

DTIC Science & Technology

2004-07-01

8217 Deleted: Completed 1998), / . Deleted: Clin Cancer Res, 1997 ,phase II study of 13 cis retinoic Completed: Serum TGF- beta and IGF- 30 DiPaola...t , sensitive to activation of both ER alpha and beta . Further laboratory studies by DiPaola and collaborators Deleted: identified additional... Beta -catenin regulates Cripto- and Wnt3- dependent gene expression programs in mouse axis and mesoderm formation. Development, 130: 6283-6294. 2003

JWST Operations and the Phase I and II Process

NASA Astrophysics Data System (ADS)

Beck, Tracy L.

2010-07-01

The JWST operations and Phase I and Phase II process will build upon our knowledge on the current system in use for HST. The primary observing overheads associated with JWST observations, both direct and indirect, are summarized. While some key operations constraints for JWST may cause deviations from the HST model for proposal planning, the overall interface to JWST planning will use the APT and will appear similar to the HST interface. The requirement is to have a proposal planning model simlar to HST, where proposals submitted to the TAC must have at least the minimum amount of information necessary for assessment of the strength of the science. However, a goal of the JWST planning process is to have the submitted Phase I proposal in executable form, and as complete as possible for many programs. JWST will have significant constraints on the spacecraft pointing and orient, so it is beneficial for the planning process to have these scheduling constraints on programs defined as early as possible. The guide field of JWST is also much smaller than the HST guide field, so searches for available guide stars for JWST science programs must be done at the Phase I deadline. The long range observing plan for each JWST cycle will be generated intially from the TAC accepted programs at the Phase I deadline, and the LRP will be refined after the Phase II deadline when all scheduling constraints are defined.

Synthesis and application of surface-imprinted activated carbon sorbent for solid-phase extraction and determination of copper (II)

NASA Astrophysics Data System (ADS)

Li, Zhenhua; Li, Jingwen; Wang, Yanbin; Wei, Yajun

2014-01-01

A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared by a surface imprinting technique for selective solid-phase extraction (SPE) of Cu(II) prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of Cu(II) were optimized with respect to different experimental parameters using static and dynamic procedures in detail. Compared with non-imprinted sorbent, the ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II). The maximum static adsorption capacity of the ion-imprinted and non-imprinted sorbent for Cu(II) was 26.71 and 6.86 mg g-1, respectively. The relatively selectivity factor values (αr) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II) and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted sorbent was carried out using 2 mL of 0.1 mol L-1 EDTA solution. The relative standard deviation of the method was 2.4% for eleven replicate determinations. The method was validated for the analysis by two certified reference materials (GBW 08301, GBW 08303), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace copper in natural water samples with satisfactory results.

Synthesis and application of surface-imprinted activated carbon sorbent for solid-phase extraction and determination of copper (II).

PubMed

Li, Zhenhua; Li, Jingwen; Wang, Yanbin; Wei, Yajun

2014-01-03

A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared by a surface imprinting technique for selective solid-phase extraction (SPE) of Cu(II) prior to its determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of Cu(II) were optimized with respect to different experimental parameters using static and dynamic procedures in detail. Compared with non-imprinted sorbent, the ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II). The maximum static adsorption capacity of the ion-imprinted and non-imprinted sorbent for Cu(II) was 26.71 and 6.86 mg g(-1), respectively. The relatively selectivity factor values (αr) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II) and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted sorbent was carried out using 2 mL of 0.1 mol L(-1) EDTA solution. The relative standard deviation of the method was 2.4% for eleven replicate determinations. The method was validated for the analysis by two certified reference materials (GBW 08301, GBW 08303), the results obtained is in good agreement with standard values. The developed method was also successfully applied to the determination of trace copper in natural water samples with satisfactory results. Copyright © 2013 Elsevier B.V. All rights reserved.

California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS).

PubMed

Stone, William S; Mesholam-Gately, Raquelle I; Braff, David L; Calkins, Monica E; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Seidman, Larry J

2015-04-01

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. Copyright © 2014. Published by Elsevier B.V.

California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: Comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS)

PubMed Central

Stone, William S.; Mesholam-Gately, Raquelle I.; Braff, David L.; Calkins, Monica E.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Seidman, Larry J.

2018-01-01

The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded “milder” SZ phenotypes than those acquired subsequently in the COGS-2 case–control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. PMID:25497440

Antibody for the prevention of neonatal noscocomial staphylococcal infection: a review of the literature.

PubMed

Weisman, L E

2007-09-01

Staphylococci, especially coagulase negative staphylococci (CONS), are responsible for over 75 % of late-onset infections in very low birth weight infants. These infections cause increased length of hospital stay, need for antibiotics, and cost of medical care. Several drug companies have developed and evaluated hyperimmune polyclonal and monoclonal antibodies for the prevention of neonatal staphylococcal infection including 1) Altastaph by North American Biologics Inc., 2) Veronate by Inhibitex Inc., and 3) Pagibaximab by Biosynexus Inc, and Glaxo Smith Kline Inc. We will review the development and status of these potential products. Altastaph is a S. aureus serotype 5 and 8 vaccine induced hyperimmune polyclonal antibody whose development has been placed on hold due to its failure to demonstrate any trend toward efficacy in a recently completed Phase II study. Veronate is a polyclonal antibody obtained by plasmapheresis from donors with high titers of MSCRAMM (microbial surface components recognizing adhesion matrix molecules) activity against CONS whose development has been placed on hold due to its failure to demonstrate effectiveness in a recently completed Phase III study. Pagibaximab is a humanized mouse chimeric monoclonal antibody (previously known as BSYX-A110) directed against lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, that has recently completed a Phase II study suggesting efficacy and is being developed further for clinical investigation.

The influence of Ni(II) on brushite structure stabilization

NASA Astrophysics Data System (ADS)

Guerra-López, J. R.; Güida, J. A.; Ramos, M. A.; Punte, G.

2017-06-01

Brushite samples doped with Ni(II) in different concentrations, from 5% to 20%, were prepared in aqueous solution at pH = 7 and at two temperatures: 25 and 37 °C. The solid samples were characterized by chemical analysis, infrared spectroscopy (FTIR) and x-ray powder diffraction (XRPD). Chemical analysis has shown Ni(II) almost complete incorporation to the solid phase up to 15%. X-ray diffraction patterns have allowed to identify brushite phase with almost no modification of the line breadth and only small shifts of lines positions with increasing Ni(II) incorporation up to 15%. For larger Ni(II) concentration, in solution, a mixture of phases has been detected. Infrared spectra have supported diffraction results. For Ni(II) 20% and over the characteristic bands of HPO42- anions tend to vanish, and the typical shaped PO43- bands are observed. These results have allowed to establish that the presence of low levels of Ni in the synthetic process not only helps brushite formation; but, also prevents brushite from apatite conversion and, in addition, preserves brushite crystallinity. According to these findings, it is possible to propose that nickel traces present in the urinary system might be a trigger to brushite stone formation and/or growth, rather than the expected brushite conversion to hydroxyapatite. This outcome would explain the recurrent detection of difficult to treat brushite stones, observed in the last three decades.

DEVELOPING A COST EFFECTIVE ENVIRONMENTAL SOLUTION FOR PRODUCED WATER AND CREATING A ''NEW'' WATER RESOURCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glenn Doran

1997-04-28

This report summarizes the status of this project for the quarter January 1, 1997 to March 31, 1997. Phase II has been started and Task 7, Develop Pilot Scale Test Work Plan has been completed. The operational portion of this phase, Task 8 has been initiated with several pieces of pilot equipment already on-site. The start up of the full process train will not occur until the next quarter. The project is slightly behind schedule. A no cost extension was requested and was granted. The anticipated completion date is December 31, 1997. The project is on budget.

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

PubMed

Wiernik, P H; Gordon, L I; Oken, M M; Harris, J E; O'Connell, M J

1999-10-01

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

TECHNOLOGY FOR ENHANCED BIODIESEL ECONOMICS - PHASE II

EPA Science Inventory

The overall goal of this project is to complete the research and development of an innovative process technology to enhance the economics of biodiesel production, through upgrading the byproduct glycerol to a propane fuel (LPG), which (a) is widely used today, (b) has an exist...

Guideline-based intervention to reduce telemetry rates in a large tertiary centre.

PubMed

Ramkumar, Satish; Tsoi, Edward H; Raghunath, Ajay; Dias, Floyd F; Li Wai Suen, Christopher; Tsoi, Andrew H; Mansfield, Darren R

2017-07-01

Inappropriate cardiac telemetry use is associated with reduced patient flow and increased healthcare costs. To evaluate the outcomes of guideline-based application of cardiac telemetry. Phase I involved a prospective audit (March to August 2011) of telemetry use at a tertiary hospital. Data were collected on indication for telemetry and clinical outcomes. Phase II prospectively included patients more than 18 years under general medicine requiring ward-based telemetry. As phase II occurred at a time remotely from phase I, an audit similar to phase I (phase II - baseline) was completed prior to a 3-month intervention (May to August 2015). The intervention consisted of a daily telemetry ward round and an admission form based on the American Heart Association guidelines (class I, telemetry indicated; class II, telemetry maybe indicated; class III, telemetry not indicated). Patient demographics, telemetry data, and clinical outcomes were studied. Primary endpoint was the percentage reduction of class III indications, while secondary endpoint included telemetry duration. In phase I (n = 200), 38% were admitted with a class III indication resulting in no change in clinical management. A total of 74 patients was included in phase II baseline (mean ± standard deviation (SD) age 73 years ± 14.9, 57% male), whilst 65 patients were included in the intervention (mean ± SD age 71 years ± 18.4, 35% male). Both groups had similar baseline characteristics. There was a reduction in class III admissions post-intervention from 38% to 11%, P < 0.001. Intervention was associated with a reduction in median telemetry duration (1.8 ± 1.8 vs 2.4 ± 2.5 days, P = 0.047); however, length of stay was similar in both groups (P > 0.05). Guideline-based telemetry admissions and a regular telemetry ward round are associated with a reduction in inappropriate telemetry use. © 2017 Royal Australasian College of Physicians.

INDEPENDENT REVIEW OF THE X-701B GROUNDWATER REMEDY, PORTSMOUTH, OHIO: TECHNICAL EVALUATION AND RECOMMENDATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looney, B.; Eddy-Dilek, C.; Costanza, J.

2008-12-15

The Department of Energy Portsmouth Paducah Project Office requested assistance from Department of Energy Office of Environmental Management (EM-22) to provide independent technical experts to evaluate past and ongoing remedial activities at the Portsmouth facility that were completed to address TCE contamination associated with the X-701B groundwater plume and to make recommendations for future efforts. The Independent Technical Review team was provided with a detailed and specific charter. The charter requested that the technical team first review the past and current activities completed for the X-701B groundwater remedy for trichloroethene (TCE) in accordance with a Decision Document that was issuedmore » by Ohio EPA on December 8, 2003 and a Work Plan that was approved by Ohio EPA on September 22, 2006. The remedy for X-701B divides the activities into four phases: Phase I - Initial Source Area Treatment, Phase II - Expanded Source Area Treatment, Phase III - Evaluation and Reporting, and Phase IV - Downgradient Remediation and Confirmation of Source Area Treatment. Phase I of the remedy was completed during FY2006, and DOE has now completed six oxidant injection events within Phase II. The Independent Technical Review team was asked to evaluate Phase II activities, including soil and groundwater results, and to determine whether or not the criteria that were defined in the Work Plan for the Phase II end point had been met. The following criteria are defined in the Work Plan as an acceptable Phase II end point: (1) Groundwater samples from the identified source area monitoring wells have concentrations below the Preliminary Remediation Goal (PRG) for TCE in groundwater, or (2) The remedy is no longer effective in removing TCE mass from the source area. In addition, the charter specifies that if the Review Team determines that the Phase II endpoint has not been reached, then the team should address the following issues: (1) If additional injection events are recommended, the team should identify the type of injection and target soil horizon for these injections; (2) Consider the feasibility of declaring Technical Impracticability and proceeding with the RCRA Cap for the X-701B; and (3) Provide a summary of other cost-effective technologies that could be implemented (especially for the lower Gallia). The Independent Technical Review team focused its evaluation solely on the X-701B source zone and contaminant plume. It did not review current or planned remedial activities at other plumes, waste areas, or landfills at the Portsmouth site, nor did it attempt to integrate such activities into its recommendations for X-701B. However, the ultimate selection of a remedy for X-701B by site personnel and regulators should take into account potentially synergistic efforts at other waste areas. Assessment of remedial alternatives in the context of site-wide management practices may reveal opportunities for leveraging and savings that would not otherwise be identified. For example, the cost of source-zone excavation or construction of a permeable reactive barrier at X-701B might be substantially reduced if contaminated soil could be buried on site at an existing or planned landfill. This allowance would improve the feasibility and competitiveness of both remedies. A comprehensive examination of ongoing and future environmental activities across the Portsmouth Gaseous Diffusion Plant is necessary to optimize the selection and timing of X-701B remediation with respect to cleanup efficiency, safety, and economics. A selected group of technical experts attended the technical workshop at the Portsmouth Gaseous Diffusion Plant from November 18 through 21, 2008. During the first day of the workshop, both contractor and DOE site personnel briefed the workshop participants and took them on a tour of the X-701B site. The initial briefing was attended by representatives of Ohio EPA who participated in the discussions. On subsequent days, the team reviewed baseline data and reports, were provided additional technical information from site personnel, evaluated work plans, determined critical issues and uncertainties, and recommended alternatives. This report documents the findings and recommendations of the independent technical review team.« less

Summary Report on Phase I and Phase II Results From the 3D Printing in Zero-G Technology Demonstration Mission. Volume II

NASA Technical Reports Server (NTRS)

Prater, T. J.; Werkheiser, N. J.; Ledbetter, F. E., III

2018-01-01

In-space manufacturing seeks to develop the processes, skill sets, and certification architecture needed to provide a rapid response manufacturing capability on long-duration exploration missions. The first 3D printer on the Space Station was developed by Made in Space, Inc. and completed two rounds of operation on orbit as part of the 3D Printing in Zero-G Technology Demonstration Mission. This Technical Publication provides a comprehensive overview of the technical objections of the mission, the two phases of hardware operation conducted on orbit, and the subsequent detailed analysis of specimens produced. No engineering significant evidence of microgravity effects on material outcomes was noted. This technology demonstration mission represents the first step in developing a suite of manufacturing capabilities to meet future mission needs.

Standards Improvement Project-Phase II. Final rule.

PubMed

2005-01-05

The Occupational Safety and Health Administration (OSHA) through this final rule is continuing to remove and revise provisions of its standards that are outdated, duplicative, unnecessary, or inconsistent, or can be clarified or simplified by being written in plain language. The Agency completed Phase I of the Standards Improvement Project in June 1998. In this Phase II of the Standards Improvement Project, OSHA is again revising or removing a number of health provisions in its standards for general industry, shipyard employment, and construction. The Agency believes that the changes streamline and make more consistent the regulatory requirements in OSHA health and safety standards. In some cases, OSHA has made substantive revisions to requirements because they are outdated, duplicative, unnecessary, or inconsistent with more recently promulgated health standards. The Agency believes these revisions will reduce regulatory requirements for employers without reducing employee protection.

Conformational polymorphism and thermochemical analysis of 5,5' ''-bis[(2,2,5,5-tetramethyl-1-aza-2,5-disila-1-cyclopentyl)ethyl]-2,2':5',2' ':5' ',2' ''-quaterthiophene.

PubMed

Muguruma, Hitoshi; Hotta, Shu

2006-11-23

The titled compound exists as two polymorphic solid phases (denoted form-I and form-II). Form-I obtained by as-synthesized material is a more stable phase. Form-II is a less stable phase. Spontaneous solid-solid transformation from form-II to form-I is observed in the temperature range between room temperature and the melting point of form-I (Tm = 156.5 degrees C), and its activation energy is estimated to be 96 kJ mol-1 by Arrhenius plot. The solid-solute-solid transformation (recrystallization from solution) from form-II to form-I is also observed. In contrast, form-II is obtained only by a solid-melt-solid transformation from form-I. Therefore, the system of two polymorphs is monotropic. The solid-state NMR measurement shows that form-I has the molecular conformation of complete S-syn-anti-syn in the oligothiophene backbone, whereas form-II has that of S-all-anti. With the solution NMR data, the polymorphism could not be observed. Therefore, the polymorphs originate from the different molecular packing involving the conformational change of the molecule. This unique property is attributed to the extra bulky terminal groups of the compounds. However, despite the extra bulky terminal groups, the mentioned polymorphism is not observed in the titled compound analogue which has S-all-anti conformation (like form-II).

Anti-MRSA beta-lactams in development.

PubMed

Page, Malcolm G P

2006-10-01

Ceftobiprole medocaril, the most advanced of the anti-MRSA (methicillin-resistant Staphylococcus aureus) beta-lactams in clinical development, has recently completed its first Phase III clinical trial, and has demonstrated non-inferiority to vancomycin. Phase II clinical trials have been initiated with PPI0903, which is, like ceftobiprole medocaril, an injectable pro-drug of a broad-spectrum cephalosporin with anti-MRSA activity, and with RO4908643, a carbapenem with more modest activity against MRSA.

Chemically-modified activated carbon with ethylenediamine for selective solid-phase extraction and preconcentration of metal ions.

PubMed

Li, Zhenhua; Chang, Xijun; Zou, Xiaojun; Zhu, Xiangbing; Nie, Rong; Hu, Zheng; Li, Ruijun

2009-01-26

A new method that utilizes ethylenediamine-modified activated carbon (AC-EDA) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES). The new sorbent was prepared by oxidative surface modification. Experimental conditions for effective adsorption of trace levels of Cr(III), Fe(III), Hg(II) and Pb(II) were optimized with respect to different experimental parameters using batch and column procedures in detail. The optimum pH value for the separation of metal ions simultaneously on the new sorbent was 4.0. Complete elution of absorbed metal ions from the sorbent surface was carried out using 3.0 mL of 2% (%w/w) thiourea and 0.5 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation and determination of target metal ions. The maximum static adsorption capacity of the sorbent at optimum conditions was found to be 39.4, 28.9, 60.5 and 49.9 mg g(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The time for 94% adsorption of target metal ions was less than 2 min. The detection limits of the method was found to be 0.28, 0.22, 0.09 and 0.17 ng mL(-1) for Cr(III), Fe(III), Hg(II) and Pb(II), respectively. The precision (R.S.D.) of the method was lower 4.0% (n=8). The prepared sorbent as solid-phase extractant was successfully applied for the preconcentration of trace Cr(III), Fe(III), Hg(II) and Pb(II) in natural and certified samples with satisfactory results.

The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis).

PubMed

Meinking, Terri L; Villar, Maria E; Vicaria, Maureen; Eyerdam, Debbie H; Paquet, Diane; Mertz-Rivera, Kamara; Rivera, Hector F; Hiriart, Javier; Reyna, Susan

2010-01-01

Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods.

PubMed

Weiland, S K; Björkstén, B; Brunekreef, B; Cookson, W O C; von Mutius, E; Strachan, D P

2004-09-01

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.

A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109.

PubMed

Van Veldhuizen, Peter J; Faulkner, James R; Lara, Primo N; Gumerlock, Paul H; Goodwin, J Wendall; Dakhil, Shaker R; Gross, Howard M; Flanigan, Robert C; Crawford, E David

2005-07-01

Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen. A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks. Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each). Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.

Pharmacokinetic interplay of phase II metabolism and transport: a theoretical study.

PubMed

Wu, Baojian

2012-01-01

Understanding of the interdependence of cytochrome P450 enzymes and P-glycoprotein in disposition of drugs (also termed "transport-metabolism interplay") has been significantly advanced in recent years. However, whether such "interplay" exists between phase II metabolic enzymes and efflux transporters remains largely unknown. The objective of this article is to explore the role of efflux transporters (acting on the phase II metabolites) in disposition of the parent drug in Caco-2 cells, liver, and intestine via simulations utilizing a catenary model (for Caco-2 system) and physiologically based pharmacokinetic (PBPK) models (for the liver and intestine). In all three models, "transport-metabolism interplay" (i.e., inhibition of metabolite efflux decreases the metabolism) can be observed only when futile recycling (or deconjugation) occurred. Futile recycling appeared to bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof. Without futile recycling, metabolite formation was independent on its downstream process excretion, thus impact of metabolite excretion on its formation was impossible. Moreover, in liver PBPK model with futile recycling, impact of biliary metabolite excretion on the exposure of parent drug [(systemic (reservoir) area under the concentration-time curve (AUC(R1))] was limited; a complete inhibition of efflux resulted in AUC(R1) increases of less than 1-fold only. In intestine PBPK model with futile recycling, even though a complete inhibition of efflux could result in large elevations (e.g., 3.5-6.0-fold) in AUC(R1), an incomplete inhibition of efflux (e.g., with a residual activity of ≥ 20% metabolic clearance) saw negligible increases (<0.9-fold) in AUC(R1). In conclusion, this study presented mechanistic observations of pharmacokinetic interplay between phase II enzymes and efflux transporters. Those studying such "interplay" are encouraged to adequately consider potential consequences of inhibition of efflux transporters in humans. Copyright © 2011 Wiley-Liss, Inc.

Status report of the Gerda Phase II startup

NASA Astrophysics Data System (ADS)

D'Andrea, Valerio; Gerda Collaboration

2017-01-01

The GERmanium Detector Array (GERDA) experiment, located at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN, searches for 0νββ of 76Ge . Germanium diodes enriched to ˜ 86 % in the double beta emitter 76Ge ( enrGe are exposed being both source and detector of 0νββ decay. This process is considered a powerful probe to address still open issues in the neutrino sector of the (beyond) Standard Model of particle Physics. Since 2013, at the completion of the first experimental phase (Phase I), the GERDA setup has been upgraded to perform its next step (Phase II). The aim is to reach a sensitivity to the 0νββ decay half-life larger than 10^{26} yr in about 3 years of physics data taking, exposing a detector mass of about 35 kg of enrGe with a background index of about 10^{-3} cts/(keV . kg . yr). One of the main new implementations is the liquid argon (LAr) scintillation light read-out, to veto those events that only partially deposit their energy both in Ge and in the surrounding LAr. In this paper the GERDA Phase II expected goals, the upgraded items and few selected features from the first 2016 physics and calibration runs will be presented. The main Phase I achievements will be also reviewed.

75 FR 46942 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

... employers. Should any needed methodological changes be identified, NIOSH will submit a request for modification to OMB. If no substantive methodological changes are required, the phase II study will proceed and... complete the questionnaire on the web or by telephone at that time.) Assuming no methodological changes...

Long term evaluation of characteristics in an artificial Northern California vernal pool system.

DOT National Transportation Integrated Search

2003-04-01

This report (Phase II) completes an evaluation of 3 sets of 5 artificial vernal pools located on Travis AFB in Solano County CA. The research was done to determine if artificial vernal pools constructed on Travis AFB in 1993 maintained vernal pool ch...

40 CFR 75.4 - Compliance dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

....e., SO2 or NOX, as applicable): (A) Only if the relative accuracy test audit (RATA) of the high... that all certification tests are completed no later than the following dates (except as provided in... an oil-fired Phase II unit, January 1, 1995, except that installation and certification tests for...

Central State University: Phase II Report

ERIC Educational Resources Information Center

Ohio Board of Regents, 2012

2012-01-01

In accordance with Ohio Amended Substitute House Bill 153, the Chancellor submitted to the state Legislature and the Governor a plan, developed in consultation with Central State University, that assures the Central State Supplement will be used to promote the goals of increasing enrollment, improving course completion, and increasing the number…

Searching for a dark photon with DarkLight

DOE PAGES

Corliss, R.

2016-07-30

Here, we describe the current status of the DarkLight experiment at Jefferson Laboratory. DarkLight is motivated by the possibility that a dark photon in the mass range 10 to 100 MeV/c 2 could couple the dark sector to the Standard Model. DarkLight will precisely measure electron proton scattering using the 100 MeV electron beam of intensity 5 mA at the Jefferson Laboratory energy recovering linac incident on a windowless gas target of molecular hydrogen. We will detect the complete final state including scattered electron, recoil proton, and e +e - pair. A phase-I experiment has been funded and is expectedmore » to take data in the next eighteen months. The complete phase-II experiment is under final design and could run within two years after phase-I is completed. The DarkLight experiment drives development of new technology for beam, target, and detector and provides a new means to carry out electron scattering experiments at low momentum transfers.« less

Production, characterization and operation of Ge enriched BEGe detectors in GERDA

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Andreotti, E.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Barros, N.; Baudis, L.; Bauer, C.; Becerici-Schmidt, N.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Budjáš, D.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Domula, A.; Egorov, V.; Falkenstein, R.; Freund, K.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gotti, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hegai, A.; Heisel, M.; Hemmer, S.; Heusser, G.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Ioannucci, L.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Klimenko, A.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Misiaszek, M.; Nemchenok, I.; Nisi, S.; O'Shaughnessy, C.; Palioselitis, D.; Pandola, L.; Pelczar, K.; Pessina, G.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salathe, M.; Schmitt, C.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Schönert, S.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Strecker, H.; Ur, C. A.; Vanhoefer, L.; Vasenko, A. A.; von Sturm, K.; Wagner, V.; Walter, M.; Wegmann, A.; Wester, T.; Wilsenach, H.; Wojcik, M.; Yanovich, E.; Zavarise, P.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2015-02-01

The GERmanium Detector Array ( Gerda) at the Gran Sasso Underground Laboratory (LNGS) searches for the neutrinoless double beta decay () of Ge. Germanium detectors made of material with an enriched Ge fraction act simultaneously as sources and detectors for this decay. During Phase I of theexperiment mainly refurbished semi-coaxial Ge detectors from former experiments were used. For the upcoming Phase II, 30 new Ge enriched detectors of broad energy germanium (BEGe)-type were produced. A subgroup of these detectors has already been deployed in Gerda during Phase I. The present paper reviews the complete production chain of these BEGe detectors including isotopic enrichment, purification, crystal growth and diode production. The efforts in optimizing the mass yield and in minimizing the exposure of the Ge enriched germanium to cosmic radiation during processing are described. Furthermore, characterization measurements in vacuum cryostats of the first subgroup of seven BEGe detectors and their long-term behavior in liquid argon are discussed. The detector performance fulfills the requirements needed for the physics goals of Gerda Phase II.

High Voltage, Solid-State Switch for Fusion Science Applications

NASA Astrophysics Data System (ADS)

Ziemba, Timothy; Prager, James; Miller, Kenneth E.; Slobodov, Ilia

2017-10-01

Eagle Harbor Technologies, Inc. is developing a series stack of solid-state switches to produce a single high voltage switch that can be operated at over 35 kV. During the Phase I program, EHT developed two high voltage switch modules: one with isolated power gate drive and a second with inductively coupled gate drive. These switches were tested at 15 kV and up to 300 A at switching frequencies up to 500 kHz for 10 ms bursts. Robust switching was demonstrated for both IGBTs and SiC MOSFETs. During the Phase II program, EHT will develop a higher voltage switch (>35 kV) that will be suitable for high pulsed and average power applications. EHT will work with LTX to utilize these switches to design, build, and test a pulsed magnetron driver that will be delivered to LTX before the completion of the program. EHT will present data from the Phase I program as well as preliminary results from the start of the Phase II program. With support of DOE SBIR.

BPM Design and Impedance Considerations for a Rotatable Collimator for the LHC Collimation Upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Jeffrey Claiborne; /SLAC; Keller, Lewis

2010-08-26

The Phase II upgrade to the LHC collimation system calls for complementing the 30 high robust Phase I graphite secondary collimators with 30 high Z Phase II collimators. This paper reports on BPM and impedance considerations and measurements of the integrated BPMs in the prototype rotatable collimator to be installed in the Super Proton Synchrotron (SPS) at CERN. The BPMs are necessary to align the jaws with the beam. Without careful design the beam impedance can result in unacceptable heating of the chamber wall or beam instabilities. The impedance measurements involve utilizing both a single displaced wire and two wiresmore » excited in opposite phase to disentangle the driving and detuning transverse impedances. Trapped mode resonances and longitudinal impedance are to also be measured and compared with simulations. These measurements, when completed, will demonstrate the device is fully operational and has the impedance characteristics and BPM performance acceptable for installation in the SPS.« less

A Personal Computer-Based Head-Spine Model

DTIC Science & Technology

1998-09-01

the CHSM. CHSM was comprised of the pelvis, the thoracolumbar spine, a single beam representation of the cervical spine, the head, the rib cage , and...developing the private sector HSM-PC project follows the Phase II program Work Plan , but continues into a Phase m SBIR program internally funded by...on completing the head and neck portion of HSM-PC, which as described in the Confidence Assessment Plan (CA Plan ) will be known as the Head Cervical

Evaluation of Hands-Free Devices for Space Habitat Maintenance Procedures

NASA Technical Reports Server (NTRS)

Hoffman, R. B.; Twyford, E.; Conlee, C. S.; Litaker, H. L.; Solemn, J. A.; Holden

2007-01-01

Currently, International Space Station (ISS) crews use a laptop computer to display procedures for performing onboard maintenance tasks. This approach has been determined to be suboptimal. A heuristic evaluation and two studies have been completed to test commercial off-the-shelf (COTS) "near-eye" heads up displays (HUDs) for support of these types of maintenance tasks. In both studies, subjects worked through electronic procedures to perform simple maintenance tasks. As a result of the Phase I study, three HUDs were down-selected to one. In the Phase II study, the HUD was compared against two other electronic display devices - a laptop computer and an e-book reader. Results suggested that adjustability and stability of the HUD display were the most significant acceptability factors to consider for near-eye displays. The Phase II study uncovered a number of advantages and disadvantages of the HUD relative to the laptop and e-book reader for interacting with electronic procedures.

Surface reaction of SnII on goethite (α-FeOOH): surface complexation, redox reaction, reductive dissolution, and phase transformation.

PubMed

Dulnee, Siriwan; Scheinost, Andreas C

2014-08-19

To elucidate the potential risk of (126)Sn migration from nuclear waste repositories, we investigated the surface reactions of Sn(II) on goethite as a function of pH and Sn(II) loading under anoxic condition with O2 level < 2 ppmv. Tin redox state and surface structure were investigated by Sn K edge X-ray absorption spectroscopy (XAS), goethite phase transformations were investigated by high-resolution transmission electron microscopy and selected area electron diffraction. The results demonstrate the rapid and complete oxidation of Sn(II) by goethite and formation of Sn(IV) (1)E and (2)C surface complexes. The contribution of (2)C complexes increases with Sn loading. The Sn(II) oxidation leads to a quantitative release of Fe(II) from goethite at low pH, and to the precipitation of magnetite at higher pH. To predict Sn sorption, we applied surface complexation modeling using the charge distribution multisite complexation approach and the XAS-derived surface complexes. Log K values of 15.5 ± 1.4 for the (1)E complex and 19.2 ± 0.6 for the (2)C complex consistently predict Sn sorption across pH 2-12 and for two different Sn loadings and confirm the strong retention of Sn(II) even under anoxic conditions.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Research and Operational Support for the Study of Military Relevant Infectious Diseases of Interest to United States and Royal Thai Government

DTIC Science & Technology

2006-01-01

in progress 8 PvDBP Polymorphisms Study completed; publication in progress 9 Tafenoquine Cure /Radical Cure Dose Ranging NIH In life completed Jan...and II, as possibly phase III testing. We will continue efforts for tafenoquine development, especially towards an indication of radical cure for...disease (prophylaxis) and to cure the infection (therapeutic). Antimalarial drug screening in the rhesus monkey model is very effective for making

Special Inspector General for Iraq Reconstruction (SIGIR): The Year of Transition in Review

DTIC Science & Technology

2007-01-30

border forts have been constructed thus far, and 5 points of entry have been completed.315 SIGIR’s ground project surveys inspected 21 border forts and...Gen. Dempsey recently estimated that 20-25% of the National Police “needed to be weeded out.”367 Finally, recent surveys suggest that public...Transportation and Communications system, 33 site surveys have been completed for the communication towers between Mosul and Basrah.409 Phase II

Internally Actuated Lateral-Directional Maneuvering for a Blended Wing-Body Underwater Glider

DTIC Science & Technology

2009-04-01

Techy , as a PhD student in aerospace engineering. PHASE I & II WORK COMPLETED Completed work is presented in terms of the three major tasks: modeling...asymptotically stabilizes streamlined translation of a conventional AUV in any desired inertial direction. More recently Woolsey [2006] and Woolsey and Techy ...on Decision and Control, pp. 6826-6831, San Diego, CA, December 2006 (Invited paper.) Woolsey, C. A. and L. Techy . "Cross-track control of a slender

The GERDA experiment: results and perspectives

NASA Astrophysics Data System (ADS)

Macolino, Carla; Gerda Collaboration

2014-11-01

The Germanium Detector Array, GERDA, at Laboratori Nazionali del Gran Sasso (Italy), is designed to search for Majorana neutrinos via neutrinoless double beta (0νββ) decay of 76Ge. GERDA completed the Phase I in 2013, after an exposure of 21.6 kg·yr and with a background of about 0.01 cts/(keVkgyr): no signal was found and a limit on the half-life of T0ν1/2 > 2.1 · 1025 yr (90% C.L.) was established. The previous claim of 0νββ observation for 76Ge is strongly disfavoured in a model independent way. The commission for GERDA Phase II is currently ongoing and about 20 kg of additional enriched Ge diodes will be deployed. Pulse- shape analysis, together with the liquid argon instrumentation will allow to reach a background level one order of magnitude lower than in Phase I. In this paper the measurement of the half-life of 0νββ decay from GERDA Phase I and the expected sensitivity for Phase II are discussed.

Practical implementation of the double linear damage rule and damage curve approach for treating cumulative fatigue damage

NASA Technical Reports Server (NTRS)

Manson, S. S.; Halford, G. R.

1981-01-01

Simple procedures are given for treating cumulative fatigue damage under complex loading history using either the damage curve concept or the double linear damage rule. A single equation is given for use with the damage curve approach; each loading event providing a fraction of damage until failure is presumed to occur when the damage sum becomes unity. For the double linear damage rule, analytical expressions are given for determining the two phases of life. The procedure comprises two steps, each similar to the conventional application of the commonly used linear damage rule. Once the sum of cycle ratios based on Phase I lives reaches unity, Phase I is presumed complete, and further loadings are summed as cycle ratios based on Phase II lives. When the Phase II sum attains unity, failure is presumed to occur. It is noted that no physical properties or material constants other than those normally used in a conventional linear damage rule analysis are required for application of either of the two cumulative damage methods described. Illustrations and comparisons are discussed for both methods.

Phase structure of one-dimensional interacting Floquet systems. II. Symmetry-broken phases

NASA Astrophysics Data System (ADS)

von Keyserlingk, C. W.; Sondhi, S. L.

2016-06-01

Recent work suggests that a sharp definition of "phase of matter" can be given for periodically driven "Floquet" quantum systems exhibiting many-body localization. In this work, we propose a classification of the phases of interacting Floquet localized systems with (completely) spontaneously broken symmetries; we focus on the one-dimensional case, but our results appear to generalize to higher dimensions. We find that the different Floquet phases correspond to elements of Z (G ) , the center of the symmetry group in question. In a previous paper [C. W. von Keyserlingk and S. L. Sondhi, preceding paper, Phys. Rev. B 93, 245145 (2016)], 10.1103/PhysRevB.93.245145, we offered a companion classification of unbroken, i.e., paramagnetic phases.

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

PubMed

Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

2018-06-01

Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018 Elsevier Inc. All rights reserved.

An integrated bioremediation process for petroleum hydrocarbons removal and odor mitigation from contaminated marine sediment.

PubMed

Zhang, Zhen; Lo, Irene M C; Yan, Dickson Y S

2015-10-15

This study developed a novel integrated bioremediation process for the removal of petroleum hydrocarbons and the mitigation of odor induced by reduced sulfur from contaminated marine sediment. The bioremediation process consisted of two phases. In Phase I, acetate was dosed into the sediment as co-substrate to facilitate the sulfate reduction process. Meanwhile, akaganeite (β-FeOOH) was dosed in the surface layer of the sediment to prevent S(2-) release into the overlying seawater. In Phase II, NO3(-) was injected into the sediment as an electron acceptor to facilitate the denitrification process. After 20 weeks of treatment, the sequential integration of the sulfate reduction and denitrification processes led to effective biodegradation of total petroleum hydrocarbons (TPH), in which about 72% of TPH was removed. In Phase I, the release of S(2-) was effectively controlled by the addition of akaganeite. The oxidation of S(2-) by Fe(3+) and the precipitation of S(2-) by Fe(2+) were the main mechanisms for S(2-) removal. In Phase II, the injection of NO3(-) completely inhibited the sulfate reduction process. Most of residual AVS and S(0) were removed within 4 weeks after NO3(-) injection. The 16S rRNA clone library-based analysis revealed a distinct shift of bacterial community structure in the sediment over different treatment phases. The clones affiliated with Desulfobacterales and Desulfuromonadales were the most abundant in Phase I, while the clones related to Thioalkalivibrio sulfidophilus, Thiohalomonas nitratireducens and Sulfurimonas denitrificans predominated in Phase II. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

PubMed

Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

2017-09-01

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine ({sup 131}I) metuximab injection: Clinical Phase I/II trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Zhinan; Mi Li; Xu Jing

2006-06-01

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ({sup 131}I) metuximab injection (Licartin), a novel {sup 131}I-labeled HAb18G/CD147-specific monoclonal antibody F(ab'){sub 2} fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxicmore » effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p 0.0019). Conclusion: Iodine ({sup 131}I) metuximab injection is safe and active for HCC patients.« less

PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert Calderon

2003-04-28

This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was successfully completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron or steel consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy.

PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert Calderon

2003-01-28

This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was successfully completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron or steel consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy.

The conversion process of hydrocarbon hydrates into CO2 hydrates and vice versa: thermodynamic considerations.

PubMed

Schicks, J M; Luzi, M; Beeskow-Strauch, B

2011-11-24

Microscopy, confocal Raman spectroscopy and powder X-ray diffraction (PXRD) were used for in situ investigations of the CO(2)-hydrocarbon exchange process in gas hydrates and its driving forces. The study comprises the exposure of simple structure I CH(4) hydrate and mixed structure II CH(4)-C(2)H(6) and CH(4)-C(3)H(8) hydrates to gaseous CO(2) as well as the reverse reaction, i.e., the conversion of CO(2)-rich structure I hydrate into structure II mixed hydrate. In the case of CH(4)-C(3)H(8) hydrates, a conversion in the presence of gaseous CO(2) from a supposedly more stable structure II hydrate to a less stable structure I CO(2)-rich hydrate was observed. PXRD data show that the reverse process requires longer initiation times, and structural changes seem to be less complete. Generally, the exchange process can be described as a decomposition and reformation process, in terms of a rearrangement of molecules, and is primarily induced by the chemical potential gradient between hydrate phase and the provided gas phase. The results show furthermore the dependency of the conversion rate on the surface area of the hydrate phase, the thermodynamic stability of the original and resulting hydrate phase, as well as the mobility of guest molecules and formation kinetics of the resulting hydrate phase.

Review of Chemical, Biological, Radiological, and Nuclear (CBRN) Terminology in Technical Guide 316 (TG 316) and Allied Medical Publication 8(C) (AMedP-8(C))

DTIC Science & Technology

2013-05-01

tularensis causing pneumonic tularemia (Aberdeen Proving Ground, MD: USAPHC, January 2012); USAPHC, Technical Guide 316 Supplement F1; USAPHC, Technical...Phase I preliminary BMEGs are completed for anthrax, plague, tularemia , ricin, and Staphylococcal Enterotoxin B (SEB). The Phase II process has been...Exposure to Specified Biological Agents: Brucellosis, Glanders, Q Fever, SEB and Tularemia , IDA Document D-4132 (Alexandria, VA: Institute for Defense

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

Randomized Phase II Trial of Adjuvant WT -1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2016-09-01

Interest Group 2016 Meeting Poster discussion at the American Society of Clinical Oncology Annual Meeting 2016 CONCLUSION: The clinical trial is now...Clinical Oncology 2016 Annual Meeting, Chicago, IL, Poster Discussion Presentation, June 4, 2016. APPENDICES: None SUPPORTING DATA: None

Venetoclax Yields Strong Responses in CLL.

PubMed

2016-02-01

Results from an international phase II study show that the investigational BCL2 inhibitor venetoclax is effective in patients with chronic lymphocytic leukemia and the chromosome 17p deletion, whose prognosis is particularly poor. Venetoclax yielded high and durable responses in this population, including several complete remissions. ©2016 American Association for Cancer Research.

17 CFR 242.608 - Filing and amendment of national market system plans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... national market subsystem or facility contemplated by a national market system plan; (ii) Preparing and... date of completion of each phase; (C) An analysis of the impact on competition of implementation of the..., operation, or regulation of a national market system (or a subsystem thereof) or one or more facilities...

17 CFR 242.608 - Filing and amendment of national market system plans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... national market subsystem or facility contemplated by a national market system plan; (ii) Preparing and... date of completion of each phase; (C) An analysis of the impact on competition of implementation of the..., operation, or regulation of a national market system (or a subsystem thereof) or one or more facilities...

17 CFR 242.608 - Filing and amendment of national market system plans.

Code of Federal Regulations, 2013 CFR

2013-04-01

... national market subsystem or facility contemplated by a national market system plan; (ii) Preparing and... date of completion of each phase; (C) An analysis of the impact on competition of implementation of the..., operation, or regulation of a national market system (or a subsystem thereof) or one or more facilities...

17 CFR 242.608 - Filing and amendment of national market system plans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... national market subsystem or facility contemplated by a national market system plan; (ii) Preparing and... date of completion of each phase; (C) An analysis of the impact on competition of implementation of the..., operation, or regulation of a national market system (or a subsystem thereof) or one or more facilities...

17 CFR 242.608 - Filing and amendment of national market system plans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... national market subsystem or facility contemplated by a national market system plan; (ii) Preparing and... date of completion of each phase; (C) An analysis of the impact on competition of implementation of the..., operation, or regulation of a national market system (or a subsystem thereof) or one or more facilities...

Results of the phase II study of photodynamic therapy in Japan

NASA Astrophysics Data System (ADS)

Konaka, Chimori; Kato, Harubumi; Okunaka, Tetsuya; Hayata, Yoshihiro

1994-07-01

Photodynamic therapy (PDT) utilizing Photofrin has proven to be an effective modality used in the treatment of solid tumors. In particular, it can be applied via endoscopy to lesions developing in luminal organs. A phase II study was conducted for submission to the Japanese Ministry of Health and Welfare. In this protocol an excimer dye laser was used to deliver 630 nm light via a quartz fiber passed through an endoscopic working channel two days subsequent to i.v. injection of photosensitizer. In this study, 98 patients with superficial cancer of various organs were treated. Of these, 88 patients could be evaluated, including 33 with roentgenographically occult lung cancer, 10 with esophageal cancer, 24 with gastric cancer, 18 with cervical cancer and three with bladder cancer. Complete remission as evaluated endoscopically, pathologically, and cytologically was obtained in 83 out of 98 (84.7). There was no serious complication except mild skin photosensitivity, which was seen in four patients. It was concluded that PDT can be efficacious in the treatment of superficial cancers and that complete remission can be achieved when suitable photoradiation conditions are met.

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study.

PubMed

Torresi, Joseph; Heron, Leon G; Qiao, Ming; Marjason, Joanne; Chambonneau, Laurent; Bouckenooghe, Alain; Boaz, Mark; van der Vliet, Diane; Wallace, Derek; Hutagalung, Yanee; Nissen, Michael D; Richmond, Peter C

2015-09-22

The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Design specifications for NALDA (Naval Aviation Logistics Data Analysis) CAI (computer aided instruction): Phase 2, Interim report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twitty, A.F.; Handler, B.H.; Duncan, L.D.

Data Systems Engineering Organization (DSEO) personnel are developing a prototype computer aided instruction (CAI) system for the Naval Aviation Logistics Data Analysis (NALDA) system. The objective of this project is to provide a prototype for implementing CAI as an enhancement to existing NALDA training. The CAI prototype project is being performed in phases. The task undertaken in Phase I was to analyze the problem and the alternative solutions and to develop a set of recommendations on how best to proceed. In Phase II a structured design and specification document was completed that will provide the basis for development and implementationmore » of the desired CAI system. Phase III will consist of designing, developing, and testing a user interface which will extend the features of the Phase II prototype. The design of the CAI prototype has followed a rigorous structured analysis based on Yourdon/DeMarco methodology and Information Engineering tools. This document includes data flow diagrams, a data dictionary, process specifications, an entity-relationship diagram, a curriculum description, special function key definitions, and a set of standards developed for the NALDA CAI Prototype.« less

Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2017-11-01

journal of cancer research : Gann 1999; 90(2): 194-204. 6. Rosenfeld C, Cheever MA, Gaiger A. WT1 in acute leukemia, chronic myelogenous leukemia...and myelodysplastic syndrome : therapeutic potential of WT1 targeted therapies. Leukemia 2003; 17(7): 1301-12. 7. Cheever MA, Allison JP, Ferris AS...Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid

Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

PubMed

Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2016-10-01

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Determination of model parameters for zinc (II) ion biosorption onto powdered waste sludge (PWS) in a fed-batch system.

PubMed

Kargi, Fikret; Cikla, Sinem

2007-12-01

Biosorption of zinc (II) ions onto pre-treated powdered waste sludge (PWS) was investigated using a completely mixed tank operating in fed-batch mode instead of an adsorption column. Experiments with variable feed flow rate (0.05-0.5 L h(-1)), feed Zn(II) ion concentrations (37.5-275 mg L(-1)) and amount of adsorbent (1-6 g PWS) were performed using fed-batch operation at pH 5 and room temperature (20-25 degrees C). Break-through curves describing variations of aqueous (effluent) zinc ion concentrations with time were determined for different operating conditions. Percent zinc removal from the aqueous phase decreased, but the biosorbed (solid phase) zinc ion concentration increased with increasing feed flow rate and zinc concentration. A modified Bohart-Adams equation was used to determine the biosorption capacity of PWS (q'(s)) and the rate constant (K) for zinc ion biosorption. Biosorption capacity (q'(s)=57.7 g Zn kg(-1) PWS) of PWS in fed-batch operation was found to be comparable with powdered activated carbon (PAC) in column operations. However, the adsorption rate constant (K=9.17 m(3) kg(-1) h(-1)) in fed-batch operation was an order of magnitude larger than those obtained in adsorption columns because of elimination of mass transfer limitations encountered in the column operations. Therefore, a completely mixed tank operated in fed-batch mode was proven to be more advantageous as compared to adsorption columns due to better contact between the phases yielding faster adsorption rates.

Effect of patient-centered communication training on discussion and detection of nonadherence in glaucoma.

PubMed

Hahn, Steven R; Friedman, David S; Quigley, Harry A; Kotak, Sameer; Kim, Elizabeth; Onofrey, Meaghan; Eagan, Corey; Mardekian, Jack

2010-07-01

To assess communication about adherence and to determine the impact of communication skills training on physicians' approach to nonadherence. Sociolinguistic analysis of videotaped community ophthalmologists' encounters with patients with glaucoma before and after training. Patients in both phases and physicians in phase I knew communication was being studied but not what the focus of the study was. In phase II, physicians knew the targeted communication behaviors. Twenty-three ophthalmologists and 100 regularly scheduled patients with glaucoma (50 per phase). An educational program with videotaped vignettes of simulated patient encounters using audience response and role play to teach patient-centered communication skills, including a 4-step adherence assessment and the use of open-ended questions in ask-tell-ask sequences. Physician eliciting an acknowledgment of nonadherence during a clinical encounter compared with acknowledgment of nonadherence during a postvisit research interview (primary outcome), and performance of targeted communication and substantive discussion of adherence. After intervention, physicians increased the proportion of open-ended questions (15% vs 6%; P = 0.001) and specifically about medication taking (82% compared with 18% of encounters; P<0.001). Compared with the absence of ask-tell-ask communication, 32% of phase II encounters included a complete ask-tell-ask sequence, 78% included an ask-tell sequence, and 32% a tell-ask sequence (P<0.001). Three of 4 steps for assessment of adherence were more common in phase II, and substantial discussions of adherence occurred in 86% versus 30% of encounters (P<0.001). In phase II, physicians elicited acknowledgment of nonadherence in 78% (7/9) of those who acknowledged nonadherence in the postvisit interview compared with 25% in phase I (3/12; P = 0.03). This study demonstrates that experienced community physicians significantly improved their communication strategies and ability to detect and address nonadherence after a 3-hour educational program. Proprietary or commercial disclosure may be found after the references. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.

PubMed

Mills, Edward; Wilson, Kumanan; Clarke, Mike; Foster, Brian; Walker, Scott; Rachlis, Beth; DeGroot, Nick; Montori, Victor M; Gold, Wayne; Phillips, Elizabeth; Myers, Stephen; Gallicano, Keith

2005-03-01

To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.

Experiences of Work-Life Conflict for the Athletic Trainer Employed Outside the National Collegiate Athletic Association Division I Clinical Setting.

PubMed

Mazerolle, Stephanie M; Pitney, William A; Eason, Christianne M

2015-07-01

The intercollegiate setting receives much of the scholarly attention related to work-life conflict (WLC). However research has been focused on the National Collegiate Athletic Association Division I setting. Multiple factors can lead to WLC for the athletic trainer (AT), including hours, travel, and lack of flexibility in work schedules. To investigate the experiences of WLC among ATs working in the non-Division I collegiate setting and to identify factors that contribute to fulfillment of work-life balance in this setting. Qualitative study. Institutions in the National Collegiate Athletic Association Divisions II and III, the National Association of Intercollegiate Athletics, and the National Junior College Athletic Association. A total of 244 ATs (128 women, 114 men; age = 37.5 ± 13.3 years, experience = 14 ± 12 years) completed phase I. Thirteen participants (8 women, 5 men; age = 38 ± 13 years, experience = 13.1 ± 11.4 years) completed phase II. For phase I, participants completed a previously validated and reliable (Cronbach α > .90) Web-based survey measuring their levels of WLC and work-family conflict (WFC). This phase included 2 WFC scales defining family; scale 1 defined family as having a partner or spouse with or without children, and scale 2 defined family as those individuals, including parents, siblings, grandparents, and any other close relatives, involved in one's life. Phase II consisted of an interview. Qualitative data were evaluated using content analysis. Data source and multiple-analyst triangulation secured credibility. The WFC scores were 26.33 ± 7.37 for scale 1 and 20.46 ± 10.14 for scale 2, indicating a moderate level of WFC for scale 1 and a low level of WFC for scale 2. Qualitative analyses revealed that organizational dimensions, such as job demands and staffing issues, can negatively affect WLC, whereas a combination of organizational and personal dimensions can positively affect WLC. Overload continues to be a prevalent factor in negatively influencing WLC and WFC. Supervisor and peer support, personal networks, and time away from the role positively influenced work-life balance and WFC. Athletic trainers are encouraged to support one another in the workplace, especially when providing flexibility in scheduling.

Experiences of Work-Life Conflict for the Athletic Trainer Employed Outside the National Collegiate Athletic Association Division I Clinical Setting

PubMed Central

Mazerolle, Stephanie M.; Pitney, William A.; Eason, Christianne M.

2015-01-01

Context The intercollegiate setting receives much of the scholarly attention related to work-life conflict (WLC). However research has been focused on the National Collegiate Athletic Association Division I setting. Multiple factors can lead to WLC for the athletic trainer (AT), including hours, travel, and lack of flexibility in work schedules. Objective To investigate the experiences of WLC among ATs working in the non-Division I collegiate setting and to identify factors that contribute to fulfillment of work-life balance in this setting. Design Qualitative study. Setting Institutions in the National Collegiate Athletic Association Divisions II and III, the National Association of Intercollegiate Athletics, and the National Junior College Athletic Association. Patients or Other Participants A total of 244 ATs (128 women, 114 men; age = 37.5 ± 13.3 years, experience = 14 ± 12 years) completed phase I. Thirteen participants (8 women, 5 men; age = 38 ± 13 years, experience = 13.1 ± 11.4 years) completed phase II. Data Collection and Analysis For phase I, participants completed a previously validated and reliable (Cronbach α > .90) Web-based survey measuring their levels of WLC and work-family conflict (WFC). This phase included 2 WFC scales defining family; scale 1 defined family as having a partner or spouse with or without children, and scale 2 defined family as those individuals, including parents, siblings, grandparents, and any other close relatives, involved in one's life. Phase II consisted of an interview. Qualitative data were evaluated using content analysis. Data source and multiple-analyst triangulation secured credibility. Results The WFC scores were 26.33 ± 7.37 for scale 1 and 20.46 ± 10.14 for scale 2, indicating a moderate level of WFC for scale 1 and a low level of WFC for scale 2. Qualitative analyses revealed that organizational dimensions, such as job demands and staffing issues, can negatively affect WLC, whereas a combination of organizational and personal dimensions can positively affect WLC. Conclusions Overload continues to be a prevalent factor in negatively influencing WLC and WFC. Supervisor and peer support, personal networks, and time away from the role positively influenced work-life balance and WFC. Athletic trainers are encouraged to support one another in the workplace, especially when providing flexibility in scheduling. PMID:25879575

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

Translating and testing the ENABLE: CHF-PC concurrent palliative care model for older adults with heart failure and their family caregivers.

PubMed

Dionne-Odom, J Nicholas; Kono, Alan; Frost, Jennifer; Jackson, Lisa; Ellis, Daphne; Ahmed, Ali; Azuero, Andres; Bakitas, Marie

2014-09-01

Heart failure (HF) and palliative care (PC) organizations recommend early PC to improve the quality of life of patients living with HF. We conducted a two-phase formative evaluation study to translate a cancer-focused concurrent PC intervention into one that would be appropriate for rural-dwelling adults with New York Heart Association Class III-IV HF and their primary caregivers. Phase I: We tailored the intervention for an HF population via literature review, expert consultation, and clinician (N=15) small group interviews. Phase II: We enrolled 11 patient/caregiver dyads to assess intervention feasibility and satisfaction. We assessed participants' experiences and satisfaction after session/week three and session/week six via digitally recorded interviews. Clinician and participant interviews were transcribed and content analyzed. Outcome measures were evaluated for completion rates and effect sizes. Phase I: Clinicians described barriers to initiating PC in HF, triggers for initiating PC, and suggestions for intervention improvement. Phase II: Participants were able to complete the majority of study sessions, measures, and interviews. Satisfaction interviews revealed the content to be relevant and comprehensive in addressing HF patient and caregiver primary concerns; however, participants unanimously suggested making the intervention available earlier in the illness trajectory. Efficacy measures demonstrated small to medium effect sizes. We tailored and demonstrated feasibility of providing an early, concurrent palliative care intervention to patients with advanced HF and their caregivers. Based on this experience we are now conducting an efficacy trial in a racially diverse sample.

Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.

PubMed

Abe, Masakazu; Hirashima, Yasuyuki; Kasamatsu, Yuka; Kado, Nobuhiro; Komeda, Satomi; Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Takekuma, Munetaka; Hihara, Hanako; Ichikawa, Yoshikazu; Itonaga, Yui; Hirakawa, Tomoko; Nasu, Kaei; Miyagi, Kanoko; Murakami, Junko; Ito, Kimihiko

2016-02-01

Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Exploration of how women make treatment decisions after a breast cancer diagnosis.

PubMed

Spittler, Cheryl A; Pallikathayil, Leonie; Bott, Marjorie

2012-09-01

To examine the information needs of women after receiving a diagnosis of breast cancer, investigate how decisions about treatment options are made, and assess personal responses to the decisions made. Mixed-methods approach using quantitative and qualitative data. The University of Kansas Medical Center and Quinn Plastic Surgery Center, both in the midwestern United States. 102 breast cancer survivors who had completed all forms of treatment for at least three months and less than five years. Phase I participants completed five questionnaires about informational needs, confidence and satisfaction with the decision, decisional regret, and conflict. In phase II, 15 participants were purposively sampled from the 102 survivors to participate in a focus group session. Data analysis included frequencies and multiple regression for phase I and qualitative content analysis for phase II. Informational needs, confidence and satisfaction with the decision, and decisional regret and conflict. The variables (widowed, confidence and satisfaction with decision, and decisional conflict and regret) significantly (p = 0.01) accounted for 14% of the variance in informational needs. Two themes emerged from the study: (a) feelings, thoughts, and essential factors that impact treatment considerations, and (b) tips for enhancing treatment consideration options. The study's results show that women viewed informational needs as very important in making treatment decisions after being diagnosed with breast cancer. The treatment team should provide the information, with consideration of the patient's personal preferences, that will assist women to make informed, confident, and satisfied decisions about treatment choices.

Bayesian adaptive phase II screening design for combination trials.

PubMed

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial.

Investigational Drugs for Visceral Leishmaniasis

PubMed Central

Sundar, Shyam; Chakravarty, Jaya

2014-01-01

Introduction The armamentarium of antileishmanials is small. It is further being threatened by development of resistance and decreasing sensitivity to the available drugs. Development of newer drugs are sorely needed. Areas covered Literature search on investigational drugs for visceral leishmaniasis (VL) was done on PubMed. Those candidates with at least in vitro and in vivo activity against leishmania species causing VL were reviewed. Among the investigational drugs the nitroimidazole compound fexinidazole is the one of the few drugs which has reached phase II trials. Although the (S)-PA-824 is in phase II trials for the treatment of tuberculosis its R enantiomer has shown good antileishmanial activity. Development of sitamaquin, which has completed phase II studies has been stopped for VL due to its low efficacy. Many novel delivery system and oral formulations of Amphotericin B which are cheap and less toxic are in investigational stages, and will go a long way in improving the treatment of VL. Expert opinion Very few new drugs have reached the clinical stage in the treatment of this neglected tropical disease. Thus, there is an urgent need for support from public private partnerships to ensure that drug candidates are promptly taken forward into development. PMID:25409760

Phase II drugs currently being investigated for the treatment of hypogonadism.

PubMed

Udedibia, Emeka; Kaminetsky, Jed

2014-12-01

Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway.

PubMed

Morimitsu, Yasujiro; Nakagawa, Yoko; Hayashi, Kazuhiro; Fujii, Hiroyuki; Kumagai, Takeshi; Nakamura, Yoshimasa; Osawa, Toshihiko; Horio, Fumihiko; Itoh, Ken; Iida, Katsuyuki; Yamamoto, Masayuki; Uchida, Koji

2002-02-01

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of the protective phase II detoxification enzymes, such as glutathione S-transferase (GST). We have recently developed a cell culture system, using rat liver epithelial RL 34 cells, that potently responds to the phenolic antioxidants resulting in the induction of GST activity (Kawamoto, Y., Nakamura, Y., Naito, Y., Torii, Y., Kumagai, T., Osawa, T., Ohigashi, H., Satoh, K., Imagawa, M., and Uchida, K. (2000) J. Biol. Chem. 275, 11291-11299.) In the present study, we investigated the phase II-inducing potency of an isothiocyanate compound in vitro and in vivo and examined a possible induction mechanism. Based on an extensive screening of vegetable extracts for GST inducer activity in RL34 cells, we found Japanese horseradish, wasabi (Wasabia japonica, syn. Eutrema wasabi), as the richest source and identified 6-methylsulfinylhexyl isothiocyanate (6-HITC), an analogue of sulforaphane (4-methylsulfinylbutyl isothiocyanate) isolated from broccoli, as the major GST inducer in wasabi. 6-HITC potently induced both class alpha GSTA1 and class pi GSTP1 isozymes in RL34 cells. In animal experiments, we found that 6-MSHI was rapidly absorbed into the body and induced hepatic phase II detoxification enzymes more potently than sulforaphane. The observations that (i) 6-HITC activated the antioxidant response element (ARE), (ii) 6-HITC induced nuclear localization of the transcription factor Nrf2 that binds to ARE, and (iii) the induction of phase II enzyme genes by 6-HITC was completely abrogated in the nrf2-deficient mice, suggest that 6-HITC is a potential activator of the Nrf2/ARE-dependent detoxification pathway.

An audit of growth hormone replacement for GH-deficient adults in Scotland.

PubMed

Philip, Sam; Howat, Isobel; Carson, Maggie; Booth, Anne; Campbell, Karen; Grant, Donna; Patterson, Catherine; Schofield, Christopher; Bevan, John; Patrick, Alan; Leese, Graham; Connell, John

2013-04-01

Guidelines on the clinical use of growth hormone therapy in adults were issued by the UK National Institute for Clinical Excellence (NICE) in August 2003. We conducted a retrospective clinical audit on the use of growth hormone (GH) in Scotland to evaluate the use of these guidelines and their impact on clinical practice. The audit had two phases. In phase I, the impact of NICE criteria on specialist endocrine practice in starting and continuing GH replacement was assessed. In phase II, the reasons why some adults in Scotland with growth hormone deficiency were not on replacement therapy were evaluated. A retrospective cross-sectional case note review was carried out of all adult patients being followed up for growth hormone deficiency during the study period (1 March 2005 to 31 March 2008). Phase I of the audit included 208 patients and phase II 108 patients. Sellar tumours were the main cause of GH deficiency in both phases of the audit. In phase I, 53 patients (77%) had an AGHDA-QoL score >11 documented before commencing GH post-NICE guidance, compared with 35 (25%) pre-NICE guidance. Overall, only 39 patients (18%) met the full NICE criteria for starting and continuing GH (pre-NICE, 11%; post-NICE, 35%). Phase II indicated that the main reasons for not starting GH included perceived satisfactory quality of life (n = 47, 43%), patient reluctance (16, 15%) or a medical contraindication (16, 15%). Although the use of quality of life assessments has increased following publication of the NICE guidelines, most adults on GH in Scotland did not fulfil the complete set of NICE criteria. The main reason for not starting GH therapy in adult GH-deficient patients was perceived satisfactory quality of life. © 2012 Blackwell Publishing Ltd.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PubMed Central

Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

2012-01-01

Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. PMID:22915658

High-speed, multi-channel detector readout electronics for fast radiation detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hennig, Wolfgang

2012-06-22

In this project, we are developing a high speed digital spectrometer that a) captures detector waveforms at rates up to 500 MSPS b) has upgraded event data acquisition with additional data buffers for zero dead time operation c) moves energy calculations to the FPGA to increase spectrometer throughput in fast scintillator applications d) uses a streamlined architecture and high speed data interface for even faster readout to the host PC These features are in addition to the standard functions in our existing spectrometers such as digitization, programmable trigger and energy filters, pileup inspection, data acquisition with energy and time stamps,more » MCA histograms, and run statistics. In Phase I, we upgraded one of our existing spectrometer designs to demonstrate the key principle of fast waveform capture using a 500 MSPS, 12 bit ADC and a Xilinx Virtex-4 FPGA. This upgraded spectrometer, named P500, performed well in initial tests of energy resolution, pulse shape analysis, and timing measurements, thus achieving item (a) above. In Phase II, we are revising the P500 to build a commercial prototype with the improvements listed in items (b)-(d). As described in the previous report, two devices were built to pursue this goal, named the Pixie-500 and the Pixie-500 Express. The Pixie-500 has only minor improvements from the Phase I prototype and is intended as an early commercial product (its production and part of its development were funded outside the SBIR). It also allows testing of the ADC performance in real applications.The Pixie-500 Express (or Pixie-500e) includes all of the improvements (b)-(d). At the end of Phase II of the project, we have tested and debugged the hardware, firmware and software of the Pixie-500 Express prototype boards delivered 12/3/2010. This proved substantially more complex than anticipated. At the time of writing, all hardware bugs have been fixed, the PCI Express interface is working, the SDRAM has been successfully tested and the SHARC DSP has been booted with preliminary code. All new ICs and circuitry on the prototype are working properly, however some of the planned firmware and software functions have not yet been completely implemented and debugged. Overall, due to the unanticipated complexity of the PCI Express interface, some aspects of the project could not be completed with the time and funds available in Phase II. These aspects will be completed in self-funded Phase III.« less

Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

PubMed

Wang, Ling-Wei; Hsiao, Chin-Fu; Chen, William Tzu-Liang; Lee, Hao-Hsien; Lin, Tzu-Chen; Chen, Hung-Chang; Chen, Hong-Hwa; Chien, Chun-Ru; Lin, Tze-Yi; Liu, Tsang-Wu

2014-05-01

To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery. © 2013 Wiley Periodicals, Inc.

1-(2-Formamidoethyl)-3-phenylurea functionalized activated carbon for selective solid-phase extraction and preconcentration of metal ions.

PubMed

Tu, Zhifeng; He, Qun; Chang, Xijun; Hu, Zheng; Gao, Ru; Zhang, Lina; Li, Zhenhua

2009-09-07

A novel method that utilizes 1-(2-formamidoethyl)-3-phenylurea-modified activated carbon (AC-1-(2-formamidoethyl)-3-phenylurea) as a solid-phase extractant has been developed for simultaneous preconcentration of trace Cr(III), Cu(II), Fe(III) and Pb(II) prior to the measurement by inductively coupled plasma atomic emission spectrometry (ICP-AES). Experimental conditions for effective adsorption of trace levels of Cr(III), Cu(II), Fe(III) and Pb(II) were optimized using batch and column procedures in detail. The optimum pH value for the separation of metal ions simultaneously on the new sorbent was 4. And the adsorbed metal ions could be completely eluted by using 2.0 mL 2.0 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation and determination of target metal ions. The maximum static adsorption capacity of the sorbent at optimum conditions was found to be 39.8, 39.9, 77.8 and 17.3 mg g(-1) for Cr(III), Cu(II), Fe(III) and Pb(II), respectively. The detection limits of the method were found to be 0.15, 0.41, 0.27 and 0.36 ng mL(-1) for Cr(III), Cu(II), Fe(III) and Pb(II), respectively. The relative standard deviation (RSD) of the method was lower than 4.0% (n=8). The method was successfully applied for the preconcentration of trace Cr(III), Cu(II), Fe(III) and Pb(II) in natural and certified samples with satisfactory results.

Intermittent Versus Daily Pulmonary Tuberculosis Treatment Regimens: A Meta-Analysis

PubMed Central

Kasozi, Samuel; Clark, Justin; Doi, Suhail A. R.

2015-01-01

Background Several systematic reviews suggest that intermittent pulmonary tuberculosis (TB) chemotherapy is effective, but intensity (daily versus intermittent) and duration of rifampicin use (intensive phase only versus both phases) have not been distinguished. In addition, the various outcomes (success, failure, relapse, and default) have only selectively been evaluated. Methods We conducted a meta-analysis of proportions using all four outcomes as multi-category proportions to examine the effectiveness of WHO category 1 TB treatment regimens. Database searches of studies reporting treatment outcomes of HIV negative subjects were included and stratified by intensity of therapy and duration of rifampicin therapy. Using a bias-adjusted statistical model, we pooled proportions of the four treatment outcome categories using a method that handles multi-category proportions. Results A total of 27 studies comprising of 48 data sets with 10,624 participants were studied. Overall, treatment success was similar among patients treated with intermittent (I/I) (88%) (95% CI, 81–92) and daily (D/D) (90%) (95% CI, 84–95) regimens. Default was significantly less with I/I (0%) (95% CI, 0–2) compared to D/D regimens (5%) (95% CI, 1–9). Nevertheless, I/I relapse rates (7%) (95% CI, 3–11) were higher than D/D relapse rates (1%) (95% CI, 0–3). Conclusion Treatment regimens that are offered completely intermittently versus completely daily are associated with a trade-off between treatment relapse and treatment default. There is a possibility that I/I regimens can be improved by increasing treatment duration, and this needs to be urgently addressed by future studies. PMID:26056374

Small Business Innovation Research GRC Phase I, Phase II, and Post-Phase II Opportunity Assessment for 2015

NASA Technical Reports Server (NTRS)

Nguyen, Hung D.; Steele, Gynelle C.

2016-01-01

This report outlines the 2015 Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) Phase I, Phase II, and Post-Phase II opportunity contract award results associated with NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD) for NASA Glenn Research Center. The report also highlights the number of Phase I, Phase II, and Post-Phase II contracts awarded by mission directorate. The 2015 Phase I contract awards to companies in Ohio and their corresponding technologies are also discussed.

Human Data Supporting Glyburide in Ischemic Stroke

PubMed Central

Sheth, Kevin N.; Simard, J. Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W. Taylor

2016-01-01

The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous (IV) formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. Early phase II study of MRI and plasma biomarkers support the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase IIb study and definitive efficacy studies are urgently needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

PubMed

Noordman, Bo Jan; Wijnhoven, Bas P L; Lagarde, Sjoerd M; Boonstra, Jurjen J; Coene, Peter Paul L O; Dekker, Jan Willem T; Doukas, Michael; van der Gaast, Ate; Heisterkamp, Joos; Kouwenhoven, Ewout A; Nieuwenhuijzen, Grard A P; Pierie, Jean-Pierre E N; Rosman, Camiel; van Sandick, Johanna W; van der Sangen, Maurice J C; Sosef, Meindert N; Spaander, Manon C W; Valkema, Roelf; van der Zaag, Edwin S; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-02-06

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

Improved Tubulars for Better Economics in Deep Gas Well Drilling Using Microwave Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinesh Agrawal

2006-09-30

The main objective of the entire research program has been to improve the rate-of-penetration in deep hostile environments by improving the life cycle and performance of coiled-tubing, an important component of a deep well drilling system for oil and gas exploration, by utilizing the latest developments in the microwave materials technology. Based on the results of the Phase I and insurmountable difficulties faced in the extrusion and de-waxing processes, the approach of achieving the goals of the program was slightly changed in the Phase II in which an approach of microwave sintering combined with Cold Isostatic Press (CIP) and joiningmore » (by induction or microwave) has been adopted. This process can be developed into a semicontinuous sintering process if the CIP can produce parts fast enough to match the microwave sintering rates. The main objective of the Phase II research program is to demonstrate the potential to economically manufacture microwave processed coiled tubing with improved performance for extended useful life under hostile coiled tubing drilling conditions. After the completion of the Phase II, it is concluded that scale up and sintering of a thin wall common O.D. size tubing that is widely used in the market is still to be proved and further experimentation and refinement of the sintering process is needed in Phase III. Actual manufacturing capability of microwave sintered, industrial quality, full length tubing will most likely require several million dollars of investment.« less

Improved Tubulars for Better Economics in Deep Gas Well Drilling using Microwave Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinesh Agrawal; Paul Gigl; Mark Hunt

2007-07-31

The main objective of the entire research program has been to improve the rate-of-penetration in deep hostile environments by improving the life cycle and performance of coiled-tubing, an important component of a deep well drilling system for oil and gas exploration, by utilizing the latest developments in the microwave materials technology. Based on the results of the Phase I and insurmountable difficulties faced in the extrusion and de-waxing processes, the approach of achieving the goals of the program was slightly changed in the Phase II in which an approach of microwave sintering combined with Cold Isostatic Press (CIP) and joiningmore » (by induction or microwave) has been adopted. This process can be developed into a semicontinuous sintering process if the CIP can produce parts fast enough to match the microwave sintering rates. The main objective of the Phase II research program is to demonstrate the potential to economically manufacture microwave processed coiled tubing with improved performance for extended useful life under hostile coiled tubing drilling conditions. After the completion of the Phase II, it is concluded that scale up and sintering of a thin wall common O.D. size tubing that is widely used in the market is still to be proved and further experimentation and refinement of the sintering process is needed in Phase III. Actual manufacturing capability of microwave sintered, industrial quality, full length tubing will most likely require several million dollars of investment.« less

CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia.

PubMed

Cramer, Paula; von Tresckow, Julia; Bahlo, Jasmin; Engelke, Anja; Langerbeins, Petra; Fink, Anna-Maria; Fischer, Kirsten; Wendtner, Clemens-Martin; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

2018-03-01

Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity. This strategy represents a new era of chronic lymphocytic leukemia therapy where chemotherapy is increasingly replaced by targeted agents and treatment duration is tailored to the patient's individual tumor load and response.

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide versus gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group Study JCOG1306.

PubMed

Kataoka, Kozo; Tanaka, Kazuhiro; Mizusawa, Junki; Kimura, Aya; Hiraga, Hiroaki; Kawai, Akira; Matsunobu, Tomoya; Matsumine, Akihiko; Araki, Nobuhito; Oda, Yoshinao; Fukuda, Haruhiko; Iwamoto, Yukihide

2014-08-01

A randomized Phase II/III trial was planned to commence in March 2014. Perioperative chemotherapy with adriamycin plus ifosfamide is the current standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The purpose of this study is to confirm the non-inferiority of perioperative chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the extremities and body wall. A total of 140 patients will be accrued from 28 Japanese institutions over 6 years. The primary endpoint in the Phase II part is the proportion of completion of pre-operative chemotherapy without progressive disease and overall survival in the Phase III part. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, pathological response rate, proportion of preservation of diseased limbs, disease control rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000013175 [http://www.umin.ac.jp/ctr/index.htm]. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An Overview of the Cooperative Effort between the United States Department of Energy and the China Atomic Energy Authority to Enhance MPC&A Inspections for Civil Nuclear Facilities in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahern, Keith; Daming, Liu; Hanley, Tim

The United States Department of Energy, National Nuclear Security Administration (DOE/NNSA) and the China Atomic Energy Authority (CAEA) are cooperating to enhance the domestic regulatory inspections capacity for special nuclear material protection, control and accounting (MPC&A) requirements for civil nuclear facilities in China. This cooperation is conducted under the auspices of the Agreement between the Department of Energy of the United States of America and the State Development and Planning Commission of the People s Republic of China on Cooperation Concerning Peaceful Uses of Nuclear Technology. This initial successful effort was conducted in three phases. Phase I focused on introducingmore » CAEA personnel to DOE and U. S. Nuclear Regulatory Commission inspection methods for U. S. facilities. This phase was completed in January 2008 during meetings in Beijing. Phase II focused on developing physical protection and material control and accounting inspection exercises that enforced U. S. inspection methods identified during Phase 1. Hands on inspection activities were conducted in the United States over a two week period in July 2009. Simulated deficiencies were integrated into the inspection exercises. The U. S. and Chinese participants actively identified and discussed deficiencies noted during the two week training course. The material control and accounting inspection exercises were conducted at the Paducah Gaseous Diffusion Plant (PGDP) in Paducah, KY. The physical protection inspection exercises were conducted at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, TN. Phase III leveraged information provided under Phase I and experience gained under Phase II to develop a formal inspection guide that incorporates a systematic approach to training for Chinese MPC&A field inspectors. Additional hands on exercises that are applicable to Chinese regulations were incorporated into the Phase III training material. Phase III was completed in May 2010 at the China Institute of Atomic Energy (CIAE) in Beijing. This paper provides details of the successful cooperation between DOE/NNSA and CAEA for all phases of the cooperative effort to enhance civil domestic MPC&A inspections in China.« less

Characteristics associated with Sleep Duration, Chronotype, and Social jet lag in Adolescents

PubMed Central

Malone, Susan Kohl; Zemel, Babette S.; Compher, Charlene; Souders, Margaret; Chittams, Jesse; Thompson, Aleda Leis; Lipman, Terri H.

2015-01-01

Sleep is a complex behavior with numerous health implications. Identifying socio-demographic and behavioral characteristics of sleep are important for determining those at greatest risk for sleep-related health disparities. In this cross-sectional study, general linear models were used to examine socio-demographic and behavioral characteristics associated with sleep duration, chronotype, and social jet lag in adolescents. One hundred fifteen participants completed Phase I (self-reported sleep measures); 69 of these participants completed Phase II (actigraphy-estimated sleep measures). Black adolescents had shorter free night sleep than Hispanics. Youth with later chronotypes ate fewer fruits and vegetables, drank more soda, were less physically active, and took more daytime naps. Based on these findings, recommendations for individual support and school policies are provided. PMID:26376832

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

PubMed

Chawla, Sant P; Cranmer, Lee D; Van Tine, Brian A; Reed, Damon R; Okuno, Scott H; Butrynski, James E; Adkins, Douglas R; Hendifar, Andrew E; Kroll, Stew; Ganjoo, Kristen N

2014-10-10

TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). © 2014 by American Society of Clinical Oncology.

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

PubMed

Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. ClinicalTrials.gov NCT01136161.

Technology evaluation: VEGF165 gene therapy, Valentis Inc.

PubMed

Morse, M A

2001-02-01

Valentis Inc, formerly GeneMedicine, is developing a vascular endothelial growth factor (VEGF165) non-viral gene therapy using its proprietary PINC polymer for plasmid condensation. Two physician-initiated phase II angioplasty trials are ongoing, one for treating peripheral vascular disease and one for treating coronary artery disease [281714], [347153]. In February 2000, the trials were expected to be completed in the fourth quarter of 2000 [356225]; however, in October 2000, it was reported that the trial for peripheral vascular disease would be completed in the first quarter of 2001 [385232]. In March 2000, Valentis initiated a trial incorporating Valentis's DOTMA-based cationic lipid gene delivery system and the VEGF165 gene with Eurogene's local collar-reservoir delivery device. The trial is designed to demonstrate that the VEGF165 gene, delivered locally to the outside surface of a blood vessel, will transfect and express in the smooth muscle cells of the vessel wall [360683]. In March 1999, Valentis was awarded with a Phase II SBIR grant of $686,260. The aim of grant was to advance the development of non-viral gene therapies for ischemia. Specifically, Valentis intended to select an optimal promoter to be used with the VEGF expression plasmid. Valentis also intended to evaluate the gene therapy system in a rabbit ischemia model and complete the necessary preclinical studies for submission of an IND [318137].

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Quantum phase space with a basis of Wannier functions

NASA Astrophysics Data System (ADS)

Fang, Yuan; Wu, Fan; Wu, Biao

2018-02-01

A quantum phase space with Wannier basis is constructed: (i) classical phase space is divided into Planck cells; (ii) a complete set of Wannier functions are constructed with the combination of Kohn’s method and Löwdin method such that each Wannier function is localized at a Planck cell. With these Wannier functions one can map a wave function unitarily onto phase space. Various examples are used to illustrate our method and compare it to Wigner function. The advantage of our method is that it can smooth out the oscillations in wave functions without losing any information and is potentially a better tool in studying quantum-classical correspondence. In addition, we point out that our method can be used for time-frequency analysis of signals.

Selective solid-phase extraction using oxidized activated carbon modified with triethylenetetramine for preconcentration of metal ions

NASA Astrophysics Data System (ADS)

Zhang, Li; Chang, Xijun; Li, Zhenhua; He, Qun

2010-02-01

A new selective solid-phase extractant using activated carbon as matrix which was purified, oxidized and modified by triethylenetetramine (AC-TETA) was prepared and characterized by FT-IR spectroscopy. At pH 4, quantitative extraction of trace Cr(III), Fe(III) and Pb(II) was obtained and determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Complete elution of the adsorbed metal ions from the sorbent surface was carried out using 0.5 mol L -1 HCl. The maximum static adsorption capacity of sorbent for Cr(III), Fe(III) and Pb(II) was 34.6, 36.5 and 51.9 mg g -1, respectively. The time of quantitative adsorption was less than 2 min. The detection limits of the method was found to be 0.71, 0.35 and 0.45 ng mL -1 for Cr(III), Fe(III) and Pb(II), and the relative standard deviation (RSD) was 3.7%, 2.2% and 2.5%, respectively. Moreover, the method was free from interference with common coexiting ions. The method was also successfully applied to the preconcentration of trace Cr(III), Fe(III) and Pb(II) in synthetic samples and a real sample with satisfactory results.

Drug evaluation: tagatose in the treatment of type 2 diabetes and obesity.

PubMed

Moore, Mary Courtney

2006-10-01

Spherix Inc (formerly Biospherics) is developing tagatose, an orally active lactose derivative for the potential treatment of obesity and type 2 diabetes. The compound is also under investigation for the potential treatment of anemia, hemophilia and medical problems related to infertility, birth weight and excessive maternal food intake. Phase I and II clinical trials have been completed.

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

PubMed

Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

2005-10-01

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

A call for more transparency of registered clinical trials on endometriosis

PubMed Central

Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

2009-01-01

In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

Columbia River Basin Fish and Wildlife Program Annual Implementation Work Plan for Fiscal Year 1994.

DOE Office of Scientific and Technical Information (OSTI.GOV)

United States. Bonneville Power Administration; Northwest Power Planning Council; Columbia Basin Fish and Wildlife Authority

1994-02-01

This document is part of Bonneville Power Administration`s program to protect, mitigate, and enhance fish and wildlife affected by the development and operation of hydroelectric facilities on the Columbia River and its tributaries. The Fiscal Year 1994 (FY 1994) Annual Implementation Work Plan (AIWP) presents Bonneville Power Administration`s (BPA`s) plan for implementation of the Columbia River Basin Fish and Wildlife Program (Program). The purpose of the Program is to guide BPA and other federal agencies in carrying out their responsibilities to protect, mitigate, and enhance fish and wildlife in the Columbia River Basin. Phase I began the work of salmonmore » recovery with certain fast-track measures completed in August 1991. Phase II dealt with Snake and Columbia river flow and salmon harvest and was completed in December 1991. Phase III dealt with system-wide habitat and salmon production issues and was completed in September 1992. Phase IV planning, focusing on resident fish and wildlife, began in August 1993, and was finished and adopted in November 1993. This report provides summaries of the ongoing and new projects for FY 1994 within the areas of juvenile migration, adult migration, salmon harvest, production and habitat, coordinated implementation, monitoring and evaluation, resident fish, and wildlife.« less

HOLIMO II: a digital holographic instrument for ground-based in-situ observations of microphysical properties of mixed-phase clouds

NASA Astrophysics Data System (ADS)

Henneberger, J.; Fugal, J. P.; Stetzer, O.; Lohmann, U.

2013-05-01

Measurements of the microphysical properties of mixed-phase clouds with high spatial resolution are important to understand the processes inside these clouds. This work describes the design and characterization of the newly developed ground-based field instrument HOLIMO II (HOLographic Imager for Microscopic Objects II). HOLIMO II uses digital in-line holography to in-situ image cloud particles in a well defined sample volume. By an automated algorithm, two-dimensional images of single cloud particles between 6 and 250 μm in diameter are obtained and the size spectrum, the concentration and water content of clouds are calculated. By testing the sizing algorithm with monosized beads a systematic overestimation near the resolution limit was found, which has been used to correct the measurements. Field measurements from the high altitude research station Jungfraujoch, Switzerland, are presented. The measured number size distributions are in good agreement with parallel measurements by a fog monitor (FM-100, DMT, Boulder USA). The field data shows that HOLIMO II is capable of measuring the number size distribution with a high spatial resolution and determines ice crystal shape, thus providing a method of quantifying variations in microphysical properties. A case study over a period of 8 h has been analyzed, exploring the transition from a liquid to a mixed-phase cloud, which is the longest observation of a cloud with a holographic device. During the measurement period, the cloud does not completely glaciate, contradicting earlier assumptions of the dominance of the Wegener-Bergeron-Findeisen (WBF) process.

HOLIMO II: a digital holographic instrument for ground-based in situ observations of microphysical properties of mixed-phase clouds

NASA Astrophysics Data System (ADS)

Henneberger, J.; Fugal, J. P.; Stetzer, O.; Lohmann, U.

2013-11-01

Measurements of the microphysical properties of mixed-phase clouds with high spatial resolution are important to understand the processes inside these clouds. This work describes the design and characterization of the newly developed ground-based field instrument HOLIMO II (HOLographic Imager for Microscopic Objects II). HOLIMO II uses digital in-line holography to in situ image cloud particles in a well-defined sample volume. By an automated algorithm, two-dimensional images of single cloud particles between 6 and 250 μm in diameter are obtained and the size spectrum, the concentration and water content of clouds are calculated. By testing the sizing algorithm with monosized beads a systematic overestimation near the resolution limit was found, which has been used to correct the measurements. Field measurements from the high altitude research station Jungfraujoch, Switzerland, are presented. The measured number size distributions are in good agreement with parallel measurements by a fog monitor (FM-100, DMT, Boulder USA). The field data shows that HOLIMO II is capable of measuring the number size distribution with a high spatial resolution and determines ice crystal shape, thus providing a method of quantifying variations in microphysical properties. A case study over a period of 8 h has been analyzed, exploring the transition from a liquid to a mixed-phase cloud, which is the longest observation of a cloud with a holographic device. During the measurement period, the cloud does not completely glaciate, contradicting earlier assumptions of the dominance of the Wegener-Bergeron-Findeisen (WBF) process.

Controlling motion sickness and spatial disorientation and enhancing vestibular rehabilitation with a user-worn see-through display.

PubMed

Krueger, Wesley W O

2011-01-01

An eyewear mounted visual display ("User-worn see-through display") projecting an artificial horizon aligned with the user's head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed. Both phase I and phase II were prospective studies funded by the NIH. The phase II study used repeated measures for motion intolerant subjects and a randomized control group (display device/no display device) pre-posttest design for patients in vestibular rehabilitation. Following technology and display device development, 75 patients were evaluated by test and rating scales in the phase II study; 25 subjects with motion intolerance used the technology in the display device in provocative environments and completed subjective rating scales, whereas 50 patients were evaluated before and after vestibular rehabilitation (25 using the display device and 25 in a control group) using established test measures. All patients with motion intolerance rated the technology as helpful for nine symptoms assessed, and 96% rated the display device as simple and easy to use. Duration of symptoms significantly decreased with use of the technology displayed. In patients undergoing vestibular rehabilitation, there were no significant differences in amount of change from pre- to posttherapy on objective balance tests between display device users and controls. However, those using the technology required significantly fewer rehabilitation sessions to achieve those outcomes than the control group. A user-worn see-through display, utilizing a visual fixation target coupled with a stable artificial horizon and aligned with user movement, has demonstrated substantial benefit for individuals susceptible to motion intolerance and spatial disorientation and those undergoing vestibular rehabilitation. The technology developed has applications in any environment where motion sensitivity affects human performance.

IMATINIB 800MG DAILY INDUCES DEEPER MOLECULAR RESPONSES THAN IMATINIB 400MG DAILY: RESULTS OF SWOG S0325, AN INTERGROUP RANDOMIZED PHASE II TRIAL IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

PubMed Central

Deininger, Michael W.; Kopecky, Kenneth J.; Radich, Jerald P.; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D.; Tallman, Martin; Wadleigh, Martha; Larson, Richard A.; Lipton, Jeffrey H.; Slovak, Marilyn L.; Appelbaum, Frederick R.; Druker, Brian J.

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematologic and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0.038; 3-log reduction: 53% vs. 35%, P=0.049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2.9-fold lower than in the IM400 arm (P=0.010). Complete haematologic response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0.040). Grade 3–4 toxicities were more common for IM800 (58% vs. 31%, P=0.0007), and were most commonly haematologic. Few patients have relapsed, progressed or died, but progression-free (P=0.048) and relapse-free (P=0.031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper molecular responses than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. PMID:24383843

Flipped clinical training: a structured training method for undergraduates in complete denture prosthesis.

PubMed

K, Anbarasi; K, Kasim Mohamed; Vijayaraghavan, Phagalvarthy; Kandaswamy, Deivanayagam

2016-12-01

To design and implement flipped clinical training for undergraduate dental students in removable complete denture treatment and predict its effectiveness by comparing the assessment results of students trained by flipped and traditional methods. Flipped training was designed by shifting the learning from clinics to learning center (phase I) and by preserving the practice in clinics (phase II). In phase I, student-faculty interactive session was arranged to recap prior knowledge. This is followed by a display of audio synchronized video demonstration of the procedure in a repeatable way and subsequent display of possible errors that may occur in treatment with guidelines to overcome such errors. In phase II, live demonstration of the procedure was given. Students were asked to treat three patients under instructor's supervision. The summative assessment was conducted by applying the same checklist criterion and rubric scoring used for the traditional method. Assessment results of three batches of students trained by flipped method (study group) and three traditionally trained previous batches (control group) were taken for comparison by chi-square test. The sum of traditionally trained three batch students who prepared acceptable dentures (score: 2 and 3) and unacceptable dentures (score: 1) was compared with the same of flipped trained three batch students revealed that the number of students who demonstrated competency by preparing acceptable dentures was higher for flipped training (χ 2 =30.996 with p<0.001). The results reveal the supremacy of flipped training in enhancing students competency and hence recommended for training various clinical procedures.

Enantiomeric separation of type I and type II pyrethroid insecticides with different chiral stationary phases by reversed-phase high-performance liquid chromatography.

PubMed

Zhang, Ping; Yu, Qian; He, Xiulong; Qian, Kun; Xiao, Wei; Xu, Zhifeng; Li, Tian; He, Lin

2018-04-01

The enantiomeric separation of type I (bifenthrin, BF) and type II (lambda-cyhalothrin, LCT) pyrethroid insecticides on Lux Cellulose-1, Lux Cellulose-3, and Chiralpak IC chiral columns was investigated by reversed-phase high-performance liquid chromatography. Methanol/water or acetonitrile/water was used as mobile phase at a flow rate of 0.8 mL/min. The effects of chiral stationary phase, mobile phase composition, column temperature, and thermodynamic parameters on enantiomer separation were carefully studied. Bifenthrin got a partial separation on Lux Cellulose-1 column and baseline separation on Lux Cellulose-3 column, while LCT enantiomers could be completely separated on both Lux Cellulose-1 and Lux Cellulose-3 columns. Chiralpak IC provided no separation ability for both BF and LCT. Retention factor (k) and selectivity factor (α) decreased with the column temperature increasing from 10°C to 40°C for both BF and LCT enantiomers. Thermodynamic parameters including ∆H and ∆S were also calculated, and the maximum R s were not always obtained at lowest temperature. Furthermore, the quantitative analysis methods for BF and LCT enantiomers in soil and water were also established. Such results provide a new approach for pyrethroid separation under reversed-phase condition and contribute to environmental risk assessment of pyrethroids at enantiomer level. © 2017 Wiley Periodicals, Inc.

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

Organizational Infrastructure in the Collegiate Athletic Training Setting, Part I: Quality-of-Life Comparisons and Commonalities Among the Models

PubMed Central

Mazerolle, Stephanie M.; Eason, Christianne M.; Goodman, Ashley

2017-01-01

Context: Some anecdotal evidence has suggested that organizational infrastructure may affect the quality of life of athletic trainers (ATs). Objective: To compare ATs' perspectives on work-life balance, role strain, job satisfaction, and retention in collegiate practice settings within the various models. Design: Cross-sectional and qualitative study. Setting: National Collegiate Athletic Association Divisions I, II, and III. Patients or Other Participants: Fifty-nine ATs from 3 models (athletics = 25, medical = 20, academic = 14) completed phase I. A total of 24 ATs (15 men, 9 women), 8 from each model, also completed phase II. Data Collection and Analysis: Participants completed a Web-based survey for phase I and were interviewed via telephone for phase II. Quantitative data were analyzed using statistical software. Likert-scale answers (1 = strongly disagree, 5 = strongly agree) to the survey questions were analyzed using the Kruskal-Wallis, Mann-Whitney U, and Cohen f tests. Qualitative data were evaluated using a general inductive approach. Multiple-analyst triangulation and peer review were conducted to satisfy data credibility. Results: Commonalities were communication, social support, and time management and effective work-life balance strategies. Quantitative data revealed that ATs employed in the athletics model worked more hours (69.6 ± 11.8 hours) than those employed in the medical (57.6 ± 10.2 hours; P = .001) or academic (59.5 ± 9.5 hours; P = .02) model, were less satisfied with their pay (2.68 ± 1.1; χ2 = 7.757, P = .02; f = 0.394), believed that they had less support from their administrators (3.12 ± 1.1; χ2 = 9.512, P = .009; f = 0.443), and had fewer plans to remain in their current positions (3.20 ± 1.2; χ2 = 7.134, P = .03; f = 0.374). Athletic trainers employed in the academic model believed that they had less support from coworkers (3.71 ± 0.90; χ2 = 6.825, P = .03; f = 0.365) and immediate supervisors (3.43 ± 0.90; χ2 = 6.006, P = .050; f = 0.340). No differences in role conflict were found among the models. Conclusions: Organizational infrastructure may play a role in mediating various sources of conflict, but regardless of facilitators, ATs need to be effective communicators, have support networks in place, and possess time-management skills. PMID:27874297

Organizational Infrastructure in the Collegiate Athletic Training Setting, Part I: Quality-of-Life Comparisons and Commonalities Among the Models.

PubMed

Mazerolle, Stephanie M; Eason, Christianne M; Goodman, Ashley

2017-01-01

 Some anecdotal evidence has suggested that organizational infrastructure may affect the quality of life of athletic trainers (ATs).  To compare ATs' perspectives on work-life balance, role strain, job satisfaction, and retention in collegiate practice settings within the various models.  Cross-sectional and qualitative study.  National Collegiate Athletic Association Divisions I, II, and III.  Fifty-nine ATs from 3 models (athletics = 25, medical = 20, academic = 14) completed phase I. A total of 24 ATs (15 men, 9 women), 8 from each model, also completed phase II.  Participants completed a Web-based survey for phase I and were interviewed via telephone for phase II. Quantitative data were analyzed using statistical software. Likert-scale answers (1 = strongly disagree, 5 = strongly agree) to the survey questions were analyzed using the Kruskal-Wallis, Mann-Whitney U, and Cohen f tests. Qualitative data were evaluated using a general inductive approach. Multiple-analyst triangulation and peer review were conducted to satisfy data credibility.  Commonalities were communication, social support, and time management and effective work-life balance strategies. Quantitative data revealed that ATs employed in the athletics model worked more hours (69.6 ± 11.8 hours) than those employed in the medical (57.6 ± 10.2 hours; P = .001) or academic (59.5 ± 9.5 hours; P = .02) model, were less satisfied with their pay (2.68 ± 1.1; χ 2 = 7.757, P = .02; f = 0.394), believed that they had less support from their administrators (3.12 ± 1.1; χ 2 = 9.512, P = .009; f = 0.443), and had fewer plans to remain in their current positions (3.20 ± 1.2; χ 2 = 7.134, P = .03; f = 0.374). Athletic trainers employed in the academic model believed that they had less support from coworkers (3.71 ± 0.90; χ 2 = 6.825, P = .03; f = 0.365) and immediate supervisors (3.43 ± 0.90; χ 2 = 6.006, P = .050; f = 0.340). No differences in role conflict were found among the models.  Organizational infrastructure may play a role in mediating various sources of conflict, but regardless of facilitators, ATs need to be effective communicators, have support networks in place, and possess time-management skills.

Bayesian adaptive phase II screening design for combination trials

PubMed Central

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Background Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Methods Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Results Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. Limitations The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. Conclusions The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial. PMID:23359875

Production assurance program strategy for N Reactor balance of plant systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

House, R.D.; Bitten, E.J.; Keenan, J.P.

1986-03-18

A production assurance program has been established for N Reactor, a dual purpose reactor plant, operated to produce special nuclear materials and steam for electricity. N Reactor, which began operation in December 1963, is now approaching the end of its design life. This paper describes the two phase program for Balance of Plant (BOP) systems. The Phase I evaluation has been completed and indications are that the lifetime of systems and components could be extended by implementing appropriate surveillance, operations and maintenance strategies. In Phase II, a thorough evaluation of components and systems is underway and action items are beingmore » identified which will allow component and system extended operation.« less

Advanced Percussive Drilling Technology for Geothermal Exploration and Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Jiann; Raymond, David; Prasad, Somuri

Percussive hammers are a promising advance in drilling technology for geothermal since they rely upon rock reduction mechanisms that are well-suited for use in the hard, brittle rock characteristic of geothermal formations. The project research approach and work plan includes a critical path to development of a high-temperature (HT) percussive hammer using a two phase approach. The work completed in Phase I of the project demonstrated the viability of percussive hammers and that solutions to technical challenges in design, material technology, and performance are likely to be resolved. Work completed in Phase II focused on testing the findings from Phasemore » I and evaluating performance of the materials and designs at high operating temperatures. A high-operating temperature (HOT) drilling facility was designed, built, and used to test the performance of the DTH under extreme conditions. Results from the testing indicate that a high-temperature capable hammer can be developed and is a viable alternative for use in the driller’s toolbox.« less

Improved nutritional status is related to improved quality of life in Parkinson's disease.

PubMed

Sheard, Jamie M; Ash, Susan; Mellick, George D; Silburn, Peter A; Kerr, Graham K

2014-11-18

Quality of life is poorer in Parkinson's disease than in other conditions and in the general population without Parkinson's disease. Malnutrition also results in poorer quality of life. This study aimed at determining the relationship between quality of life and nutritional status. Community-dwelling people with Parkinson's disease >18 years old were recruited. The Patient-Generated Subjective Global Assessment (PG-SGA) assessed nutritional status. The Parkinson's Disease Questionnaire 39 (PDQ-39) measured quality of life. Phase I was cross-sectional. The malnourished in Phase I were eligible for a nutrition intervention phase, randomised into 2 groups: standard care (SC) with provision of nutrition education materials only and intervention (INT) with individualised dietetic advice and regular weekly follow-up. Data were collected at baseline, 6 weeks, and 12 weeks. Phase I consisted of 120 people who completed the PDQ-39. Phase II consisted of 9 in the SC group and 10 in the INT group. In Phase I, quality of life was poorer in the malnourished, particularly for mobility and activities of daily living domains. There was a significant correlation between PG-SGA and PDQ-39 scores (Phase I, rs = 0.445, p = .000; Phase II, rs = .426, p = .002). In Phase II, no significant difference in the PDQ-39 total or sub-scores was observed between the INT and SC groups; however, there was significant improvement in the emotional well-being domain for the entire group, X2(2) = 8.84, p = .012. Malnourished people with Parkinson's disease had poorer quality of life than the well-nourished, and improvements in nutritional status resulted in quality of life improvements. Attention to nutritional status is an important component of quality of life and therefore the total care of people with Parkinson's disease. ACTRN12610000819022.

Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.

PubMed

Hohloch, Karin; Zeynalova, Samira; Chapuy, Björn; Pfreundschuh, Michael; Loeffler, Markus; Ziepert, Marita; Feller, Alfred C; Trümper, Lorenz; Hasenclever, Dirk; Wulf, Gerald; Schmitz, Norbert

2016-06-01

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study.

PubMed

Martínez, Carmen; Solano, Carlos; Ferrá, Christelle; Sampol, Antonia; Valcárcel, David; Pérez-Simón, José Antonio

2009-05-01

We conducted a phase II trial to investigate the safety and efficacy of alemtuzumab in treating steroid-refractory acute graft-versus-host disease (aGVHD) grade II or higher after stem cell transplantation. Ten adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with complete response and 3 with partial response. Eight infectious events (4 of grade 3-4) and 7 cytomegalovirus (CMV) reactivations were observed. Six patients had grade 3-4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range, 4 to 88 days) after alemtuzumab treatment. Overall, our findings suggest that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

Dye-doped nanostructure polypyrrole film for electrochemically switching solid-phase microextraction of Ni(II) and ICP-OES analysis of waste water.

PubMed

Shamaeli, Ehsan; Alizadeh, Naader

2012-01-01

A nanostructure fiber based on conducting polypyrrole synthesized by an electrochemical method has been developed, and used for electrochemically switching solid-phase microextraction (ES-SPME). The ES-SPME was prepared by the doping of eriochrome blue in polypyrrole (PPy-ECB) and used for selectively extracting the Ni(II) cation in the presence of some transition and heavy metal ions. The cation-exchange behavior of electrochemically prepared polypyrrole on stainless-steel with and without eriochrome blue (ECB) dye was characterized using ICP-OES analysis. The effects of the scan rate for electrochemical synthesis, uptake and the release potential on the extraction behavior of the PPy-ECB conductive fiber were studied. Uptake and release time profiles show that the process of electrically switched cation exchange could be completed within 250 s. The results of the present study point concerning the possibility of developing a selective extraction process for Ni(II) from waste water was explored using such a nanostructured PPy-ECB film through an electrically switched cation exchange. 2012 © The Japan Society for Analytical Chemistry

Near-Term Electric Vehicle Program. Phase II: Mid-Term Summary Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1978-08-01

The Near Term Electric Vehicle (NTEV) Program is a constituent elements of the overall national Electric and Hybrid Vehicle Program that is being implemented by the Department of Energy in accordance with the requirements of the Electric and Hybrid Vehicle Research, Development, and Demonstration Act of 1976. Phase II of the NTEV Program is focused on the detailed design and development, of complete electric integrated test vehicles that incorporate current and near-term technology, and meet specified DOE objectives. The activities described in this Mid-Term Summary Report are being carried out by two contractor teams. The prime contractors for these contractormore » teams are the General Electric Company and the Garrett Corporation. This report is divided into two discrete parts. Part 1 describes the progress of the General Electric team and Part 2 describes the progress of the Garrett team.« less

Rapid determination of ions by combined solid-phase extraction--diffuse reflectance spectroscopy

NASA Technical Reports Server (NTRS)

Fritz, James S.; Arena, Matteo P.; Steiner, Steven A.; Porter, Marc D.

2003-01-01

We introduce colorimetric solid-phase extraction (C-SPE) for the rapid determination of selected ions. This new technique links the exhaustive concentration of an analyte by SPE onto a membrane disk surface for quantitative measurement with a hand-held diffuse reflectance spectrometer. The concentration/measurement procedure is complete in approximately 1 min and can be performed almost anywhere. This method has been used to monitor iodine and iodide in spacecraft water in the 0.1-5.0 ppm range and silver(I) in the range of 5.0-1000 microg/l. Applications to the trace analysis of copper(II), nickel(II), iron(III) and chromium(VI) are described. Studies on the mechanism of extraction showed that impregnation of the disk with a surfactant as well as a complexing reagent results in uptake of additional water, which markedly improves the extraction efficiency.

Threshold-based epidemic dynamics in systems with memory

NASA Astrophysics Data System (ADS)

Bodych, Marcin; Ganguly, Niloy; Krueger, Tyll; Mukherjee, Animesh; Siegmund-Schultze, Rainer; Sikdar, Sandipan

2016-11-01

In this article we analyze an epidemic dynamics model (SI) where we assume that there are k susceptible states, that is a node would require multiple (k) contacts before it gets infected. In specific, we provide a theoretical framework for studying diffusion rate in complete graphs and d-regular trees with extensions to dense random graphs. We observe that irrespective of the topology, the diffusion process could be divided into two distinct phases: i) the initial phase, where the diffusion process is slow, followed by ii) the residual phase where the diffusion rate increases manifold. In fact, the initial phase acts as an indicator for the total diffusion time in dense graphs. The most remarkable lesson from this investigation is that such a diffusion process could be controlled and even contained if acted upon within its initial phase.

Higher Dose Imatinib for Children With De Novo Chronic Phase Chronic Myelogenous Leukemia: A Report From the Children’s Oncology Group

PubMed Central

Champagne, Martin A.; Fu, Cecilia H.; Chang, Myron; Chen, Helen; Gerbing, Robert B.; Alonzo, Todd A.; Cooley, Linda D.; Heerema, Nyla A.; Oehler, Vivian; Wood, Charlotte; French, Mary Ellen; Arceci, Robert J.; Smith, Franklin O.; Bernstein, Mark L.

2016-01-01

Purpose To determine the efficacy of imatinib in children with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML). Methods This was an open label, multi-center phase II clinical trial. Courses were defined as consecutive 28-day intervals. Oral imatinib was administered daily at 340 mg/m2 without interruption in the absence of toxicity. Results Fifty-one children received 978 28-day courses of imatinib. The most common toxicities encountered were hematologic. Forty-one patients (80%) achieved a complete hematologic response by the end of course 2. Nineteen children (38%) obtained a complete cytogenetic response (CCyR) at the end of course 3. Overall, 72% achieved CCyR at a median time of 5.6 months. The rate of complete molecular response (>3 log reduction) was 27%. Progression-free and overall survival at 3 years were 72% ± 6.4% and 92% ± 3.9%, respectively. Conclusions Daily oral imatinib at a dose of 340 mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. PMID:21465636

Capillary Contact Angle in a Completely Wet Groove

NASA Astrophysics Data System (ADS)

Parry, A. O.; Malijevský, A.; Rascón, C.

2014-10-01

We consider the phase equilibria of a fluid confined in a deep capillary groove of width L with identical side walls and a bottom made of a different material. All walls are completely wet by the liquid. Using density functional theory and interfacial models, we show that the meniscus separating liquid and gas phases at two phase capillary coexistence meets the bottom capped end of the groove at a capillary contact angle θcap(L) which depends on the difference between the Hamaker constants. If the bottom wall has a weaker wall-fluid attraction than the side walls, then θcap>0 even though all the isolated walls are themselves completely wet. This alters the capillary condensation transition which is now first order; this would be continuous in a capped capillary made wholly of either type of material. We show that the capillary contact angle θcap(L) vanishes in two limits, corresponding to different capillary wetting transitions. These occur as the width (i) becomes macroscopically large, and (ii) is reduced to a microscopic value determined by the difference in Hamaker constants. This second wetting transition is characterized by large scale fluctuations and essential critical singularities arising from marginal interfacial interactions.

Future of the beam energy scan program at RHIC

NASA Astrophysics Data System (ADS)

Odyniec, Grazyna

2015-05-01

The first exploratory phase of a very successful Beam Energy Scan Program at RHIC was completed in 2014 with Au+Au collisions at energies ranging from 7 to 39 GeV. Data sets taken earlier extended the upper limit of energy range to the √sNN of 200 GeV. This provided an initial look into the uncharted territory of the QCD phase diagram, which is considered to be the single most important graph of our field. The main results from BES phase I, although effected by large statistical errors (steeply increasing with decreasing energy), suggest that the highest potential for discovery of the QCD Critical Point lies bellow √sNN 20 GeV. Here, we discuss the plans and the preparation for phase II of the BES program, with an order of magnitude larger statistics, which is planned for 2018-2019. The BES II will focus on Au+Au collisions at √sNN from 20 to 7 GeV in collider mode, and from √sNN 7 to 3.5 GeV in the fixed target mode, which will be run concurrently with the collider mode operation.

Production, characterization and operation of $$^{76}$$Ge enriched BEGe detectors in GERDA

DOE PAGES

Agostini, M.; Allardt, M.; Andreotti, E.; ...

2015-02-03

The GERmanium Detector Array (Gerda) at the Gran Sasso Underground Laboratory (LNGS) searches for the neutrinoless double beta decay (0νββ) of 76Ge. Germanium detectors made of material with an enriched 76Ge fraction act simultaneously as sources and detectors for this decay. During Phase I of theexperiment mainly refurbished semi-coaxial Ge detectors from former experiments were used. For the upcoming Phase II, 30 new 76 Ge enriched detectors of broad energy germanium (BEGe)-type were produced. A subgroup of these detectors has already been deployed in Gerda during Phase I. The present article reviews the complete production chain of these BEGe detectors including isotopic enrichment,more » purification, crystal growth and diode production. The efforts in optimizing the mass yield and in minimizing the exposure of the 76Ge enriched germanium to cosmic radiation during processing are described. Furthermore, characterization measurements in vacuum cryostats of the first subgroup of seven BEGe detectors and their long-term behavior in liquid argon are discussed. Lastly, the detector performance fulfills the requirements needed for the physics goals of Gerda Phase II.« less

Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.

PubMed

Poklepovic, Andrew; Youssefian, Leena E; Youseffian, Leena; Winning, Mary; Birdsell, Christine A; Crosby, Nancy A; Ramakrishnan, Viswanathan; Ernstoff, Marc S; Roberts, John D

2013-08-01

Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

Nepali, Kunal; Ojha, Ritu; Lee, Hsueh-Yun; Liou, Jing-Ping

2016-08-01

Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.

Environmental Assessment of the Hawaii Geothermal Project Well Flow Test Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1976-11-01

The Hawaii Geothermal Project, a coordinated research effort of the University of Hawaii, funded by the County and State of Hawaii, and ERDA, was initiated in 1973 in an effort to identify, generate, and use geothermal energy on the Big Island of Hawaii. A number of stages are involved in developing geothermal power resources: exploration, test drilling, production testing, field development, power plant and powerline construction, and full-scale production. Phase I of the Project, which began in the summer of 1973, involved conducting exploratory surveys, developing analytical models for interpretation of geophysical results, conducting studies on energy recovery from hotmore » brine, and examining the legal and economic implications of developing geothermal resources in the state. Phase II of the Project, initiated in the summer of 1975, centers on drilling an exploratory research well on the Island of Hawaii, but also continues operational support for the geophysical, engineering, and socioeconomic activities delineated above. The project to date is between the test drilling and production testing phase. The purpose of this assessment is to describe the activities and potential impacts associated with extensive well flow testing to be completed during Phase II.« less

Future of the Beam Energy Scan program at RHIC

DOE PAGES

Odyniec, Grazyna; Bravina, L.; Foka, Y.; ...

2015-05-29

The first exploratory phase of a very successful Beam Energy Scan Program at RHIC was completed in 2014 with Au+Au collisions at energies ranging from 7 to 39 GeV. Data sets taken earlier extended the upper limit of energy range to the √sNN of 200 GeV. This provided an initial look into the uncharted territory of the QCD phase diagram, which is considered to be the single most important graph of our field. The main results from BES phase I, although effected by large statistical errors (steeply increasing with decreasing energy), suggest that the highest potential for discovery of themore » QCD Critical Point lies bellow √sNN 20 GeV. Here, we discuss the plans and the preparation for phase II of the BES program, with an order of magnitude larger statistics, which is planned for 2018-2019. The BES II will focus on Au+Au collisions at √sNN from 20 to 7 GeV in collider mode, and from √sNN 7 to 3.5 GeV in the fixed target mode, which will be run concurrently with the collider mode operation.« less

Nanoparticulate mackinawite formation; a stopped and continuous flow XANES and EXAFS investigation

NASA Astrophysics Data System (ADS)

Butler, I. B.; Bell, A. M.; Charnock, J. M.; Rickard, D.; Vaughan, D. J.; Oldroyd, A.

2009-12-01

The sequestration of sulfur and iron within sedimentary iron sulfides, and ultimately as pyrite, is a major sink in global biogeochemical cycles of those elements and has impacts on global carbon and oxygen cycles. The formation of the metastable black iron (II) monosulfide mackinawite is a key process because mackinawite forms in aqueous solutions where the Fe(II) and S(-II) IAP exceeds mackinawite’s Ksp. Mackinawite is the first formed iron sulfide phase, a consequence of Ostwald’s step rule and is a reactant phase during the formation of thermodynamically stable sedimentary iron sulfide minerals such as pyrite. The reaction of dissolved Fe(II) and sulfide is extremely fast and reactions in the environmentally significant near-neutral pH range tend to completion in <1 second. We have combined stopped and continuous flow techniques with X-ray absorption spectroscopy to evaluate the products of the fast precipitation kinetics of mackinawite over millisecond timescales. EXAFS spectra and data collected during flow experiments were compared with those from a well characterised freeze-dried nanoparticulate mackinawite standard and with published data. Published work has used Rietveld crystal structure refinement to determine bond distances of 2.2558 and 2.5976Å for Fe-S and Fe-Fe respectively. In our experiments Fe K edge XANES is consistent with tetrahedrally coordinated Fe in the precipitated sulfide phase. EXAFS data show that local Fe-S and Fe-Fe coordination and interatomic distances (Fe-S = 2.24Å; Fe-Fe = 2.57Å) are consistent with those determined for the standard mackinawite and published data. The coordination and spacing are developed in the precipitated phase after <10ms reaction at pH5, and considerably faster in experiments at near neutral to alkaline pH. No evidence for phases structurally intermediate between hexaqua Fe(II) and precipitated mackinawite was observed. Aqueous FeS° cluster complexes previously identified as intermediates during mackinawite formation and iron sulfide mineral transformations did not contribute significantly to the EXAFS spectra collected. For environmental, geological and biogeochemical applications, the precipitation of the mineral mackinawite can be considered to proceed rapidly from aqueous Fe(II) and S(-II) ions to the nanoparticulate crystalline mineral. The materials labelled “disordered mackinawite”, or “amorphous FeS” phase which have been widely quoted in the iron sulfide literature do not form at any stage of the precipitation of mackinawite from aqueous solutions. Physical and chemical properties previously ascribed to an amorphous or disordered structure are a consequence of the nanoparticulate form of the first precipitated solid.

Damage Arresting Composites for Shaped Vehicles - Phase II Final Report

NASA Technical Reports Server (NTRS)

Velicki, Alex; Yovanof, Nicolette; Baraja, Jaime; Linton, Kim; Li, Victor; Hawley, Arthur; Thrash, Patrick; DeCoux, Steve; Pickell, Robert

2011-01-01

This report describes the development of a novel structural concept, Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS), that addresses the demanding fuselage loading requirements for the Hybrid Wing or Blended Wing Body (BWB) airplane configuration. In addition to the analytical studies, a three specimen test program was also completed to assess the concept under axial tension loading, axial compression loading, and internal pressure loading.

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR ANALYSIS OF SOIL OR HOUSE DUST SAMPLES USING CHLORPYRIFOS ELISA SAMPLES (BCO-L-1.0)

EPA Science Inventory

This abstract is included for completeness of documentation, but this SOP was not used in the study.

The purpose of this SOP is to describe the procedures for analyzing both Stage II and Stage III soil and vacuum-cleaner collected house dust samples, and Stage III air samples u...

Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature.

PubMed

Alessandro, Pontis; Luigi, Nappi; Felice, Sorrentino; Maria, Paoletti Anna; Benedetto, Melis Gian; Stefano, Angioni

2017-04-01

Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy. Pub Med and Sciencedirect database were searched using terms of "endometriosis treatment", "GnRH antagonist", and "Elagolix". The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles. Five studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed. GnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

Lighting the way: photonics leaders II (PL2) optics and photonics teacher professional development

NASA Astrophysics Data System (ADS)

Gilchrist, Pamela O.; Hilliard-Clark, Joyce; Bowles, Tuere; Carpenter, Eric

2014-07-01

A sample group of nineteen teachers completed the second phase of the Photonics Leaders II Optics and Photonics professional development program. Participants took a basic Physics content knowledge test that was designed by a Professor of Physics. The test was completed before the teachers participated in the program and at the end of the program to gather data for statistical inquiry. Statistical studies on pre-test and post-test data indicated significant gains in physics content knowledge over time, and that instructors teaching at the middle school level or only teaching one subject area scored significantly lower during the pretest. Reports from previous participants are summarized to disseminate the percentage of teachers who have incorporated at least one workshop activity and the kind of activity performed. The concerns and limitations reported by previous participants are reviewed as well.

A novel optic bistable device with very low threshold intensity using photorefractive films

NASA Astrophysics Data System (ADS)

Wang, Sean X.; Sun, Yuankun; Trivedi, Sudhir B.; Li, Guifang

1994-08-01

Brimrose Corporation of America reports the successful completion of the SBIR Phase I research in low-threshold intensity optical bistable devices using photorefractive nonlinearity. A thin photorefractive film optical bistable device was proposed in the Phase I proposal. The feasibility of this device was theoretically investigated. The theoretical feasibility study formulates the materials requirements in such a kind of configuration for Phase II research. In addition, we have proposed and investigated another configuration of optical bistable devices that do not require advanced photorefractive materials, namely, the self-pumped phase conjugator. We have successfully demonstrated a low-threshold optical bistable operation in a KNSBN:CU crystal. To the best of our knowledge, the threshold of 650 mW/sq. cm is the lowest of its kind to be achieved so far.

Efficient and scalable synthesis of bardoxolone methyl (cddo-methyl ester).

PubMed

Fu, Liangfeng; Gribble, Gordon W

2013-04-05

Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ∼50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.

A Hydrostratigraphic Framework Model and Alternatives for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Clark, Lincoln and Nye Counties, Nevada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtel Nevada

2005-09-01

A new, revised three-dimensional (3-D) hydrostratigraphic framework model for Frenchman Flat was completed in 2004. The area of interest includes Frenchman Flat, a former nuclear testing area at the Nevada Test Site, and proximal areas. Internal and external reviews of an earlier (Phase I) Frenchman Flat model recommended additional data collection to address uncertainties. Subsequently, additional data were collected for this Phase II initiative, including five new drill holes and a 3-D seismic survey.

Influence of Coprecipitated Organic Matter on Fe2+(aq) -Catalyzed Transformation of Ferrihydrite: Implications for Carbon Dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chunmei; Kukkadapu, Ravi K.; Sparks, Donald L.

2015-08-10

The poorly crystalline Fe(III) hydroxide ferrihydrite is an important sink for organic matter (OM), nutrients and contaminants in soils and sediments. Aqueous Fe(II) is known to catalyze the transformation of ferrihydrite to more crystalline and thus less reactive phases. While coprecipitation of OM with ferrihydrite could be a common process in many environments due to changes in pH, redox potential or ionic strength, little is known about the impacts of coprecipitated OM on Fe(II)-catalyzed ferrihydrite transformation and its consequences for C dynamics. Accordingly, we explored the extent and pathways of Fe(II)-induced transformation of OM-ferrihydrite coprecipitates and subsequent C mobility. Mössbauermore » spectroscopic results indicated that the coprecipitated OM within ferrihydrite weakened the inter-particle magnetic interactions and decreased average particle size. The coprecipitated OM resulted in diminished Fe(II)-induced ferrihydrite transformation and thus preservation of ferrihydrite. The secondary mineral profiles upon Fe(II) reaction with ferrihydrite were a function of OM content and Fe(II) concentration. At low Fe(II) levels, OM completely inhibited goethite formation and stimulated lepidocrocite formation. At high Fe(II) levels, whereas goethite was formed in the presence of OM, OM reduced the amount of goethite and magnetite formation and increased the formation of lepidocrcocite. The solid-phase C content remained unchanged after reaction, while OM desorpability by H2PO4- was enhanced following reaction of OM-ferrihydrites with aqueous Fe(II). These findings provide insights into the reactivity of natural ferrihydrite containing OM in soils and sediments and the subsequent impact on mineral evolution and C dynamics.« less

Mixed ligand two dimensional Cd(ii)/Ni(ii) metal organic frameworks containing dicarboxylate and tripodal N-donor ligands: Cd(ii) MOF is an efficient luminescent sensor for detection of picric acid in aqueous media.

PubMed

Rachuri, Yadagiri; Parmar, Bhavesh; Bisht, Kamal Kumar; Suresh, Eringathodi

2016-05-04

Two dimensional metal organic frameworks (MOFs) [Cd(5-BrIP)(TIB)]n () and [Ni2(5-BrIP)2(TIB)2]n (), involving the aromatic polycarboxylate ligand 5-bromo isophthalic acid (H2BrIP), flexible tripodal ligand 1,3,5-tris(imidazol-1-ylmethyl)benzene (TIB) and Cd(ii)/Ni(ii) metal nodes have been synthesized by different methods. These compounds were characterized by various analytical methods, and variable temperature X-ray diffraction data showed thermal stability of both MOFs up to 350 °C. Phase purity as well as water stability of the MOFs were established by powder X-ray diffraction, and the structural diversity of the compounds were investigated by single-crystal X-ray diffraction. Both the MOFs are mixed ligand 2D nets, and the topology of the network can be described as a binodal 3,5-c connected net with 3,5L2 topology having the point symbol {4(2)·6(7)·8}{4(2)·6}. Sensing of picric acid [2,4,6-trinitrophenol, TNP] by luminescence quenching among a large range of nitroanalytes in aqueous phase by the Cd(ii) luminescent MOF (LMOF) were been investigated. Structural studies on 1 : 1 co-crystals () of TIB and TNP were carried out. The selective and sensitive fluorescence quenching response of towards electron-deficient TNP over other nitro analytes in aqueous phase was demonstrated by fluorescence quenching titration. Concomitant occurrence of electron transfer/energy transfer processes and electrostatic interaction favours the selective sensing of TNP. A Cd(ii) LMOF ()-coated paper strip that we developed demonstrated fast and selective response to TNP, by the complete quenching of the blue fluorescence upon excitation of the paper strip at 365 nm radiation in its presence.

COMMERCIALIZATION OF AN ATMOSPHERIC IRON-BASED CDCL PROCESS FOR POWER PRODUCTION. PHASE I: TECHNOECONOMIC ANALYSIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vargas, Luis

Coal Direct Chemical Looping (CDCL) is an advanced oxy-combustion technology that has potential to enable substantial reductions in the cost and energy penalty associated with carbon dioxide (CO2) capture from coal-fired power plants. Through collaborative efforts, the Babcock & Wilcox Power Generation Group (B&W) and The Ohio State University (OSU) developed a conceptual design for a 550 MWe (net) supercritical CDCL power plant with greater than 90% CO2 capture and compression. Process simulations were completed to enable an initial assessment of its technical performance. A cost estimate was developed following DOE’s guidelines as outlined in NETL’s report “Quality Guidelines formore » Energy System Studies: Cost Estimation Methodology for NETL Assessments of Power Plant Performance”, (2011/1455). The cost of electricity for the CDCL plant without CO2 Transportation and Storage cost resulted in $ $102.67 per MWh, which corresponds to a 26.8 % increase in cost of electricity (COE) when compared to an air-fired pulverized-coal supercritical power plant. The cost of electricity is strongly depending on the total plant cost and cost of the oxygen carrier particles. The CDCL process could capture further potential savings by increasing the performance of the particles and reducing the plant size. During the techno-economic analysis, the team identified technology and engineering gaps that need to be closed to bring the technology to commercialization. The technology gaps were focused in five critical areas: (i) moving bed reducer reactor, (ii) fluidized bed combustor, (iii) particle riser, (iv) oxygen-carrier particle properties, and (v) process operation. The key technology gaps are related to particle performance, particle manufacturing cost, and the operation of the reducer reactor. These technology gaps are to be addressed during Phase II of project. The project team is proposing additional lab testing to be completed on the particle and a 3MWth pilot facility be built to evaluate the reducer reactor performance among other aspects of the technology. A Phase II proposal was prepared and submitted to DOE. The project team proposed a three year program in Phase II. Year 1 includes lab testing and particle development work aimed at improving the chemical and mechanical properties of the oxygen carrier particle. In parallel, B&W will design the 3MWt pilot plant. Any improvements to the particle performance discovered in year 1 that would impact the design of the pilot will be incorporated into the final design. Year 2 will focus on procurement of materials and equipment, and construction of the pilot plant. Year 3 will include, commissioning, start-up, and testing in the pilot. Phase I work was successfully completed and a design and operating philosophy for a 550 MWe commercial scale coal-direct chemical looping power plant was developed. Based on the results of the techno-economic evaluation, B&W projects that the CDCL process can achieve 96.5% CO2 capture with a« less

Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms.

PubMed

Albrecht, Helmut; Vernon, Margaret; Solomon, Gail

2012-12-27

Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study. The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient's End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study. Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated. Results from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of mucoactive drugs. The study was registered with clinicaltrials.gov (NCT01046136).

Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms

PubMed Central

2012-01-01

Background Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study. Methods The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient’s End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study. Results Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated. Conclusions Results from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of mucoactive drugs. Trial registration The study was registered with clinicaltrials.gov (NCT01046136). PMID:23270519

Evaluating depressive symptoms in hypomanic and manic episodes using a structured diagnostic tool: validation of a new Mini International Neuropsychiatric Interview (M.I.N.I.) module for the DSM-5 'With Mixed Features' specifier.

PubMed

Hergueta, Thierry; Weiller, Emmanuelle

2013-01-01

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), includes a new 'With Mixed Features' specifier for mood episodes. In (hypo-)manic episodes, the specifier is given if three or more depressive symptoms are present nearly every day during the episode. A new module of the Mini International Neuropsychiatric Interview (M.I.N.I.) has been developed as a patient-completed questionnaire to evaluate the DSM-5 specifier for (hypo-)manic episodes. The objective of this study was to validate this new module. In Phase I, patients with a manic episode in the past 6 months completed the module and were asked whether the wording was clear, understandable, relevant and specific. Based on their feedback, the module was refined and finalised. In Phase II, psychiatrists each invited five patients to complete the module. The psychiatrists completed record forms for these five patients, which included their diagnoses, made according to DSM-5 criteria during clinical interviewing. The module was validated by comparing depressive symptoms reported by the patients themselves using the M.I.N.I. module with those evaluated by their psychiatrist using DSM-5 criteria during clinical interviewing. In Phase I, a few changes were made to the M.I.N.I. module based on feedback from 20 patients (60% of whom had mixed features). In Phase II, 23 psychiatrists completed record forms for 115 patients, 99 (86.1%) of whom completed the M.I.N.I. module. Agreement between psychiatrists' DSM-5 diagnoses and patients' M.I.N.I. responses was substantial (Cohen's kappa coefficient, 0.60). The overall sensitivity of the M.I.N.I. was 0.91 and its specificity was 0.70. Sensitivity ranged from 0.63 for psychomotor retardation to 0.90 for suicidal thoughts. Specificity ranged from 0.63 for diminished interest/pleasure to 0.90 for suicidal thoughts. The module's positive and negative predictive values were 0.72 and 0.90, respectively. In summary, the M.I.N.I. module demonstrated good concurrent validity with psychiatrists' evaluation of DSM-5 mixed features in manic patients, accurately detecting mixed features with limited risk of over-diagnosis. Due to its simplicity, the M.I.N.I. module could be incorporated into routine psychiatric evaluation of patients with manic episodes. It could also provide a valuable standardised tool for clinical and epidemiological research.

Using phase II data for the analysis of phase III studies: An application in rare diseases.

PubMed

Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

2017-06-01

Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.

Virulizin.

PubMed

2002-01-01

Virulizin, a biological response modifier, is a mixture of proteins and peptides that have been extracted from bovine reticuloendothelial tissue that activates macrophages. It is being developed by Lorus Therapeutics (formerly Imutec Pharma) for the treatment of various cancers and had completed phase II clinical trials in Canada for the treatment of pancreatic cancer and advanced malignant melanoma. The commencement of phase III clinical trials in Canada, for the treatment of pancreatic cancer, was delayed due to quality control problems with batches of virulizin and all clinical trials of virulizin were suspended as Lorus underwent a major restructuring programme. However, phase I/II clinical trials are now underway again in Canada in HIV-positive patients with Kaposi's sarcoma and for the treatment of pancreatic cancer. A phase I/II clinical trial is also underway in patients with pancreatic cancer in the USA. Lorus announced in June 2000 that it had completed a meta analysis of three phase I/II studies of virulizin that showed the drug increased survival and improved quality of life for pancreatic cancer patients. Based on these positive results, Lorus initiated a phase III trial to be conducted at 40 sites in North America in November 2001. The study aims to enrol 350 patients with advanced pancreatic cancer and will test the effectiveness of virulizin as first- and second-line treatment of pancreatic cancer. The study will compare virulizin + gemcitabine with gemcitabine alone as first-line therapy, while second-line treatment will involve patients who have failed to respond to gemcitabine. Some of these patients will receive virulizin + fluorouracil while another group will receive only fluorouracil. The study is scheduled to complete in 2004 or early 2005. Virulizin received orphan drug status for this indication from the US FDA in February 2001. Lorus received fast track designation from the FDA in June 2002 for virulizin for the treatment of pancreatic cancer. Virulizin is registered for the treatment of malignant melanoma in Mexico and is due to be launched there in 2002. Lorus has entered into an exclusive 7-year distribution agreement with Faulding Canada Inc., giving Faulding (now part of Mayne Group) the right to market and sell virulizin in Mexico for the treatment of melanoma. Lorus will receive royalties from sales of the product and will be responsible for its manufacture. In April 2002, Mayne exercised its option to acquire the distribution rights for virulizin in Brazil. Lorus Therapeutics has signed a collaborative agreement with NaPro BioTherapeutics, USA, to study the efficacy of virulizin in combination with paclitaxel for the treatment of lung adenocarcinoma. Lorus is conducting preclinical studies of virulizin in human breast cancer, lung, ovarian and prostate cancer, and has reported successful activity of the agent in these indications. Lorus was awarded a patent by the US Patent and Trademark Office to protect the only known process used to create virulizin. This patent, in conjunction with the patents issued in Australia, South Africa, New Zealand, Korea and Singapore, broadens and strengthens the protection of Lorus' intellectual property rights regarding the process, composition and use of virulizin.

PHP-HT (VitaResc Biotech).

PubMed

Baldwin, A; Wiley, E

2001-04-01

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

Project Northland high school interventions: community action to reduce adolescent alcohol use.

PubMed

Perry, C L; Williams, C L; Komro, K A; Veblen-Mortenson, S; Forster, J L; Bernstein-Lachter, R; Pratt, L K; Dudovitz, B; Munson, K A; Farbakhsh, K; Finnegan, J; McGovern, P

2000-02-01

Project Northland is a randomized community trial initially implemented in 24 school districts and communities in northeastern Minnesota, with goals of delaying onset and reducing adolescent alcohol use using community-wide, multiyear, multiple interventions. The study targets the Class of 1998 from the 6th to 12th grades (1991-1998). The early adolescent phase of Project Northland has been completed, and reductions in the prevalence of alcohol use at the end of 8th grade were achieved. Phase II of Project Northland, targeting 11th- and 12th-grade students, uses five major strategies: (1) direct action community organizing methods to encourage citizens to reduce underage access to alcohol, (2) youth development involving high school students in youth action teams, (3) print media to support community organizing and youth action initiatives and communicate healthy norms about underage drinking (e.g., providing alcohol to minors is unacceptable), (4) parent education and involvement, and (5) a classroom-based curriculum for 11th-grade students. This article describes the background, design, implementation, and process measures of the intervention strategies for Phase II of Project Northland.

The VRT gas turbine combustor - Phase II

NASA Technical Reports Server (NTRS)

Melconian, Jerry O.; Mongia, Hukam C.; Nguyen, Hung L.

1992-01-01

An innovative annular combustor configuration is being developed for aircraft and other gas turbine engines. This design has the potential of permitting higher turbine inlet temperatures by reducing the pattern factor and providing a major reduction in NO(x) emission. The design concept is based on a Variable Residence Time (VRT) technique which allows large fuel particles adequate time to completely burn in the circumferentially mixed primary zone. High durability of the combustor is achieved by dual-function use of the incoming air. In Phase I, the feasibility of the concept was demonstrated by water analogue tests and 3D computer modeling. The flow pattern within the combustor was as predicted. The VRT combustor uses only half the number of fuel nozzles of the conventional configuration. In Phase II, hardware was designed, procured, and tested under conditions simulating typical supersonic civil aircraft cruise conditions to the limits of the rig. The test results confirmed many of the superior performance predictions of the VRT concept. The Hastelloy X liner showed no signs of distress after nearly six hours of tests using JP5 fuel.

The NDCX-II engineering design

NASA Astrophysics Data System (ADS)

Waldron, W. L.; Abraham, W. J.; Arbelaez, D.; Friedman, A.; Galvin, J. E.; Gilson, E. P.; Greenway, W. G.; Grote, D. P.; Jung, J.-Y.; Kwan, J. W.; Leitner, M.; Lidia, S. M.; Lipton, T. M.; Reginato, L. L.; Regis, M. J.; Roy, P. K.; Sharp, W. M.; Stettler, M. W.; Takakuwa, J. H.; Volmering, J.; Vytla, V. K.

2014-01-01

The Neutralized Drift Compression Experiment (NDCX-II) is a user facility located at Lawrence Berkeley National Laboratory which is uniquely designed for ion-beam-driven high energy density laboratory physics and heavy ion fusion research. Construction was completed in March 2012 and the facility is now in the commissioning phase. A significant amount of engineering was carried out in order to meet the performance parameters required for a wide range of target heating experiments while making the most cost-effective use of high-value hardware available from a decommissioned high current electron induction accelerator. The technical challenges and design of this new ion induction accelerator facility are described.

EUPDF-II: An Eulerian Joint Scalar Monte Carlo PDF Module : User's Manual

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, Nan-Suey (Technical Monitor)

2004-01-01

EUPDF-II provides the solution for the species and temperature fields based on an evolution equation for PDF (Probability Density Function) and it is developed mainly for application with sprays, combustion, parallel computing, and unstructured grids. It is designed to be massively parallel and could easily be coupled with any existing gas-phase CFD and spray solvers. The solver accommodates the use of an unstructured mesh with mixed elements of either triangular, quadrilateral, and/or tetrahedral type. The manual provides the user with an understanding of the various models involved in the PDF formulation, its code structure and solution algorithm, and various other issues related to parallelization and its coupling with other solvers. The source code of EUPDF-II will be available with National Combustion Code (NCC) as a complete package.

Phase I/II Clinical Trial of Hyaluronan-Cisplatin Nanoconjugate for the Treatment of Spontaneous Canine Cancers

PubMed Central

Cai, Shuang; Zhang, Ti; Forrest, W.C.; Yang, Qiuhong; Groer, Chad; Mohr, Eva; Aires, Daniel J.; Axiak-Bechtel, Sandra M.; Flesner, Brian K.; Henry, Carolyn J.; Selting, Kimberly A.; Tate, Deborah; Swarz, Jeffrey A.; Bryan, Jeffrey N.; Forrest, M. Laird

2015-01-01

Objective To conduct an open label, multi-dose Phase I/II clinical study in spontaneous canine cancers and evaluate the pharmacokinetics, safety, and efficacy of the hyaluronan-based cisplatin formulation (HA-Pt). Animals 13 dogs with heterogeneous, naturally occurring cancers. Procedures The dogs received up to four injections of 10-30 mg/m2 HA-Pt into the tumor or peritumoral sub-mucosa at three-week intervals. Blood sample (2 mL) was collected from the jugular catheter at 0.5, 1, 2, 4, and 24 hours following drug administration. A complete blood count and renal profile with urinalysis were conducted prior to and one week after each treatment. Tumor measurements were collected three weeks following each administration to assess response. Results Of the 13 dogs with heterogeneous, naturally occurring cancers, 23% had complete response and 15% had partial response or stable disease. Among the dogs that received drug with low diaquated content, the complete response rate for SCC was 3/7 (43%). Myelosuppression and cardiac toxicity were observed for 38% and 19% of the dogs, respectively. The formulation did not cause nephrotoxicity, the dose-limiting toxicity of standard cisplatin, in any dogs. Conclusions and Clinical Relevance The HA-Pt formulation demonstrated positive response in spontaneous canine squamous cell carcinomas. It did not cause nephrotoxicity in any patients. Canine oral SCC is very homogenous in progression and drug response to human HNSCC, and these results could be useful in developing human treatments. PMID:27580113

Evaluation of diatomea algae Thalassiosira weissflogii sensitivity to chloride mercury and methylmercury by chlorophyll fluorescence analysis

NASA Astrophysics Data System (ADS)

Graevskaya, E. E.; Antal, T. K.; Matorin, D. N.; Voronova, E. N.; Pogosyan, S. I.; Rubin, A. B.

2003-05-01

Measurement of chlorophyll fluorescence has been shown to be a rapid, non-invasive, and reliable method to assess photosynthetic performance in a changing environment. In our study, the pulseamplitude-modulation (PAM) - fluorometric method was used to evaluate the sensitivity to chloride mercury and methylmercury chloride of diatomea microalgae Thalassiosira weissflogii. We found that 10^{-6} and 10^{-7} M MeHg led to a slow decrease in the PS II activity following for prolonged lag phase, whereas the algae was not sensitive to the same concentrations of HgCl2. However observed PS II inactivation by methylmercury was not complete and about 10 percents ofthe cells kept the high level of PS II activity as it was shown by microfluorometric analysis. These cells could determine adaptation of algae to methylmercury effect. Both toxicants decreased the rate of PS II reparation, as well as increased a heat pathway of excitation dissipation in PS II antennae complex.

Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

2017-12-01

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

William C. Maurer; William J. McDonald; Thomas E. Williams

Underbalanced drilling is experiencing growth at a rate that rivals that of horizontal drilling in the mid-1980s and coiled-tubing drilling in the 1990s. Problems remain, however, for applying underbalanced drilling in a wider range of geological settings and drilling environments. This report addresses developments under this DOE project to develop products aimed at overcoming these problems. During Phase I of the DOE project, market analyses showed that up to 12,000 wells per year (i.e., 30% of all wells) will be drilled underbalanced in the U.S.A. within the next ten years. A user-friendly foam fluid hydraulics model (FOAM) was developed formore » a PC Windows environment during Phase I. FOAM predicts circulating pressures and flow characteristics of foam fluids used in underbalanced drilling operations. FOAM is based on the best available mathematical models, and was validated through comparison to existing models, laboratory test data and field data. This model does not handle two-phase flow or air and mist drilling where the foam quality is above 0.97. This FOAM model was greatly expanded during Phase II including adding an improved foam rheological model and a ''matching'' feature that allows the model to be field calibrated. During Phase I, a lightweight drilling fluid was developed that uses hollow glass spheres (HGS) to reduce the density of the mud to less than that of water. HGS fluids have several advantages over aerated fluids, including they are incompressible, they reduce corrosion and vibration problems, they allow the use of mud-pulse MWD tools, and they eliminate high compressor and nitrogen costs. Phase II tests showed that HGS significantly reduce formation damage with water-based drilling and completion fluids and thereby potentially can increase oil and gas production in wells drilled with water-based fluids. Extensive rheological testing was conducted with HGS drilling and completion fluids during Phase II. These tests showed that the HGS fluids act similarly to conventional fluids and that they have potential application in many areas, including underbalanced drilling, completions, and riserless drilling. Early field tests under this project are encouraging. These led to limited tests by industry (which are also described). Further field tests and cost analyses are needed to demonstrate the viability of HGS fluids in different applications. Once their effectiveness is demonstrated, they should find widespread application and should significantly reduce drilling costs and increase oil and gas production rates. A number of important oilfield applications for HGS outside of Underbalanced Drilling were identified. One of these--Dual Gradient Drilling (DGD) for deepwater exploration and development--is very promising. Investigative work on DGD under the project is reported, along with definition of a large joint-industry project resulting from the work. Other innovative products/applications are highlighted in the report including the use of HGS as a cement additive.« less

47 CFR 54.309 - Connect America Fund Phase II Public Interest Obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund Phase II Public Interest Obligations. 54.309 Section 54.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... Connect America Fund Phase II Public Interest Obligations. (a) A price cap carrier electing Phase II model...

Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia.

PubMed

Deininger, Michael W; Kopecky, Kenneth J; Radich, Jerald P; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D; Tallman, Martin; Wadleigh, Martha; Larson, Richard A; Lipton, Jeffrey H; Slovak, Marilyn L; Appelbaum, Frederick R; Druker, Brian J

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukaemia (CP-CML) is 400 mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematological and cytogenetic response to IM400 vs. imatinib 400 mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P = 0·038; 3-log reduction: 53% vs. 35%, P = 0·049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2·9-fold lower than in the IM400 arm (P = 0·010). Complete haematological response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P = 0·040). Grade 3-4 toxicities were more common for IM800 (58% vs. 31%, P = 0·0007), and were most commonly haematological. Few patients have relapsed, progressed or died, but both progression-free (P = 0·048) and relapse-free (P = 0·031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper MRs than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. © 2013 John Wiley & Sons Ltd.

Virtual reality bringing a new reality to postthoracotomy lung cancer patients via a home-based exercise intervention targeting fatigue while undergoing adjuvant treatment.

PubMed

Hoffman, Amy J; Brintnall, Ruth Ann; Brown, Jean K; von Eye, Alexander; Jones, Lee W; Alderink, Gordon; Ritz-Holland, Deborah; Enter, Mark; Patzelt, Lawrence H; VanOtteren, Glenn M

2014-01-01

Little is known about rehabilitation for postthoracotomy non-small cell lung cancer (NSCLC) patients. This research uses a perceived self-efficacy-enhancing light-intensity exercise intervention targeting a priority symptom, cancer-related fatigue (CRF), for postthoracotomy NSCLC patients. This article reports on phase II of a 2-phase study. Phase I focused on initiation and tolerance of exercise during the 6 weeks immediately after thoracotomy, whereas phase II addressed maintenance of exercise for an additional 10 weeks including participants initiating and completing chemotherapy and/or radiation therapy. The objective of this study was to investigate the feasibility, acceptability, and preliminary efficacy of an exercise intervention for postthoracotomy NSCLC patients to include those initiating and completing adjuvant therapy. A single-arm design composed of 7 participants postthoracotomy for NSCLC performed light-intensity exercises using an efficacy-enhancing virtual-reality approach using the Nintendo Wii Fit Plus. Despite most participants undergoing chemotherapy and/or radiation therapy, participants adhered to the intervention at a rate of 88% with no adverse events while giving the intervention high acceptability scores on conclusion. Likewise, participants' CRF scores improved from initiation through the conclusion of the intervention with perceived self-efficacy for walking at a light intensity continuously for 60 minutes, improving significantly upon conclusion over presurgery values. Postthoracotomy NSCLC patients maintained exercise for an additional 10 weeks while undergoing adjuvant therapy showing rehabilitation potential because the exercise intervention was feasible, safe, well tolerated, and highly acceptable showing positive changes in CRF self-management. A randomized controlled trial is needed to further investigate these relationships.

Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

PubMed

Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

2015-07-10

In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50% prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial. NCT01675999 (ClinicalTrials.gov).

Modeling Code Is Helping Cleveland Develop New Products

NASA Technical Reports Server (NTRS)

1998-01-01

Master Builders, Inc., is a 350-person company in Cleveland, Ohio, that develops and markets specialty chemicals for the construction industry. Developing new products involves creating many potential samples and running numerous tests to characterize the samples' performance. Company engineers enlisted NASA's help to replace cumbersome physical testing with computer modeling of the samples' behavior. Since the NASA Lewis Research Center's Structures Division develops mathematical models and associated computation tools to analyze the deformation and failure of composite materials, its researchers began a two-phase effort to modify Lewis' Integrated Composite Analyzer (ICAN) software for Master Builders' use. Phase I has been completed, and Master Builders is pleased with the results. The company is now working to begin implementation of Phase II.

HPC Access Using KVM over IP

DTIC Science & Technology

2007-06-01

these devices coupled with the difficulties- working with IP Video Systems (formerly Teraburst and cost-of installing dedicated long-distance fiber optic...dedicated fiber is best revealed that the IP Video Systems solutions seem to be suited for installation for point-to-point communications. the best...Research completion of the SBIR Phase II effort is planned for late (SBIR) effort with IP Video Systems (formerly known as FY 07. This paper will discuss

Webcam delivery of the Camperdown Program for adolescents who stutter: a phase II trial.

PubMed

Carey, Brenda; O'Brian, Sue; Lowe, Robyn; Onslow, Mark

2014-10-01

This Phase II clinical trial examined stuttering adolescents' responsiveness to the Webcam-delivered Camperdown Program. Sixteen adolescents were treated by Webcam with no clinic attendance. Primary outcome was percentage of syllables stuttered (%SS). Secondary outcomes were number of sessions, weeks and hours to maintenance, self-reported stuttering severity, speech satisfaction, speech naturalness, self-reported anxiety, self-reported situation avoidance, self-reported impact of stuttering, and satisfaction with Webcam treatment delivery. Data were collected before treatment and up to 12 months after entry into maintenance. Fourteen participants completed the treatment. Group mean stuttering frequency was 6.1 %SS (range, 0.7-14.7) pretreatment and 2.8 %SS (range, 0-12.2) 12 months after entry into maintenance, with half the participants stuttering at 1.2 %SS or lower at this time. Treatment was completed in a mean of 25 sessions (15.5 hr). Self-reported stuttering severity ratings, self-reported stuttering impact, and speech satisfaction scores supported %SS outcomes. Minimal anxiety was evident either pre- or post-treatment. Individual responsiveness to the treatment varied, with half the participants showing little reduction in avoidance of speech situations. The Webcam service delivery model was appealing to participants, although it was efficacious and efficient for only half. Suggestions for future stuttering treatment development for adolescents are discussed.

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

PubMed

Michael, M; Chander, S; McKendrick, J; MacKay, J R; Steel, M; Hicks, R; Heriot, A; Leong, T; Cooray, P; Jefford, M; Zalcberg, J; Bressel, M; McClure, B; Ngan, S Y

2014-11-11

Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Isac Sc-Linac Phase-II Helium Refrigerator Commissioning and First Operational Experience at Triumf

NASA Astrophysics Data System (ADS)

Sekachev, I.; Kishi, D.; Laxdal, R. E.

2010-04-01

ISAC Phase-II is an upgrade of the radioactive isotope superconducting linear accelerator, SC-linac, at TRIUMF. The Phase-I section of the accelerator, medium-beta, is operational and is cooled with a 600 W helium refrigerator, commissioned in March 2005. An identical refrigerator is being used with the Phase-II segment of the accelerator; which is now under construction. The second refrigerator has been commissioned and tested with the Phase-I section of the linac and is used for Phase-II linac development, including new SC-cavity performance tests. The commissioning of the Phase-II refrigeration system and recent operational experience is presented.

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

78 FR 76789 - Additional Connect America Fund Phase II Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... inspection and copying during normal business hours in the FCC Reference Information Center, Portals II, 445... Phase I to Phase II. 2. Timing of Phase II Support Disbursements. In the USF/ICC Transformation Order... language in paragraph 180 of the USF/ICC Transformation Order. We now seek to more fully develop the record...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

Chromosomal DNA Deletions Explain Phenotypic Characteristics of Two Antigenic Variants, Phase II and RSA 514 (Crazy), of the Coxiella burnetii Nine Mile Strain†

PubMed Central

Hoover, T. A.; Culp, D. W.; Vodkin, M. H.; Williams, J. C.; Thompson, H. A.

2002-01-01

After repeated passages through embyronated eggs, the Nine Mile strain of Coxiella burnetii exhibits antigenic variation, a loss of virulence characteristics, and transition to a truncated lipopolysaccharide (LPS) structure. In two independently derived strains, Nine Mile phase II and RSA 514, these phenotypic changes were accompanied by a large chromosomal deletion (M. H. Vodkin and J. C. Williams, J. Gen. Microbiol. 132:2587-2594, 1986). In the work reported here, additional screening of a cosmid bank prepared from the wild-type strain was used to map the deletion termini of both mutant strains and to accumulate all the segments of DNA that comprise the two deletions. The corresponding DNAs were then sequenced and annotated. The Nine Mile phase II deletion was completely nested within the deletion of the RSA 514 strain. Basic alignment and homology studies indicated that a large group of LPS biosynthetic genes, arranged in an apparent O-antigen cluster, was deleted in both variants. Database homologies identified, in particular, mannose pathway genes and genes encoding sugar methylases and nucleotide sugar epimerase-dehydratase proteins. Candidate genes for addition of sugar units to the core oligosaccharide for synthesis of the rare sugar 6-deoxy-3-C-methylgulose (virenose) were identified in the deleted region. Repeats, redundancies, paralogous genes, and two regions with reduced G+C contents were found within the deletions. PMID:12438347

Capability of Rolling Efficiency for 100M High-Speed Rails

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Howard

2014-03-22

OG Technologies, Inc. (OGT), along with its academic and industrial partners, proposes this CORE project for the Capability of Rolling Efficiency for 100m high-speed rails. The goal is to establish the competitive advantage, and thus the sustainability of the US-based rail manufacturers by greatly enhanced efficiency through innovative in-line metrology technology, in-depth process knowledge, and advanced process control to overcome detrimental factors such as higher labor costs that are saddling the US manufacturing sector. This Phase I project was carried out by an industrial-academia team over 9 months. The R&D team successfully completed all technical tasks and accomplished the objectivesmore » for the Phase I. In addition to the technical efforts, the introductory information of this project as well as anticipated progress was disseminated to steel mills interested in the project. The Phase I project has established the technical and commercial basis for additional development. There are needs to further completing the in-line sensing capability, deepening the capability of metamodeling, and supporting the process monitoring and control. The R&D team plans to submit a Phase II proposal based on the findings.« less

Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward.

PubMed

Guy, Bruno; Briand, Olivier; Lang, Jean; Saville, Melanie; Jackson, Nicholas

2015-12-10

Sanofi Pasteur has developed a recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is in late-stage development. The present review summarizes the different steps in the development of this dengue vaccine, with a particular focus on the clinical data from three efficacy trials, which includes one proof-of-concept phase IIb (NCT00842530) and two pivotal phase III efficacy trials (NCT01373281 and NCT01374516). Earlier studies showed that the CYD-TDV candidate had a satisfactory safety profile and was immunogenic across the four vaccine serotypes in both in vitro and in vivo preclinical tests, as well as in initial phase I to phase II clinical trials in both flavivirus-naïve and seropositive individuals. Data from the 25 months (after the first injection) active phase of the two pivotal phase III efficacy studies shows that CYD-TDV (administered at 0, 6, and 12 months) is efficacious against virologically-confirmed disease (primary endpoint) and has a good safety profile. Secondary analyses also showed efficacy against all four dengue serotypes and protection against severe disease and hospitalization. The end of the active phases in these studies completes more than a decade of development of CYD-TDV, but considerable activities and efforts remain to address outstanding scientific, clinical, and immunological questions, while preparing for the introduction and use of CYD-TDV. Additional safety observations were recently reported from the first complete year of hospital phase longer term surveillance for two phase 3 studies and the first and second completed years for one phase 2b study, demonstrating the optimal age for intervention from 9 years. Dengue is a complex disease, and both short-term and long-term safety and efficacy will continue to be addressed by ongoing long-term follow-up and future post-licensure studies. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

PubMed

Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

2016-11-15

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

Background-free search for neutrinoless double-β decay of 76Ge with GERDA.

PubMed

2017-04-05

Many extensions of the Standard Model of particle physics explain the dominance of matter over antimatter in our Universe by neutrinos being their own antiparticles. This would imply the existence of neutrinoless double-β decay, which is an extremely rare lepton-number-violating radioactive decay process whose detection requires the utmost background suppression. Among the programmes that aim to detect this decay, the GERDA Collaboration is searching for neutrinoless double-β decay of 76 Ge by operating bare detectors, made of germanium with an enriched 76 Ge fraction, in liquid argon. After having completed Phase I of data taking, we have recently launched Phase II. Here we report that in GERDA Phase II we have achieved a background level of approximately 10 -3 counts keV -1 kg -1 yr -1 . This implies that the experiment is background-free, even when increasing the exposure up to design level. This is achieved by use of an active veto system, superior germanium detector energy resolution and improved background recognition of our new detectors. No signal of neutrinoless double-β decay was found when Phase I and Phase II data were combined, and we deduce a lower-limit half-life of 5.3 × 10 25 years at the 90 per cent confidence level. Our half-life sensitivity of 4.0 × 10 25 years is competitive with the best experiments that use a substantially larger isotope mass. The potential of an essentially background-free search for neutrinoless double-β decay will facilitate a larger germanium experiment with sensitivity levels that will bring us closer to clarifying whether neutrinos are their own antiparticles.

Background-free search for neutrinoless double-β decay of 76Ge with GERDA

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; di Marco, N.; di Vacri, A.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Fedorova, O.; Freund, K.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Walter, M.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.; GERDA Collaboration

2017-04-01

Many extensions of the Standard Model of particle physics explain the dominance of matter over antimatter in our Universe by neutrinos being their own antiparticles. This would imply the existence of neutrinoless double-β decay, which is an extremely rare lepton-number-violating radioactive decay process whose detection requires the utmost background suppression. Among the programmes that aim to detect this decay, the GERDA Collaboration is searching for neutrinoless double-β decay of 76Ge by operating bare detectors, made of germanium with an enriched 76Ge fraction, in liquid argon. After having completed Phase I of data taking, we have recently launched Phase II. Here we report that in GERDA Phase II we have achieved a background level of approximately 10-3 counts keV-1 kg-1 yr-1. This implies that the experiment is background-free, even when increasing the exposure up to design level. This is achieved by use of an active veto system, superior germanium detector energy resolution and improved background recognition of our new detectors. No signal of neutrinoless double-β decay was found when Phase I and Phase II data were combined, and we deduce a lower-limit half-life of 5.3 × 1025 years at the 90 per cent confidence level. Our half-life sensitivity of 4.0 × 1025 years is competitive with the best experiments that use a substantially larger isotope mass. The potential of an essentially background-free search for neutrinoless double-β decay will facilitate a larger germanium experiment with sensitivity levels that will bring us closer to clarifying whether neutrinos are their own antiparticles.

Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

NASA Astrophysics Data System (ADS)

Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

1998-05-01

Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

Safety, Tolerability, and Immunogenicity of the Novel Antituberculous Vaccine RUTI: Randomized, Placebo-Controlled Phase II Clinical Trial in Patients with Latent Tuberculosis Infection

PubMed Central

Nell, Andre S.; D’lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

Objectives To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Methods and Findings Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV−) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/−): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV− status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. Conclusion This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. Trial Registration ClinicalTrials.gov NCT01136161 PMID:24586912

Environment and Health in Children Day Care Centres (ENVIRH) - Study rationale and protocol.

PubMed

Araújo-Martins, J; Carreiro Martins, P; Viegas, J; Aelenei, D; Cano, M M; Teixeira, J P; Paixão, P; Papoila, A L; Leiria-Pinto, P; Pedro, C; Rosado-Pinto, J; Annesi-Maesano, I; Neuparth, N

2014-01-01

Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children's respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children's health. A building ventilation model will also be developed. This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

PubMed Central

Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

2016-01-01

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. PMID:27992479

External Payload Carrier (XPC) A Suborbital Research Platform

NASA Technical Reports Server (NTRS)

Schallhorn, Paul; Tatro, Chuck; Kutter, Bernard; Szatkowski, Gerald; Stopnitzky, Ben; Bulk, Tim

2011-01-01

This slide presentation details the concept of an External Payload Carrier (XPC), that can fly on ann unused Solid Rocket Booster (SRB) location on the Atlas V rocket to suborbital environment. The XPC can be used anytime there is sufficient excess lift capability available. The dimensions and possible uses of the XPC are reviewed. The completed Phase 1 study reviewed 57 variations, and arrived at three viable configurations, identified design baselines, subsystems and preliminary testing requirements. Phase II effort is planned to produce the preliminary design (i.e., PDR level), Systems Requirements Document (SRD), identify flight candidates, develop schedule and funding profiles, and identify the risk-reduction activities.

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer.

PubMed

Moreno, Lucas; Casanova, Michela; Chisholm, Julia C; Berlanga, Pablo; Chastagner, Pascal B; Baruchel, Sylvain; Amoroso, Loredana; Melcón, Soledad Gallego; Gerber, Nicolas U; Bisogno, Gianni; Fagioli, Franca; Geoerger, Birgit; Glade Bender, Julia L; Aerts, Isabelle; Bergeron, Christophe; Hingorani, Pooja; Elias, Ileana; Simcock, Mathew; Ferrara, Stefano; Le Bruchec, Yvan; Slepetis, Ruta; Chen, Nianhang; Vassal, Gilles

2018-06-21

nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported. Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m 2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m 2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1-2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST. nab-Paclitaxel 240 mg/m 2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. CLINICALTRIALS.GOV: NCT01962103. 2013-000144-26. Copyright © 2018 Elsevier Ltd. All rights reserved.

Controlling Motion Sickness and Spatial Disorientation and Enhancing Vestibular Rehabilitation with a User-Worn See-Through Display

PubMed Central

Krueger, Wesley W.O.

2010-01-01

Objectives/Hypotheses An eyewear mounted visual display (“User-worn see-through display”) projecting an artificial horizon aligned with the user's head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed. Study Design Both phase I and phase II were prospective studies funded by the NIH. The phase II study used repeated measures for motion intolerant subjects and a randomized control group (display device/no display device) pre-post test design for patients in vestibular rehabilitation. Methods Following technology and display device development, 75 patients were evaluated by test and rating scales in the phase II study; 25 subjects with motion intolerance used the technology in the display device in provocative environments and completed subjective rating scales while 50 patients were evaluated before and after vestibular rehabilitation (25 using the display device and 25 in a control group) using established test measures. Results All patients with motion intolerance rated the technology as helpful for nine symptoms assessed, and 96% rated the display device as simple and easy to use. Duration of symptoms significantly decreased with use of the technology displayed. In patients undergoing vestibular rehabilitation, there were no significant differences in amount of change from pre- to post-therapy on objective balance tests between display device users and controls. However, those using the technology required significantly fewer rehabilitation sessions to achieve those outcomes than the control group. Conclusions A user-worn see-through display, utilizing a visual fixation target coupled with a stable artificial horizon and aligned with user movement, has demonstrated substantial benefit for individuals susceptible to motion intolerance and spatial disorientation and those undergoing vestibular rehabilitation. The technology developed has applications in any environment where motion sensitivity affects human performance. PMID:21181963

Enhanced Night Visibility Series, Volume XII : Overview of Phase II and Development of Phase III Experimental Plan

DOT National Transportation Integrated Search

2005-12-01

This volume provides an overview of the six studies that compose Phase II of the Enhanced Night Visibility project and the experimental plan for its third and final portion, Phase III. The Phase II studies evaluated up to 12 vision enhancement system...

Impact of Environmental Issues on the High-Speed Civil Transport

NASA Technical Reports Server (NTRS)

Whitehead, Allen H., Jr.

1998-01-01

This paper provides an overview of the impact of environmental issues on the design and operation of the proposed High-Speed Civil Transport (HSCT). This proposal for a new generation commercial supersonic transport is being pursued by NASA and its US industry partners in the NASA High-Speed Research (HSR) Program. A second related paper describes the overall HSR Program, including a history of supersonic transport development that led to the present program, and a brief outline of the structure of the two-phase program and its management structure. The specific objectives are to address the four major barrier environmental issues and show their impact on the design of the airplane and potentially, its mode of operation. A brief historical perspective shows how HSR Phase I addressed these environmental topics and, with the successful completion of that program, led to the successful advocacy for the Phase II effort that followed. The Phase II program elements were discussed in the earlier paper and addressed technology programs to enhance the economic viability of the HSCT. Since many of the regulations that may effect the certification and operation of the HSCT are either not in place or well documented, a brief treatise is provided to address the status of the rules and the potential impact on the viability of the HSCT.

GAD-treatment of children and adolescents with recent-onset type 1 diabetes preserves residual insulin secretion after 30 months.

PubMed

Ludvigsson, Johnny; Chéramy, Mikael; Axelsson, Stina; Pihl, Mikael; Akerman, Linda; Casas, Rosaura

2014-07-01

This study aimed to analyse data from two different studies (phase II and phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD65 (GAD-alum) at 30 months after administration to children and adolescents with type 1 diabetes. The phase II trial was a double-blind, randomised placebo-controlled study, including 70 children and adolescents who were followed for 30  months. Participants received a subcutaneous injection of either 20 µg of GAD-alum or placebo at baseline and 1 month later. During a subsequent larger European phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD-alum and/or placebo at baseline, 1, 3 and 9  months. The phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow-up, and 45 patients completed the trial at 30 months. Both studies included GAD65 auto-antibodies-positive patients with fasting C-peptide ≥ 0.10 nmol/l. We have now combined the results of these two trials. There were no treatment related adverse events. In patients treated with 2 GAD-alum doses, stimulated C-peptide area under the curve had decreased significantly less (9  m: p  <  0.037; 15 m: p  <  0.032; 21 m: p  <  0.003 and 30  m: p <  0.004), and a larger proportion of these patients were also able to achieve a peak stimulated C-peptide > 0.2  nmol/L (p  <  0.05), as compared with placebo. Treatment with two doses of GAD-alum in children and adolescents with recent-onset type 1 diabetes shows no adverse events and preserves residual insulin secretion. Copyright © 2013 John Wiley & Sons, Ltd.

Reactive sputter deposition of metal oxide nanolaminates

NASA Astrophysics Data System (ADS)

Rubin Aita, Carolyn

2008-07-01

We discuss the reactive sputter deposition of metal oxide nanolaminates on unheated substrates using four archetypical examples: ZrO2 Al2O3, HfO2 Al2O3, ZrO2 Y2O3, and ZrO2 TiO2. The pseudobinary bulk phase diagrams corresponding to these nanolaminates represent three types of interfaces. I. Complete immiscibility (ZrO2 Al2O3 and HfO2 Al2O3). II. Complete miscibility (ZrO2 Y2O3). III. Limited miscibility without a common end-member lattice (ZrO2 TiO2). We found that, although reactive sputter deposition is a far-from-equilibrium process, thermodynamic considerations strongly influence both phase formation within layers and at interfaces. We show that pseudobinary phase diagrams can be used to predict interfacial cation mixing in the nanolaminates. However, size effects must be considered to predict specific structures. In the absence of pseudoepitaxy, size effects play a significant role in determining the nanocrystalline phases that form within a layer (e.g. tetragonal ZrO2, tetragonal HfO2, and orthorhombic HfO2) and at interfaces (e.g. monoclinic (Zr,Ti)O2). These phases are not bulk standard temperature and pressure phases. Their formation is understood in terms of self-assembly into the lowest energy structure in individual critical nuclei.

Overview of Progress on the LANSCE Accelerator and Target Facilities Improvement Program

NASA Astrophysics Data System (ADS)

Macek, R. J.; Brun, T.; Donahue, J. B.; Fitzgerald, D. H.

1997-05-01

Three projects to improve the performance of the accelerator and target facilities for the Los Alamos Neutron Science Center have been initiated since 1994. The LANSCE Reliability Improvement Project was separated into two phases. Phase I, completed in 1995, was targeted at near-term improvements to beam availability that could be completed in a year. Phase II, now underway, consists of two projects: 1) converting the beam injection into the Proton Storage Ring (PSR) from the present two-step process H^- to H^0 to H^+) to direct injection of H^- beam in one step (H^- to H^+), and 2) an upgrade of the spallation neutron production target which will reduce the target change-out time from about a year to about three weeks. The third project, the SPSS Enhancement Project, is aimed at increasing the PSR output beam current from the present 70 μA at 20 Hz to 200 μA at 30 Hz, plus implementing seven new neutron scattering instruments. Objectives, plans, results and progress to date will be summarized.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

An Investigation of the Physical Properties of Erupting Solar Prominences, Phase II

DTIC Science & Technology

2014-12-30

and in two orthogonal states of polarization. It performs full-Stokes spectro- polarimetry , using Hanlé effect polarization measurements to infer the...is slow relative to the turbulence timescale for atmosphere seeing, and the ESF does not have a seeing-correction system, dual-beam polarimetry is...beam polarimetry in removing seeing-induced polarization cross- talk is completely lost. This is because there is no guarantee the slit will sample the

Investigation of Tidal Power, Cobscook Bay, Maine. Environmental Appendix.

DTIC Science & Technology

1980-08-01

Peromyscus leucopus Clethrionomys gapperi Microtus pennsylvanicus Ondatra zibethica Synaptomys cooperi Rattus norvegicua Mus musculus Zapus...hanks of si i oanis so I. ii.il it w i I I ant hi« necessary f<> reset , piles from time to t i r.w ilut" to bank...power. Since tidal power varies with the tides, tidal power is often completely out of phase with normal demand patterns. The surface area of the Bay

Study of the Effect of the Talent Search Program on Secondary and Postsecondary Outcomes in Florida, Indiana and Texas. Final Report from Phase II of the National Evaluation

ERIC Educational Resources Information Center

Constantine, Jill M.; Seftor, Neil S.; Martin, Emily Sama; Silva, Tim; Myers, David

2006-01-01

Low-income students and students whose parents have not attended college typically are less likely than middle- and upper-income students to complete high school and attend college, and are thus less likely to reap the benefits of attending college. Lack of information, resources, and exposure to others who have navigated the college process may…

Center for Dielectric Studies at the Pennsylvania State University,

DTIC Science & Technology

1983-05-01

microstructure. The permittivity shows a weak peak near 100K which also has clear relaxation character and closely duplicates the behavior of higA purity...departures from the expected Curie-Weiss made by Demurov and Venevtsev.1 both hysteresis loops in P(E) behavior . Clearly. from the frequency response and...dielectric measurements, an powderl had second phase KzTa.O,,; powder II was completely anomalous behavior was observed by inelastic neutron scattering

Membrane Transport Phenomena (MTP)

NASA Technical Reports Server (NTRS)

Mason, Larry W.

1997-01-01

The activities during the fourth semi-annual period of the MTP project have involved the completion of the Science Concept Review (SCR) presentation and peer review, continuation of analyses for the mass transfer coefficients measured from MTA experiment data, and development of the second generation (MTP-II) instrument. The SCR panel members were generated several recommendations for the MTP project recommendations are : Table 1 Summary of Primary SCR Panel Recommendations (1) Continue and refine development of mass transfer coefficient analyses (2) Refine and upgrade analytical modeling associated with the MTP experiment. (3) Increase resolution of measurements in proximity of the membrane interface. (4) Shift emphasis to measurement of coupled transport effects (i.e., development of MTP phase II experiment concept).

Change of motion and localization of cholesterol molecule during L(alpha)-H(II) transition.

PubMed Central

Hayakawa, E; Naganuma, M; Mukasa, K; Shimozawa, T; Araiso, T

1998-01-01

Formation of the inverted hexagonal (H(II)) phase from the lamellar (L(alpha)) phase of bovine brain-extracted phosphatidylcholine (BBPC) and phosphatidylethanolamine (BBPE) was investigated using 31P-NMR with or without cholesterol. When the ratio of BBPC to BBPE was 1:1, the H(II) formation was observed in the presence of 33 mol% cholesterol (i.e., BBPC:BBPE:cholesterol = 1:1:1) at 47 degrees C. The fraction of the H(II) phase in the BBPC/BBPE/cholesterol system could be controlled by the addition of dioleoylglycerol. The change of molecular motion of cholesterol affected by the H(II) formation was measured at various ratios of the L(alpha) to H(II) phase with the time-resolved fluorescence depolarization method, using dehydroergosterol as a fluorescent probe. It is observed that the motion of cholesterol became vigorous in the mixture state of the L(alpha) and the H(II) phases compared to that in the L(alpha) or the H(II) phase only. These facts show that cholesterol has the strong ability to induce the H(II) phase, probably by special molecular motion, which includes change of its location from the headgroup area to the acyl-chain area. PMID:9533700

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

NASA Technical Reports Server (NTRS)

Voracek, David

2007-01-01

A viewgraph presentation of flight tests performed on the F/A active aeroelastic wing airplane is shown. The topics include: 1) F/A-18 AAW Airplane; 2) F/A-18 AAW Control Surfaces; 3) Flight Test Background; 4) Roll Control Effectiveness Regions; 5) AAW Design Test Points; 6) AAW Phase I Test Maneuvers; 7) OBES Pitch Doublets; 8) OBES Roll Doublets; 9) AAW Aileron Flexibility; 10) Phase I - Lessons Learned; 11) Control Law Development and Verification & Validation Testing; 12) AAW Phase II RFCS Envelopes; 13) AAW 1-g Phase II Flight Test; 14) Region I - Subsonic 1-g Rolls; 15) Region I - Subsonic 1-g 360 Roll; 16) Region II - Supersonic 1-g Rolls; 17) Region II - Supersonic 1-g 360 Roll; 18) Region III - Subsonic 1-g Rolls; 19) Roll Axis HOS/LOS Comparison Region II - Supersonic (open-loop); 20) Roll Axis HOS/LOS Comparison Region II - Supersonic (closed-loop); 21) AAW Phase II Elevated-g Flight Test; 22) Region I - Subsonic 4-g RPO; and 23) Phase II - Lessons Learned

A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations.

PubMed

Fiedler, Walter; Kayser, Sabine; Kebenko, Maxim; Janning, Melanie; Krauter, Jürgen; Schittenhelm, Marcus; Götze, Katharina; Weber, Daniela; Göhring, Gudrun; Teleanu, Veronica; Thol, Felicitas; Heuser, Michael; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F

2015-06-01

Acute myeloid leukaemia (AML) with FLT3 mutation has a dismal prognosis in elderly patients. Treatment with a combination of FLT3 inhibitors and standard chemotherapy has not been extensively studied. Therefore, we instigated a phase I/II clinical trial of chemotherapy with cytosine arabinoside (Ara-C)/daunorubicin induction (7+3) followed by three cycles of intermediate-dose Ara-C consolidation in 22 AML patients with activating FLT3 mutations. Sunitinib was added at predefined dose levels and as maintenance therapy for 2 years. At dose level 1, sunitinib 25 mg daily continuously from day 1 onwards resulted in two cases with dose-limiting toxicity (DLT), prolonged haemotoxicity and hand-foot syndrome. At dose level -1, sunitinib 25 mg was restricted to days 1-7 of each chemotherapy cycle. One DLT was observed in six evaluable patients. Six additional patients were treated in an extension phase. Thirteen of 22 patients (59%; 8/14 with FLT3-internal tandem duplication and 5/8 with FLT3-tyrosine kinase domain) achieved a complete remission/complete remission with incomplete blood count recovery. For the 17 patients included at the lower dose level, median overall, relapse-free and event-free survival were 1·6, 1·0 and 0·4 years, respectively. Four out of five analysed patients with relapse during maintenance therapy lost their initial FLT3 mutation, suggesting outgrowth of FLT3 wild-type subclones. © 2015 John Wiley & Sons Ltd.

Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.

PubMed

Richardson, Paul G; Soiffer, Robert J; Antin, Joseph H; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L; Steinbach, Gideon; Murray, Karen F; Vogelsang, Georgia B; Chen, Allen R; Krishnan, Amrita; Kernan, Nancy A; Avigan, David E; Spitzer, Thomas R; Shulman, Howard M; Di Salvo, Donald N; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L J; Iacobelli, Massimo; McDonald, George B; Guinan, Eva C

2010-07-01

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

Installation Restoration Program. Phase II--Confirmation/Quantification. Stage 1.

DTIC Science & Technology

1985-03-01

four phases. Phase I, Initial Assessment/ Records Search, is designed to identify possible hazardous waste contami- nated sites and potential...7 71 -. - - IL’ -, 1% 33 AihlIII Is 33 n~iL t iiC UII! ii CL C LU 1-3, Phase II, Confirmation and Quantification, is designed to confirm the...additional monitoring data upon which design of mitigative actions are based. In Phase III, Technology Base Development, appropriate technology is selected and

Installation Restoration Program. Phase II: Stage 1 Problem Confirmation Study, Duluth International Airport, Duluth, Minnesota.

DTIC Science & Technology

1984-10-01

8 iii "i t-. Table of Contents (cont.) Section Title Page -APPENDIX A Acronyms, Definitions, Nomenclature and Units of Measure B Scope of Work, Task...Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective Action Only...Problem Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective

Signal transduction in a covalent post-assembly modification cascade

NASA Astrophysics Data System (ADS)

Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

2017-12-01

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

A phase II study of 5-fluorouracil, leucovorin, adriamycin, and cisplatin (FLAP) for metastatic gastric and gastroesophageal junction adenocarcinoma. A Penn Cancer Clinical Trial Group and Roswell Park Cancer Institute Community Oncology Research Program Trial.

PubMed

Vaughn, D J; Meropol, N J; Holroyde, C; Mintzer, D; Nuamah, I; Armstead, B; Douglass, H O; Haller, D G

1997-06-01

A Phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy (FLAP) in patients with previously untreated advanced gastric and gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients were enrolled to received FLAP in this multi-institutional trial. Response, toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated objective responses, with two complete responses (5%) and 13 partial responses (31%). The median time to disease progression was 17 weeks, and the overall survival duration was 30 weeks. Myelosuppression was significant, requiring dose modifications, but there were no treatment-related deaths. FLAP is an active regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We are presently using this regimen in the neoadjuvant setting in patients with gastric and GE junction cancers.

Status and Prospects for the EXO-200 and nEXO Experiments

NASA Astrophysics Data System (ADS)

Yang, Liang; ">EXO-200, A phase II study of sorafenib (BAY 43–9006) in recurrent diffuse large B cell lymphoma: an eastern cooperative oncology group study (E1404)

PubMed Central

2013-01-01

Patients with diffuse large B cell lymphoma (DLBCL) who are not candidates for or recur after autologous stem cell transplant have a poor overall prognosis. We conducted a phase II study of sorafenib (formerly BAY 43–9006) in the treatment of relapsed DLBCL. Fourteen patients were enrolled and assessed for response. Median number of cycles administered was 3 (range, 1–12). Common grade 3 toxicities included fatigue (29%), rash/desquamation (21%) and diarrhea (14%). One complete response (CR) was observed (the 14th patient enrolled). Response rate was 7% (90% CI, 0.4 – 30%). Duration of response was 6 months. Median progression-free survival (PFS) was 2 months (90% CI, 1 – 5 months). Median overall survival (OS) was 9 months (90% CI, 5 – 16 months). Although sorafenib has demonstrated activity in solid malignancies it demonstrated low single agent activity in treatment of DLBCL. PMID:23829878

A phase II study of bortezomib in patients with MALT lymphoma

PubMed Central

Troch, Marlene; Jonak, Constanze; Müllauer, Leonhard; Püspök, Andreas; Formanek, Michael; Hauff, Wolfgang; Zielinski, Christoph C.; Chott, Andreas; Raderer, Markus

2009-01-01

We have performed a phase II study to evaluate bortezomib in patients with MALT-lymphoma. Sixteen patients entered the trial, 4 had gastric MALT-lymphoma, 7 of the ocular adnexa, one of the colon, and 2 of the parotid, and one patient each the lung and the breast. Bortezomib was given at 1.5 mg/m2 days 1, 4, 8 and 11; repeated every 21 days. The overall response rate was 80% (13/16); 7 patients achieved complete remission (43%), 6 partial response (37%) and 3 stable disease. After a median follow-up of 23 months (range; 8–26), all patients are alive and 4 have relapsed. Fifteen patients required dose reductions due to either neuropathy (7 patients) or diarrhea (8 patients). Bortezomib appears to be active in patients with MALT-lymphoma. However, an unexpectedly high rate of toxicities was seen, warranting assessment of combination schedules with bortezomib at a lower dose than given in our study (ClinicalTrials.govIdentifier: NCT 00373906). PMID:19336742

Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial

PubMed Central

Martín-Martorell, P; Roselló, S; Rodríguez-Braun, E; Chirivella, I; Bosch, A; Cervantes, A

2008-01-01

This is a phase II institutional exploratory trial of biweekly irinotecan and cetuximab administration regimen in metastatic colorectal cancer patients progressing to at least one previous chemotherapy line. A total of 40 patients were treated between November 2005 and November 2007 with irinotecan 180 mg m−2 and cetuximab 500 mg m−2 q2w (every 2 weeks), in every 21-day cycles, until unacceptable toxicity or progressive disease. An overall response rate of 22.5% was obtained (two complete and seven partial responses). The disease control rate was 60%. The time to progression was 3.4 months and the overall survival was 8 months. The toxicity compared very favourably to weekly cetuximab combination schedules. Grade 3/4 adverse effects were observed in 12 patients. Overall, our results turn up very similar both in terms of toxicity and efficacy to those obtained by weekly and biweekly administration regimens. PMID:18665167

Observing the determinants of the psychotherapeutic process in depressive disorders. A clinical case study within a psychodynamic approach.

PubMed

Oasi, Osmano

2015-01-01

This paper focuses on the relationship between depressive disorders, personality configurations, and mental functioning. A one-year treatment of a young man with the diagnosis of Depression is presented: the clinical and empirical points of view are described in depth through an assessment at the beginning and at one year after of an oriented psychodynamic psychotherapy. SCID I and II and HAMRS were administered to the patient in assessment phase. In the same phase he filled in BDI-II, and DEQ; the psychotherapist completed SWAP-200. These clinician instruments were used again after 1 year of the treatment. The PDM point of view is also presented. All sessions are audiotaped: 12 verbatim transcripts were coded with the Defense Mechanisms Rating Scale and CCRT. The results show a decrease in depressive symptoms, a change in some personality configurations, but a substantial invariance of the introjective profile, and a modification in mental functioning.

Phase II trial of cisplatin in advanced or recurrent cancer of the vagina: a Gynecologic Oncology Group Study.

PubMed

Thigpen, J T; Blessing, J A; Homesley, H D; Berek, J S; Creasman, W T

1986-01-01

Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.

Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer

PubMed Central

Mellado, B; Font, A; Alcaraz, A; Aparicio, L A; Veiga, F J G; Areal, J; Gallardo, E; Hannaoui, N; Lorenzo, J R M; Sousa, A; Fernandez, P L; Gascon, P

2009-01-01

Background: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. Methods: Patients with T1c–T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml−1 and/or Gleason score ⩾7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m−2 on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). Results: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was ⩾7 (4+3) in 44 (77%) patients and PSA >20 ng ml−1 in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. Conclusion: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated. PMID:19755998

Surrogate endpoints in randomized cardiovascular clinical trials.

PubMed

Domanski, Michael; Pocock, Stuart; Bernaud, Corine; Borer, Jeffrey; Geller, Nancy; Revkin, James; Zannad, Faiez

2011-08-01

Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Advanced photoinjector experiment photogun commissioning results

NASA Astrophysics Data System (ADS)

Sannibale, F.; Filippetto, D.; Papadopoulos, C. F.; Staples, J.; Wells, R.; Bailey, B.; Baptiste, K.; Corlett, J.; Cork, C.; De Santis, S.; Dimaggio, S.; Doolittle, L.; Doyle, J.; Feng, J.; Garcia Quintas, D.; Huang, G.; Huang, H.; Kramasz, T.; Kwiatkowski, S.; Lellinger, R.; Moroz, V.; Norum, W. E.; Padmore, H.; Pappas, C.; Portmann, G.; Vecchione, T.; Vinco, M.; Zolotorev, M.; Zucca, F.

2012-10-01

The Advanced Photoinjector Experiment (APEX) at the Lawrence Berkeley National Laboratory is dedicated to the development of a high-brightness high-repetition rate (MHz-class) electron injector for x-ray free-electron laser (FEL) and other applications where high repetition rates and high brightness are simultaneously required. The injector is based on a new concept rf gun utilizing a normal-conducting (NC) cavity resonating in the VHF band at 186 MHz, and operating in continuous wave (cw) mode in conjunction with high quantum efficiency photocathodes capable of delivering the required charge at MHz repetition rates with available laser technology. The APEX activities are staged in three phases. In phase 0, the NC cw gun is built and tested to demonstrate the major milestones to validate the gun design and performance. Also, starting in phase 0 and continuing in phase I, different photocathodes are tested at the gun energy and at full repetition rate for validating candidate materials to operate in a high-repetition rate FEL. In phase II, a room-temperature pulsed linac is added for accelerating the beam at several tens of MeV to reduce space charge effects and allow the measurement of the brightness of the beam from the gun when integrated in an injector scheme. The installation of the phase 0 beam line and the commissioning of the VHF gun are completed, phase I components are under fabrication, and initial design and specification of components and layout for phase II are under way. This paper presents the phase 0 commissioning results with emphasis on the experimental milestones that have successfully demonstrated the APEX gun capability of operating at the required performance.

Oral Sulforaphane increases Phase II antioxidant enzymes in the human upper airway

PubMed Central

Riedl, Marc A.; Saxon, Andrew; Diaz-Sanchez, David

2009-01-01

Background Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. Objective We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Methods Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. Results All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 grams broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts. Conclusion Oral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress. Clinical Implications This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease. Capsule Summary A placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells. PMID:19028145

Intracellular angiotensin II directly induces in vitro transcription of TGF-β1, MCP-1 and NHE-3 mRNAs in isolated rat renal cortical nuclei via activation of nuclear AT1 receptors

PubMed Central

Li, Xiao C.; Zhuo, Jia L.

2008-01-01

The present study tested the hypothesis that intracellular angiotensin II (Ang II) directly induces transcriptional effects by stimulating AT1 receptors in the nucleus of rat renal cortical cells. Intact nuclei were freshly isolated from the rat renal cortex and transcriptional responses to Ang II were studied using in vitro RNA transcription assays and semi-quantitative RT-PCR. High power phase contrast micrographs showed that isolated nuclei were encircled by an intact nuclear envelop, stained strongly by the DNA marker DAPI, but not by the membrane or endosomal markers. FITC-labeled Ang II and [125I]-Val5-Ang II binding confirmed the presence of Ang II receptors in the nuclei with a predominance of AT1 receptors. RT-PCR showed that AT1a mRNA expression was 3-fold greater than AT1b receptor mRNAs in these nuclei. In freshly isolated nuclei, Ang II increased in vitro [α-32P]CTP incorporation in a concentration manner, and the effect was confirmed by autoradiography and RNA electrophoresis. Ang II markedly increased in vitro transcription of mRNAs for transforming growth factor-β1 by 143% (p < 0.01), macrophage chemoattractant protein-1 by 89% (p < 0.01), and the sodium and hydrogen exchanger-3 by 110% (p < 0.01). These transcriptional effects of Ang II on the nuclei were completely blocked by the AT1 receptor antagonist losartan (p < 0.01). By contrast, Ang II had no effects on transcription of angiotensinogne and GAPDH mRNAs. Since these transcriptional effects of Ang II in isolated nuclei were induced by Ang II in the absence of cell surface receptor-mediated signaling and completely blocked by losartan, we concluded that Ang II may directly stimulate nuclear AT1a receptors to induce transcriptional responses that are associated with tubular epithelial sodium transport, cellular growth and hypertrophy, and proinflammatory cytokines. PMID:18256274

Differential repression of arylsulphatase synthesis in Aspergillus oryzae.

PubMed

Burns, G R; Wynn, C H

1977-09-15

1. The activities of the three arylsulphatases (arylsulphate sulphohydrolase, EC 3.1.6.1) of Aspergillus oryzae produced under a variety of repressing and non-repressing conditions were determined. 2. These enzymes exhibit different sensitivities to repression by inorganic sulphate. 3. Arylsulphatase I, but not arylsulphatases II and III, exhibits a transient de-repression in the early growth phase in sulphate media. 4. When the fungus is cultured in repressing media and subsequently transferred to non-repressing media, the synthesis of the three enzymes is non-co-ordinate. 5. Growth of the fungus in media containing choline O-sulphate or tyrosine O-sulphate as the sole source of sulphur results in complete de-repression of arylsulphatase I, But the synthesis of arylsulphatases II and III is essentially fully repressed. 6. The marked similarities between the repression characteristics of arylsulphatases II and III, contrasted with those of arylsulphatase I, indicate that the genetic locus of arylsulphatase I is distinct from that of arylsulphatases II and III, suggesting that there are distinct physiological roles for the enzyme.

Applied Meteorology Unit (AMU) Quarterly Report - Fourth Quarter FY-10

NASA Technical Reports Server (NTRS)

Bauman, William; Crawford, Winifred; Barrett, Joe; Watson, Leela; Wheeler, Mark

2010-01-01

Three AMU tasks were completed in this Quarter, each resulting in a forecast tool now being used in operations and a final report documenting how the work was done. AMU personnel completed the following tasks (1) Phase II of the Peak Wind Tool for General Forecasting task by delivering an improved wind forecasting tool to operations and providing training on its use; (2) a graphical user interface (GUI) she updated with new scripts to complete the ADAS Update and Maintainability task, and delivered the scripts to the Spaceflight Meteorology Group on Johnson Space Center, Texas and National Weather Service in Melbourne, Fla.; and (3) the Verify MesoNAM Performance task after we created and delivered a GUI that forecasters will use to determine the performance of the operational MesoNAM weather model forecast.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willoner, T.; Turlington, R.; Koenig, R.

The U.S. Department of Energy (DOE) (Environmental Management [EM], Office of Packaging and Transportation [EM-45]) Packaging and Certification Program (DOE PCP) has developed a Radio Frequency Identification (RFID) tracking and monitoring system, called ARG-US, for the management of nuclear materials packages during transportation and storage. The performance of the ARG-US RFID equipment and system has been fully tested in two demonstration projects in April 2008 and August 2009. With the strong support of DOE-SR and DOE PCP, a field testing program was completed in Savannah River Site's K-Area Material Storage (KAMS) Facility, an active Category I Plutonium Storage Facility, inmore » 2010. As the next step (Phase II) of continued vault testing for the ARG-US system, the Savannah River Site K Area Material Storage facility has placed the ARG-US RFIDs into the 910B storage vault for operational testing. This latest version (Mark III) of the Argonne RFID system now has the capability to measure radiation dose and dose rate. This paper will report field testing progress of the ARG-US RFID equipment in KAMS, the operability and reliability trend results associated with the applications of the system, and discuss the potential benefits in enhancing safety, security and materials accountability. The purpose of this Phase II K Area test is to verify the accuracy of the radiation monitoring and proper functionality of the ARG-US RFID equipment and system under a realistic environment in the KAMS facility. Deploying the ARG-US RFID system leads to a reduced need for manned surveillance and increased inventory periods by providing real-time access to status and event history traceability, including environmental condition monitoring and radiation monitoring. The successful completion of the testing program will provide field data to support a future development and testing. This will increase Operation efficiency and cost effectiveness for vault operation. As the next step (Phase II) of continued vault testing for the ARG-US system, the Savannah River Site K Area Material Storage facility has placed the ARG-US RFIDs into the 910B storage vault. Deploying the ARG-US RFID system lends to a reduced need for manned surveillance and increased inventory periods by providing real-time access to status and event history traceability, including radiation and environmental monitoring. The successful completion of the testing program will provide field data to support future development and testing.« less

Mechanisms and efficiency of the simultaneous removal of metals and cyanides by using ferrate(VI): crucial roles of nanocrystalline iron(III) oxyhydroxides and metal carbonates.

PubMed

Filip, Jan; Yngard, Ria A; Siskova, Karolina; Marusak, Zdenek; Ettler, Vojtech; Sajdl, Petr; Sharma, Virender K; Zboril, Radek

2011-08-29

The reaction of potassium ferrate(VI), K(2)FeO(4), with weak-acid dissociable cyanides--namely, K(2)[Zn(CN)(4)], K(2)[Cd(CN)(4)], K(2)[Ni(CN)(4)], and K(3)[Cu(CN)(4)]--results in the formation of iron(III) oxyhydroxide nanoparticles that differ in size, crystal structure, and surface area. During cyanide oxidation and the simultaneous reduction of iron(VI), zinc(II), copper(II), and cadmium(II), metallic ions are almost completely removed from solution due to their coprecipitation with the iron(III) oxyhydroxides including 2-line ferrihydrite, 7-line ferrihydrite, and/or goethite. Based on the results of XRD, Mössbauer and IR spectroscopies, as well as TEM, X-ray photoelectron emission spectroscopy, and Brunauer-Emmett-Teller measurements, we suggest three scavenging mechanisms for the removal of metals including their incorporation into the ferrihydrite crystal structure, the formation of a separate phase, and their adsorption onto the precipitate surface. Zn and Cu are preferentially and almost completely incorporated into the crystal structure of the iron(III) oxyhydroxides; the formation of the Cd-bearing, X-ray amorphous phase, together with Cd carbonate is the principal mechanism of Cd removal. Interestingly, Ni remains predominantly in solution due to the key role of nickel(II) carbonate, which exhibits a solubility product constant several orders of magnitude higher than the carbonates of the other metals. Traces of Ni, identified in the iron(III) precipitate, are exclusively adsorbed onto the large surface area of nanoparticles. We discuss the relationship between the crystal structure of iron(III) oxyhydroxides and the mechanism of metal removal, as well as the linear relationship observed between the rate constant and the surface area of precipitates. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fierz-complete NJL model study. II. Toward the fixed-point and phase structure of hot and dense two-flavor QCD

NASA Astrophysics Data System (ADS)

Braun, Jens; Leonhardt, Marc; Pospiech, Martin

2018-04-01

Nambu-Jona-Lasinio-type models are often employed as low-energy models for the theory of the strong interaction to analyze its phase structure at finite temperature and quark chemical potential. In particular, at low temperature and large chemical potential, where the application of fully first-principles approaches is currently difficult at best, this class of models still plays a prominent role in guiding our understanding of the dynamics of dense strong-interaction matter. In this work, we consider a Fierz-complete version of the Nambu-Jona-Lasinio model with two massless quark flavors and study its renormalization group flow and fixed-point structure at leading order of the derivative expansion of the effective action. Sum rules for the various four-quark couplings then allow us to monitor the strength of the breaking of the axial UA(1 ) symmetry close to and above the phase boundary. We find that the dynamics in the ten-dimensional Fierz-complete space of four-quark couplings can only be reduced to a one-dimensional space associated with the scalar-pseudoscalar coupling in the strict large-Nc limit. Still, the interacting fixed point associated with this one-dimensional subspace appears to govern the dynamics at small quark chemical potential even beyond the large-Nc limit. At large chemical potential, corrections beyond the large-Nc limit become important, and the dynamics is dominated by diquarks, favoring the formation of a chirally symmetric diquark condensate. In this regime, our study suggests that the phase boundary is shifted to higher temperatures when a Fierz-complete set of four-quark interactions is considered.

Indian Island Mooring Project. Phase II. Completion Report.

DTIC Science & Technology

1984-03-01

32151 B 4299 31859 B 3327 31317 C 4460 31138 C 4266 31414 BUOY #2 394572 1532350 BUOY # 5 393784 1532410 ANCHOR A 4987 32457 ANCHOR A 4044 32990 B 4279...WASHINGTON, D. C. 20374 ;- -:r- -.. :;.\\:.,;:.:- ,- ---- :..-.- -.:-:::.:-:". 5 --.:.-..".- ".".--, .S .’---. : ..-. - ... V-.. .... :.. BLOCK 19 (Con’t...NUMBER 5 . MONITORING ORGANIZATION REPORT # FPO-1-84(2) 6a. NAME OF PERFORM. ORG. 6b. OFFICE SYM 7a. NAME OF MONITORING ORGANIZATION Robert Taggart

Phase 2 SBIR Final Report: An Ultra-Sensitive Optical Biosensor for Flood Safety

DTIC Science & Technology

2002-08-23

can be completed in 2 to 4 hours. Currently accepted tests using commercial test kits based on immunochemical techniques offer results in 22 to 24...tagging is imperfect, leading to a background of non-specific surface and molecular binding limiting the signal. The use of a reporter fluorochrome can ...Waveguide Patterning: Surface flow channels: The rectangular cuvettes (as shown in Section II, Figure 4-3) can be etched using standard techniques. The

Field Assessment of Gopher Tortoise Habitat at Camp Shelby, MS. Phase II: Overstory and Combined Assessments

DTIC Science & Technology

2010-10-17

conditions between active, recently active and randomly selected non-burrow locations at this site. Field surveys were completed in three study areas ...at the installation. On average, burrow sites had a much higher overall occurrence of longleaf pine and significantly lower total basal area as...East Area burrow and non-burrow locations, Camp Shelby, MS 2007 .................. 10 2 Mean basal area per acre for pine and hardwood on T-44, Mars

Estimating the prevalence of borderline personality disorder in psychiatric outpatients using a two-phase procedure.

PubMed

Korzekwa, Marilyn I; Dell, Paul F; Links, Paul S; Thabane, Lehana; Webb, Steven P

2008-01-01

The prevalence of borderline personality disorder (BPD) in outpatient clinics varies greatly (7%-27%) depending on the setting and methodology. We examined the cross-sectional rate of BPD in a general adult outpatient university clinic using a 2-phase procedure: (1) we screened all registered patients with the self-report SCID-II-PQ and (2) we administered the Revised Diagnostic Interview for Borderlines (DIB-R). Sixty-six percent (239/360) of the clinic patients completed the screening: About 72.4% (173/239) (95% confidence interval [CI] = 66.7%, 78.1%) were positive for BPD on the Structured Clinical Interview for DSM-IV Personality Disorders-Patient Questionnaire (SCID-II-PQ), and 22.6% (54/239) (95% CI = 17.3%, 27.9%) were positive for BPD on the DIB-R. Our BPD rate was somewhat higher than recent semistructured interview studies (9%-18%). We believe this is due, in part, to our cross-sectional design and our decision not to exclude acute Axis I disorders. Mostly, however, we believe that our 22.6% incidence of BPD arises from the high morbidity of our sample. Demographic data from 130 of 131 DIB-R completers reveal the following: mean age was 40.2 years, 75.4% were female, most patients were unable to work, and they averaged 3.8 lifetime hospitalizations.

Funding and Strategic Alignment Guidance for Infusing Small Business Innovation Research Technology Into Human Exploration and Operations Mission Directorate Projects at Glenn Research Center for 2015

NASA Technical Reports Server (NTRS)

Nguyen, Hung D.; Steele, Gynelle C.

2016-01-01

This report is intended to help NASA program and project managers incorporate Glenn Research Center Small Business Innovation Research/Small Business Technology Transfer (SBIR)/(STTR) technologies into NASA Human Exploration and Operations Mission Directorate (HEOMD) programs and projects. Other Government and commercial project managers can also find this useful. Introduction Incorporating Small Business Innovation Research (SBIR)-developed technology into NASA projects is important, especially given the Agency's limited resources for technology development. The SBIR program's original intention was for technologies that had completed Phase II to be ready for integration into NASA programs, however, in many cases there is a gap between Technology Readiness Levels (TRLs) 5 and 6 that needs to be closed. After SBIR Phase II projects are completed, the technology is evaluated against various parameters and a TRL rating is assigned. Most programs tend to adopt more mature technologies-at least TRL 6 to reduce the risk to the mission rather than adopt TRLs between 3 and 5 because those technologies are perceived as too risky. The gap between TRLs 5 and 6 is often called the "Valley of Death" (Figure 1), and historically it has been difficult to close because of a lack of funding support from programs. Several papers have already suggested remedies on how to close the gap (Refs. 1 to 4).

[Maternal attachment patterns and personality in post partum depression].

PubMed

Aceti, Franca; Baglioni, Valentina; Ciolli, Paola; De Bei, Francesco; Di Lorenzo, Flavia; Ferracuti, Stefano; Giacchetti, Nicoletta; Marini, Isabella; Meuti, Valentina; Motta, Paola; Roma, Paolo; Zaccagni, Michela; Williams, Riccardo

2012-01-01

This study investigates the prevalence of post partum depression (PPD) in a sample of Roman women, and the role of socio-demographic variables, personality structure and maternal attachment patterns, in order to identify primary and secondary prevention strategies. Data were collected in two phases. During the third trimester of pregnancy, a sample of 453 women completed a socio-demographic data sheet and the Edinburgh Postnatal Depression Scale (EPDS). Among the patients scoring 12 or more at EPDS, 15 entered the second phase of the study and completed SCID-II and Adult Attachment Interview. PPD diagnosis was confirmed by the SCID-I. The study group was compared with a control group. Among the 453 women who were evaluated, 92 (20.3%) scored ≥12 at EPDS, 39 has been enrolled and 15 entered the study. Presence of depressive symptoms was associated with: complications in pregnancy, previous psychiatric disorders, family and marital conflicts. 66.6% of depressed mothers showed more than one diagnosis on Axis II (particularly avoidant/dependent + borderline or histrionic + dependent). The AAI showed a prevalence of insecure (33.3%) and unresolved/disorganized (46.6%) attachment pattern in the clinical group. Our results suggest that psychological factors such as personality structure and attachment patterns are not only involved in post natal affective disorders, but have a key role in the onset and development of PPD.

Prevalence of musculoskeletal and balance disorders in patients enrolled in phase II cardiac rehabilitation.

PubMed

Goel, Kashish; Shen, Jennifer; Wolter, Anne D; Beck, Kathryn M; Leth, Shawn E; Thomas, Randal J; Squires, Ray W; Perez-Terzic, Carmen M

2010-01-01

To determine the prevalence of musculoskeletal, neurological, and balance problems in patients enrolled in early outpatient (phase II) cardiac rehabilitation. Data were assessed retrospectively for 284 consecutive patients who attended the phase II Mayo Clinic Cardiac Rehabilitation program from April 2005 to August 2006. All participants completed a questionnaire that identified the presence of musculoskeletal pain, history of falls, joint replacements, osteoporosis, neurological disorders, and difficulties in performing activities of daily living. Balance assessment was evaluated using the single leg stance and the tandem gait tests. Of the total study population (mean age, 62.1 +/- 12.3 years), 25% reported musculoskeletal pain. A significantly higher prevalence of pain was noted in women than men (37% vs 20%, P = .004) and in those > 65 years than those < or = 65 years (35% vs 17%, P = .001). Back (29%), knee (17%), and hip (8%) pain were the most common symptoms, in order of decreasing frequency. Pain was worse with any activity in 32% of participants while 16% of participants had worsening at night. An abnormality in balance was present in 58% of the study participants and was significantly more common in women (71%) and those > 65 years (83%). Falls or gait instability or both were reported by 11% of participants. Musculoskeletal and balance limitations are common in persons enrolled in early outpatient cardiac rehabilitation, particularly in women and patients > 65 years. Cardiac rehabilitation programs should screen patients for musculoskeletal limitations and incorporate adaptations for treatment strategies of such patients.

Ultrastructural study on the retinal pigment epithelium of human embryos, with special reference to quantitative study on the development of melanin granules.

PubMed

Oguni, M; Tanaka, O; Shinohara, H; Yoshioka, T; Setogawa, T

1991-01-01

The development of the retinal pigment epithelium (RPE) was studied ultrastructurally, using 13 externally normal human embryos, Carnegie stages ranging from 13 to 23 (4-8 week of gestation). Melanosomes in the peripheral and posterior RPE were classified according to Fitzpatrick et al. The melanosome of phase I is formed from the Golgi complex and parcelled off into small vesicles. The vesicle enlarges and elongates to form an oval organelle with membranous structures in it (phase II melanosome). Subsequently, melanin deposits on the membranous structures of the melanosomes (phase III melanosomes), and the completion of this process produces a uniformly electrondense granule without discernible internal structures (phase IV melanosome). Melanosomes of phases III and IV appeared in the RPE at stage 15. As the embryonic stage advanced, the ratio of phase II melanosomes decreased and that of phase IV melanosomes increased. The number of phase III melanosomes reached a peak in the peripheral and posterior RPE at stages 15 and 18, respectively. After stage 17, the increase in melanosomes and intracellular organelles was more prominent in the posterior than in the peripheral RPE. During stages 13 and 15, gap junctions were present not only in the apical but also basal plasma membranes of the RPE. At stage 20, gap junctions in the basal plasma membrane disappeared except for the transitional areas from the RPE to the neural retina (NR). In addition, gap junctions were observed between NR and RPE only in the peripheral region at stage 20. The morphological and quantitative differences in the peripheral and posterior RPE in the embryonic period are discussed.

Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study.

PubMed

Tsukamoto, Shunsuke; Nishizawa, Yuji; Ochiai, Hiroki; Tsukada, Yuichiro; Sasaki, Takeshi; Shida, Dai; Ito, Masaaki; Kanemitsu, Yukihide

2017-12-01

We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

47 CFR 69.727 - Regulatory relief.

Code of Federal Regulations, 2010 CFR

2010-10-01

... customer. (b) Phase II relief. Upon satisfaction of the Phase II triggers specified in §§ 69.709(c) or 69... Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase I... similarly situated customers; and (ii) The price cap LEC excludes all contract tariff offerings from price...

Colliding stellar winds in the eclipsing Wolf-Rayet binary V444 Cygni

NASA Technical Reports Server (NTRS)

Brown, Douglas N.; Shore, Steven N.

1988-01-01

High resolution spectra of V444 Cygni have been obtained using the International Ultraviolet Explorer Satellite. These spectra span both eclipses and include one observation at third quadrature. Together with seven archival spectra, they provide reasonably complete phase coverage for the system. The variations in the P Cygni profiles of the He(II) and N(IV) lines, imply the existence of a low density region in the WR wind. This region occupies a relatively narrow range of orbital phase coinciding with the highest terminal velocities observed in C IV. These data are interpreted to be evidence of an interaction region separating the winds of the O-star and Wolf-Rayet star.

Development of a dome Fresnel lens/gallium arsenide photovoltaic concentrator for space applications

NASA Technical Reports Server (NTRS)

O'Neill, Mark J.; Piszczor, Michael F.

1987-01-01

A novel photovoltaic concentrator system is currently being developed. Phase I of the program, completed in late 1986, produced a conceptual design for the concentrator system, including an array weight and performance estimates based on optical, electrical, and thermal analyses. Phase II of the program, just underway, concerns the fabrication and testing of prototype concentrator panels of the design. The concentrator system uses dome Fresnel lenses for optical concentration; gallium arsenide concentrator cells for power generation; prismatic cell covers to eliminate gridline obscuration losses; a backplane radiator for heat rejection; and a honeycomb structure for the deployable panel assembly. The conceptual design of the system, its anticipated performance, and its estimated weight are reported.

47 CFR 90.769 - Construction and implementation of Phase II nationwide licenses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Use of Frequencies in the 220-222 MHz Band Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.769 Construction and implementation of Phase II nationwide licenses...

The manic phase of Bipolar disorder significantly impairs theory of mind decoding.

PubMed

Hawken, Emily R; Harkness, Kate L; Lazowski, Lauren K; Summers, David; Khoja, Nida; Gregory, James Gardner; Milev, Roumen

2016-05-30

Bipolar disorder is associated with significant deficits in the decoding of others' mental states in comparison to healthy participants. However, differences in theory of mind decoding ability among patients in manic, depressed, and euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to control for non-mentalistic response demands of the Eyes Task. Patients also completed self-report and clinician-rated measures of depression, mania, and anxiety symptoms. Patients in the manic phase were significantly less accurate than those in the depressed and euthymic phases at decoding mental states in the Eyes task, and this effect was strongest for eyes of a positive or neutral valence. Further Eyes task performance was negatively correlated with the symptoms of language/thought disorder, pressured speech, and disorganized thoughts and appearance. These effects held when controlling for accuracy on the Animals task, response times, and relevant demographic and clinical covariates. Results suggest that the state of mania, and particularly psychotic symptoms that may overlap with the schizophrenia spectrum, are most strongly related to social cognitive deficits in bipolar disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of a Comprehensive Heart Disease Knowledge Questionnaire

PubMed Central

Bergman, Hannah E.; Reeve, Bryce B.; Moser, Richard P.; Scholl, Sarah; Klein, William M. P.

2011-01-01

Background Heart disease is the number one killer of both men and women in the United States, yet a comprehensive and evidence-based heart disease knowledge assessment is currently not available. Purpose This paper describes the 2 phase development of a novel heart disease knowledge questionnaire. Methods After review and critique of the existing literature, a questionnaire addressing 5 central domains of heart disease knowledge was constructed. In Phase I, 606 undergraduates completed a 82-item questionnaire. In Phase II, 248 undergraduates completed a revised 74-item questionnaire. In both phases, item clarity and difficulty were evaluated, along with the overall factor structure of the scale. Results Exploratory and confirmatory factor analyses were used to reduce the scale to 30 items with fit statistics, CFI = .82, TLI = .88, and RMSEA = .03. Scores were correlated moderately positively with an existing scale and weakly positively with a measure of health literacy, thereby establishing both convergent and divergent validity. Discussion The finalized 30-item questionnaire is a concise, yet discriminating instrument that reliably measures participants' heart disease knowledge levels. Translation to Health Education Practice Health professionals can use this scale to assess their patients' heart disease knowledge so that they can create a tailored program to help their patients reduce their heart disease risk. PMID:21720571

Unveiling the control of quenched disorder in rare earth nickelates

NASA Astrophysics Data System (ADS)

Das, Sarmistha; Phanindra, V. Eswara; Philip, Sharon S.; Rana, D. S.

2017-10-01

The role of quenched disorder, a key control to obtain novel phases and functionalities, has not yet been determined in the complex phase diagram of RNi O3 (R = rare-earth ion) perovskites. Here we present such a study by investigating (L a0.5E u0.5 ) Ni O3 (LENO) having large R-site cation disorder. We show that in the presence of quenched disorder, (i) the resistivity drops by a few orders of magnitude across the metal-insulator transition (MIT) but the MIT shows only a subtle decrease, (ii) compressive films are completely metallic while largely tensile films are completely insulating sans a MIT, (iii) orthorhombic distortion promotes sharp MIT, and (iv) a Fermi liquid behavior even as high temperature resistivity exceeds the Mott-Ioffe-Regel limit with a bad metallic state. The low-energy terahertz conductivity dynamics obey Drude and Drude-Smith models for compressive and tensile films, respectively. All these features of disordered LENO, which are not typical of prototype ordered NdNi O3 , reveal an extraordinary sensitivity to slight structural perturbations. This study depicts the ease with which a variety of electronic phases can be tuned in disordered nickelates and emphasize the need to incorporate quenched disorder as a key control in the phase diagram of nickelates.

Non-enzymatic U(VI) interactions with biogenic mackinawite

NASA Astrophysics Data System (ADS)

Veeramani, H.; Qafoku, N. P.; Kukkadapu, R. K.; Murayama, M.; Hochella, M. F.

2011-12-01

Reductive immobilization of hexavalent uranium [U(VI)] by stimulation of dissimilatory metal and/or sulfate reducing bacteria (DMRB or DSRB) has been extensively researched as a remediation strategy for subsurface U(VI) contamination. These bacteria derive energy by reducing oxidized metals as terminal electron acceptors, often utilizing organic substrates as electron donors. Thus, when evaluating the potential for in-situ uranium remediation in heterogeneous subsurface media, it is important to understand how the presence of alternative electron acceptors such as Fe(III) and sulfate affect U(VI) remediation and the long term behavior and reactivity of reduced uranium. Iron, an abundant subsurface element, represents a substantial sink for electrons from DMRB, and the reduction of Fe(III) leads to the formation of dissolved Fe(II) or to reactive biogenic Fe(II)- and mixed Fe(II)/Fe(III)- mineral phases. Consequently, abiotic U(VI) reduction by reactive forms of biogenic Fe(II) minerals could be a potentially important process for uranium immobilization. In our study, the DMRB Shewanella putrefaciens CN32 was used to synthesize a biogenic Fe(II)-bearing sulfide mineral: mackinawite, that has been characterized by XRD, SEM, HRTEM and Mössbauer spectroscopy. Batch experiments involving treated biogenic mackinawite and uranium (50:1 molar ratio) were carried out at room temperature under strict anoxic conditions. Following complete removal of uranium from solution, the biogenic mackinawite was analyzed by a suite of analytical techniques including XAS, HRTEM and Mössbauer spectroscopy to determine the speciation of uranium and investigate concomitant Fe(II)-phase transformation. Determining the speciation of uranium is critical to success of a remediation strategy. The present work elucidates non-enzymatic/abiotic molecular scale redox interactions between biogenic mackinawite and uranium.

The emplacement of long lava flows in Mare Imbrium, the Moon

NASA Astrophysics Data System (ADS)

Garry, W. B.

2012-12-01

Lava flow margins are scarce on the lunar surface. The best developed lava flows on the Moon occur in Mare Imbrium where flow margins are traceable nearly their entire flow length. The flow field originates in the southwest part of the basin from a fissure or series of fissures and cones located in the vicinity of Euler crater and erupted in three phases (Phases I, II, III) over a period of 0.5 Billion years (3.0 - 2.5 Ga). The flow field was originally mapped with Apollo and Lunar Orbiter data by Schaber (1973) and shows the flow field extends 200 to 1200 km from the presumed source area and covers an area of 2.0 x 10^5 km^2 with an estimated eruptive volume of 4 x 10^4 km^3. Phase I flows extend 1200 km and have the largest flow volume, but interestingly do not exhibit visible topography and are instead defined by difference in color from the surrounding mare flows. Phases II and III flows have well-defined flow margins (10 - 65 m thick) and channels (0.4 - 2.0 km wide, 40 - 70 m deep), but shorter flow lengths, 600 km and 400 km respectively. Recent missions, including Lunar Reconnaissance Orbiter (LRO), Kaguya (Selene), and Clementine, provide high resolution data sets of these lava flows. Using a combination of data sets including images from LRO Wide-Angle-Camera (WAC)(50-100 m/pixel) and Narrow-Angle-Camera (NAC) (up to 0.5m/pixel), Kaguya Terrain Camera (TC) (10 m/pixel), and topography from LRO Lunar Orbiter Laser Altimeter (LOLA), the morphology has been remapped and topographic measurements of the flow features have been made in an effort to reevaluate the emplacement of the flow field. Morphologic mapping reveals a different flow path for Phase I compared to the original mapping completed by Schaber (1973). The boundaries of the Phase I flow field have been revised based on Moon Mineralogy Mapper color ratio images (Staid et al., 2011). This has implications for the area covered and volume erupted during this stage, as well as, the age of Phase I. Flow features and margins have been identified in the Phase I flow within the LROC WAC mosaic and in Narrow Angle Camera (NAC) images. These areas have a mottled appearance. LOLA profiles over the more prominent flow lobes in Phase I reveal these margins are less 10 m thick. Phase II and III morphology maps are similar to previous flow maps. Phase III lobes near Euler are 10-12 km wide and 20-30 m thick based on measurements of the LOLA 1024ppd Elevation Digital Terrain Model (DTM) in JMoon. One of the longer Phase III lobes varies between 15 to 50 km wide and 25 to 60 m thick, with the thickest section at the distal end of the lobe. The Phase II lobe is 15 to 25 m thick and up to 35 km wide. The eruptive volume of the Mare Imbrium lava flows has been compared to terrestrial flood basalts. The morphology of the lobes in Phase II and III, which includes levees, thick flow fronts, and lobate margins suggests these could be similar to terrestrial aa-style flows. The Phase I flows might be more representative of sheet flows, pahoehoe-style flows, or inflated flows. Morphologic comparisons will be made with terrestrial flows at Askja volcano in Iceland, a potential analog to compare different styles of emplacement for the flows in Mare Imbrium.

The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with erectile dysfunction.

PubMed

Fisher, William A; Rosen, Raymond C; Eardley, Ian; Niederberger, Craig; Nadel, Andrea; Kaufman, Joel; Sand, Michael

2004-09-01

The aim of Phase II of the Men's Attitudes to Life Events and Sexuality (MALES) Study is to explore PDE5 inhibitor treatment seeking among men with erectile dysfunction (ED). Phase II of the MALES study involved 2,912 men, aged 20-75 years, from 8 countries (U.S., U.K., Germany, France, Italy, Spain, Mexico, and Brazil), who reported ED. Participants were recruited from the MALES Phase I sample [1] and via booster methods (e.g., physician referral, street interception), and completed self-report questionnaires concerning the characteristics of their ED, their efforts to seek PDE5 inhibitor treatment for their sexual dysfunction, and attitudinal and referent influences that potentially affect treatment-seeking. Statistical analyses focus on identification of correlates of PDE5 inhibitor treatment seeking. PDE5 inhibitor utilization is strongly associated with ED sufferers' assessment of the severity of their sexual dysfunction, with their belief that medication for ED is dangerous, and with their perceptions of whether physicians, other professionals, and spouses or family members are supportive of their seeking treatment. ED sufferers who evaluate their sexual dysfunction as severe, who believe that medication for ED is not dangerous, and who perceive support for treatment seeking from referent others, are more likely to utilize PDE5 inhibitor treatment. Findings indicate that perceived ED severity, beliefs about ED medication, and referent influences are strongly correlated with utilization of PDE5 inhibitor therapy. These findings aid our understanding of factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy for their sexual dysfunction, and provide a basis for clinical and educational interventions to assist men with ED to seek appropriate treatment.

High-repetition-rate, widely tunable terahertz generation in GaSe pumped by a dual-wavelength KTP-OPO

NASA Astrophysics Data System (ADS)

Yan, Dexian; Xu, Degang; Wang, Yuye; Shi, Wei; Zhong, Kai; Liu, Pengxiang; Yan, Chao; Sheng, Quan; Mei, Jialin; Shi, Jia; Yao, Jianquan

2016-11-01

High-repetition-rate, monochromatic and tunable terahertz (THz) source is demonstrated. We use an orthogonally polarized dual-wavelength intracavity OPO to complete the type-II phase-matched collinear difference-frequency generation in GaSe. A high average-power 2 μm laser with 12 W output power and good beam quality based on an intracavity KTP OPO is experimentally designed. The KTP OPO is intracavity pumped by an acousto-optical Q-switched side-pumped Nd:YAG with the repetition rate of 10 kHz. Two identical KTP crystals were 7 × 8 × 15 mm3 in size, cut at θ = 51.2°, φ = 0°, which were tuned in the x-z plane to achieve type-II phase-matching. The KTP OPO consists of two identical KTP crystals to reduce the walk-off effect and improve the beam overlap area of the output signal and idler waves. The pulse-width of the 2-μm KTP OPO laser is about 11 ns with the linewidth about 0.8 nm. The focused OPO beam is injected into the uncoated GaSe with the length of 8 mm, and the generated THz wave is detected with a 4.2-K Si-bolometer after focusing with a polyethylene lens. The tunable and coherent radiation from 0.2 to 3 THz has been achieved based on the type-II phase-matching DFG when the two pump waves are in the range of 2.1064 - 2.1272 μm and 2.1516 - 2.1304 μm while symmetrically tuning the phase-matching angle of the KTPs. The maximum output THz average power can reach μW-level around 1.48 THz.

What Works in Oklahoma Schools: A Comprehensive Needs Assessment of Oklahoma Schools. Phase II State Report

ERIC Educational Resources Information Center

Marzano Research Laboratory, 2010

2010-01-01

Phase II provides a more detailed examination of classroom variables important to achievement in Oklahoma schools. Where Phase I addressed all nine of the Oklahoma essential elements using survey data, Phase II focuses on what occurs in Oklahoma classrooms primarily using data from principal interviews, classroom observations (on-site), and video…

Safinamide: FCE 26743, NW 1015, PNU 151774, PNU 151774E.

PubMed

2004-01-01

Safinamide [NW 1015, PNU 151774E; FCE 26743] is a potent anticonvulsant and antiparkinsonian compound that is being developed by Newron Pharmaceuticals in Europe. It has been shown to antagonise the calcium and sodium channels, as well as inhibit monoamine oxidase type-B (MAO-B). Phase III trials for the treatment of Parkinson's disease are underway in Germany and Europe, while phase II trials in patients with epilepsy are ongoing in Italy. Newron Pharmaceuticals was founded at the end of 1998 after Pharmacia & Upjohn announced its worldwide restructuring programme. Newron obtained the rights to safinamide, which Pharmacia Corporation (now Pfizer) had been developing as PNU 151774E. Safinamide was originated by Farmitalia-CarloErba in Italy. Newron now owns all intellectual property associated with the drug.A multinational phase II trial for Parkinson's disease in Europe has shown positive results in slowing the progression of the disease; however, due to the placebo-effect seen in this study, a longer (6-month) phase IIb study is planned for the second quarter of 2003. In July 2003, Newron received an IND from the US FDA authorising a phase I trial to confirm that no dietary restrictions are needed in patients while being treated with safinamide. This study is be conducted in 12 healthy volunteers at the University of Vienna, Austria, and will be followed by efficacy studies in Parkinson's disease in the US. Five phase I trials were completed in April 2001 in Switzerland. Safinamide combines sodium and calcium channel modulatory activity with monoamine oxidase B inhibition.

The effect of the menstrual cycle on optic nerve head analysis in healthy women.

PubMed

Akar, Munire Erman; Taskin, Omur; Yucel, Iclal; Akar, Yusuf

2004-12-01

To determine the effect of the menstrual cycle on optic nerve head topographic analysis in normally menstruating, healthy women. The study included single eyes selected randomly from each of 52 healthy women with regular menstrual cycles. All subjects underwent a complete ocular examination. Optic nerve head topographic analyses were performed using a confocal scanning laser ophthalmoscope, the Heidelberg Retinal Tomograph II (HRT II, software version 1.6). The analyses were repeated three times during the menstrual cycle: in the follicular phase (days 7-10 of the cycle), at ovulation, and in the late luteal phase (days 1-3 before menstrual bleeding). Serum oestradiol, progesterone and luteinizing hormone levels were measured at each menstrual phase. Fourteen subjects were excluded from the study. The mean age of the subjects (n = 38) was 25.6 +/- 3.7 years (range 21-34 years). Blood oestradiol levels were significantly lower in the late luteal phase (35.8 pg/ml) (p < 0.0001). The mean disc area of the subjects was 1.94 +/- 0.33 mm(2). The neuroretinal rim area decreased significantly during the luteal phase (p < 0.001). However, the linear cup : disc ratio, cup : disc area ratio and the cup area were significantly higher during the luteal phase (p < 0.001). These observations raise the possibility that sex hormone fluctuations which occur during a normal menstrual cycle in healthy women significantly alter neuroretinal rim area and cup variables of the optic nerve head. These findings should be taken into consideration in the clinical follow-up of young women with glaucoma.

Techniques for the characterization of sub-10-fs optical pulses: a comparison

NASA Astrophysics Data System (ADS)

Gallmann, L.; Sutter, D. H.; Matuschek, N.; Steinmeyer, G.; Keller, U.

Several methods have been proposed for the phase and amplitude characterization of sub-10-fs pulses with nJ energies. An overview of these techniques is presented, with a focus on the comparison of second-harmonic generation frequency-resolved optical gating (SHG-FROG) and spectral phase interferometry for direct electric-field reconstruction (SPIDER). We describe a collinear FROG variant based on type-II phase-matching that completely avoids the geometrical blurring artifact and use both this and SPIDER for the characterization of sub-10-fs Ti:sapphire laser pulses. The results of both methods are compared in an extensive statistical analysis. From this first direct experimental comparison of FROG and SPIDER, guidelines for accurate measurements of sub-10-fs pulses are derived. We point out limitations of both methods for pulses in this ultrashort pulse regime.

Wind tunnel tests of the dynamic characteristics of the fluidic rudder

NASA Technical Reports Server (NTRS)

Belsterling, C. A.

1976-01-01

The fourth phase is given of a continuing program to develop the means to stabilize and control aircraft without moving parts or a separate source of power. Previous phases have demonstrated the feasibility of (1) generating adequate control forces on a standard airfoil, (2) controlling those forces with a fluidic amplifier and (3) cascading non-vented fluidic amplifiers operating on ram air supply pressure. The foremost objectives of the fourth phase covered under Part I of this report were to demonstrate a complete force-control system in a wind tunnel environment and to measure its static and dynamic control characteristics. Secondary objectives, covered under Part II, were to evaluate alternate configurations for lift control. The results demonstrate an overall response time of 150 msec, confirming this technology as a viable means for implementing low-cost reliable flight control systems.

The Heliopause Electrostatic Rapid Transit System (HERTS) Design, Trades, and Analyses Performed in a Two Year NASA Investigation of Electric Sail Propulsion Systems

NASA Technical Reports Server (NTRS)

Wiegmann, Bruce M.

2017-01-01

The Heliopause Electrostatic Rapid Transit System (HERTS) was one of the seven total Phase II NASA Innovative Advanced Concepts (NIAC) that was down-selected in 2015 for continued funding and research. In Phase I our team learned that a spacecraft propelled by an Electric Sail (E-Sail) can travel great astronomical distances, such as to the Heliopause region of the solar system (approx. 100 to 120 AU) in approximately one quarter of the time (10 years) versus the time it took the Voyager spacecraft launched in 1977 (36 years). The completed work within the Phase II NIAC funded effort builds upon the work that was done in the Phase I NIAC and is focused on: 1) Testing of plasma interaction with a charged wire in a MSFC simulated solar environment vacuum test chamber. 2) Development of a Particle-in-Cell (PIC) models that are validated in the plasma testing and used to extrapolate to the E-Sail propulsion system design. 3) Conceptual design of a Technology Demonstration Mission (TDM) spacecraft developed to showcase E-Sail propulsion systems. 4) Down selection of both: a) Materials for a multi km length conductor and, b) Best configuration of the proposed conductor deployment subsystem. This paper will document the findings to date (June, 2017) of the above focused areas.

BG 12: BG 00012, BG 12/Oral Fumarate, FAG-201, second-generation fumarate derivative--Fumapharm/Biogen Idec.

PubMed

2005-01-01

Fumapharm AG has developed a second-generation fumarate (fumaric acid) derivative, BG 12 [BG 00012, FAG-201, BG 12/Oral Fumarate], for the oral treatment of psoriasis. Biogen Idec is currently evaluating the product in clinical trials as an oral treatment for multiple sclerosis (phase II) and psoriasis (phase III) trials.BG 12 has an immunomodulatory mechanism of action. It seems that this product has been developed to reduce the adverse effects associated with a first-generation product containing fumaric acid esters (mixed dimethylfumarate and monoethylfumarate salts), Fumaderm. Fumaderm was approved in Germany in August 1994 and is currently the leading oral systemic therapy for moderate-to-severe psoriasis in Germany. One of the problems associated with Fumaderm capsules has been its gastrointestinal adverse effects (including diarrhoea and nausea). In September 2003, Biogen (now Biogen Idec) licensed exclusive worldwide rights (excluding Germany) from Fumapharm to develop and market BG 12. Biogen plans to collaborate with Fumapharm to accelerate phase III development for psoriasis and the registration programme worldwide. Financial terms of the agreement were not disclosed. Development plans for BG 12 include other autoimmune and inflammatory disorders, such as multiple sclerosis. In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec. Fumapharm completed phase II trials of this second-generation fumarate derivative for psoriasis prior to licensing of the product to Biogen, also with positive results.

Use of defibrotide in the treatment and prevention of veno-occlusive disease.

PubMed

Richardson, Paul; Linden, Erica; Revta, Carolyn; Ho, Vincent

2009-08-01

Hepatic veno-occlusive disease (VOD) is one of the most important complications of high-dose chemotherapy and stem cell transplantation. VOD is a clinical syndrome characterized by jaundice, hepatic enlargement and fluid retention typically seen by day +30 after transplantation. Severe VOD is complicated by multiorgan failure and a high mortality rate approaching 100%. Defibrotide (DF) is a novel agent with both antithrombotic and fibrinolytic properties that has emerged as an effective therapy for severe VOD. In Phase II studies, treatment of severe VOD has resulted in complete responses of 30-60% and survival past day 100 ranging between 32-50%. A Phase III, historically controlled study of DF for treatment of severe VOD has recently been completed and results are awaited with interest. In addition, DF may be effective prophylaxis for VOD in high-risk patients. This review will focus on a summary of the pharmacology of DF and the clinical evidence for its use in VOD.

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

PubMed

Lonardi, S; Sobrero, A; Rosati, G; Di Bartolomeo, M; Ronzoni, M; Aprile, G; Massida, B; Scartozzi, M; Banzi, M; Zampino, M G; Pasini, F; Marchetti, P; Cantore, M; Zaniboni, A; Rimassa, L; Ciuffreda, L; Ferrari, D; Barni, S; Zagonel, V; Maiello, E; Rulli, E; Labianca, R

2016-11-01

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Alabama Coronary Artery Bypass Grafting Project

PubMed Central

Holman, William L.; Sansom, Monique; Kiefe, Catarina I.; Peterson, Eric D.; Hubbard, Steve G.; Delong, James F.; Allman, Richard M.

2004-01-01

Objective/Background: This report describes the first round of results for Phase II of the Alabama CABG Project, a regional quality improvement initiative. Methods: Charts submitted by all hospitals in Alabama performing CABG (ICD-9 codes 36.10–36.20) were reviewed by a Clinical Data Abstraction Center (CDAC) (preintervention 1999–2000; postintervention 2000–2001). Variables that described quality in Phase I were abstracted for Phase II and data describing the new variables of β-blocker use and lipid management were collected. Data samples collected onsite by participating hospitals were used for rapid cycle improvement in Phase II. Results: CDAC data (n = 1927 cases in 1999; n = 2001 cases in 2000) showed that improvements from Phase I in aspirin prescription, internal mammary artery use, and duration of intubation persisted in Phase II. During Phase II, use of β-blockers before, during, or after CABG increased from 65% to 76% of patients (P < 0.05). Appropriate lipid management, an aggregate variable, occurred in 91% of patients before and 91% after the educational intervention. However, there were improvements in 3 of 5 subcategories for lipid management (documenting a lipid disorder [52%–57%], initiating drug therapy [45%–53%], and dietary counseling [74%–91%]; P < 0.05). Conclusions: In Phase II, this statewide process-oriented quality improvement program added two new measures of quality. Achievements of quality improvement from Phase I persisted in Phase II, and improvements were seen in the new variables of lipid management and perioperative use of β-blockers. PMID:14685107

Electric Utility Phase I Acid Rain Compliance Strategies for the Clean Air Act Amendments of 1990

EIA Publications

1994-01-01

The Acid Rain Program is divided into two time periods; Phase I, from 1995 through 1999, and Phase II, starting in 2000. Phase I mostly affects power plants that are the largest sources of SO2 and NOx . Phase II affects virtually all electric power producers, including utilities and nonutilities. This report is a study of the effects of compliance with Phase I regulations on the costs and operations of electric utilities, but does not address any Phase II impacts.

Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease and Multiorgan Failure after Stem Cell Transplantation: A Multicenter, Randomized, Dose-Finding Trial

PubMed Central

Richardson, Paul G.; Soiffer, Robert J.; Antin, Joseph H.; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L.; Steinbach, Gideon; Murray, Karen F.; Vogelsang, Georgia B.; Chen, Allen R.; Krishnan, Amrita; Kernan, Nancy A.; Avigan, David E.; Spitzer, Thomas R.; Shulman, Howard M.; Di Salvo, Donald N.; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L. J.; Iacobelli, Massimo; McDonald, George B.; Guinan, Eva C.

2010-01-01

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for ≥ 14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day + 100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day + 100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD. PMID:20167278

Durability of lightweight concrete : Phase II : wetting and drying tests, Phase III : freezing and thawing tests.

DOT National Transportation Integrated Search

1966-12-01

This report describes a laboratory research program on the durability of lightweight concrete. Two phases of a three phase study are covered by this report, while the remaining phase is still under study. The two phases being reported are Phase II - ...

Ion Conduction Path and Low-Temperature Form:. Argyrodite-Type Superionic Conductors

NASA Astrophysics Data System (ADS)

Onoda, M.; Wada, H.; Sato, A.; Ishii, M.

2007-01-01

The structures of the orthorhombic room-temperature phase of Cu8GeS6 (phase II) and the monoclinic low-temperature phase of Ag7TaS6 (phase II) have been successfully refined based on X-ray diffraction data from 12-fold twinned (Cu8GeS6 II) and 24-fold twinned (Ag7TaS6 II) crystals. Respectively among 6 major and 6 minor twin domains of Cu8GeS6 II, or among 12 major and 12 minor twin domains of Ag7TaS6 II, the argyrodite-type frameworks, GeS6 or TaS6, can be superposed to each other in principle, and only Cu-Cu or Ag-Ag network directions differ. At higher temperature, the crystals were considered to be 2-fold twinned crystals of superionic-conductor phase I with a space group F 43m. On cooling, each domain transforms into 6 domains of orthorhombic Cu8GeS6 II or 12 domains of monoclinic Ag7TaS6 II. Superposed projections along 6 directions of the structure of Cu8GeS6 II and along 12 directions of the structure of Ag7TaS6 II seem to show approximate expressions for Cu-ion and Ag-ion conduction paths in superionic-conductor phases, Cu8GeS6 I and Ag7TaS6I.

Estimates of general combining ability in Hevea breeding at the Rubber Research Institute of Malaysia : I. Phases II and III A.

PubMed

Tan, H

1977-01-01

Estimates of general combining ability of parents for yield and girth obtained separately from seedlings and their corresponding clonal families in Phases II and IIIA of the RRIM breeding programme are compared. A highly significant positive correlation (r = 0.71***) is found between GCA estimates from seedling and clonal families for yield in Phase IIIA, but not in Phase II (r = -0.03(NS)) nor for girth (r= -0.27(NS)) in Phase IIIA. The correlations for Phase II yield and Phase IIIA girth, however, improve when the GCA estimates based on small sample size or reversed rankings are excluded.When the best selections (based on present clonal and seedling information) are compared, all five of the parents top-ranking for yield are common in Phase IIIA but only two parents are common for yield and girth in Phases II and IIIA respectively. However, only one parent for yield in Phase II and two parents for girth in Phase IIIA would, if selected on clonal performance, have been omitted from the top ranking selections made by previous workers using seedling information.These findings, therefore, justify the choice of parents based on GCA estimates for yield obtained from seedling performance. Similar justification cannot be offered for girth, for which analysis is confounded by uninterpretable site and seasonal effects.

The PTSD Practitioner Registry: An Innovative Tracking, Dissemination, and Support Tool for Providers in Military and Nonmilitary settings

DTIC Science & Technology

2017-10-01

the registry as well as pre- test the proposed registry survey. In Phase II, an RCT is being conducted to evaluate the impact of registry...disorders is a compelling priority for clinicians working with active-duty Warriors and Veterans with Post Traumatic Stress Disorder (PTSD). The PTSD...4. 2) Develop and pre- test interview modules (10/14-11/14) 100% complete on 03/15 3) Recruit providers for interview assessments (10/14-03/15)100

Bipolar gas outflow from the nova V458 Vul

NASA Astrophysics Data System (ADS)

Goranskij, V. P.; Barsukova, E. A.; Fatkhullin, T. A.

2010-06-01

Classical nova V458 Vul (N Vul 2007 No.1) was detected as a supersoft X-ray source by the Swift XRT (ATel#1246, #1603). This star is interesting with its spectral class change: features of Fe II class nova completely changed by features of He/N class in the SSS phase (T.N. Tarasova, IBVS No.5807). We performed spectral observations of V458 Vul with the Russian 6-m telescope BTA and spectral camera SCORPIO on 2010 June 9.84 UT.

Tunable PhoXonic Band Gap Materials from Self-Assembly of Block Copolymers and Colloidal Nanocrystals (NBIT Phase II)

DTIC Science & Technology

2013-12-12

their application in sensors and as displays. We found that the thermochromic behavior of a lamellar block copolymer poly(styrene-b-2-vinylpyridine...the solution pH. The findings of this work provide the basis for understanding and controlling the properties of thermochromic block copolymers...by the glassy PS layers . The glassy layers completely constrain the lateral expansion of the P2VP gel block and the dislocation defect network that

Communication-Efficient Arbitration Models for Low-Resolution Data Flow Computing

DTIC Science & Technology

1988-12-01

phase can be formally described as follows: Graph Partitioning Problem NP-complete: (Garey & Johnson) Given graph G = (V, E), weights w (v) for each v e V...Technical Report, MIT/LCS/TR-218, Cambridge, Mass. Agerwala, Tilak, February 1982, "Data Flow Systems", Computer, pp. 10-13. Babb, Robert G ., July 1984...34Parallel Processing with Large-Grain Data Flow Techniques," IEEE Computer 17, 7, pp. 55-61. Babb, Robert G ., II, Lise Storc, and William C. Ragsdale

Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.

PubMed

Gana, Inès; Barrio, Maria; Do, Bernard; Tamarit, Josep-Lluís; Céolin, René; Rietveld, Ivo B

2013-11-18

Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases. Copyright © 2013 Elsevier B.V. All rights reserved.

Feasibility and acceptability of a phase II randomized pharmacologic intervention for methamphetamine dependence in high-risk men who have sex with men

PubMed Central

Das, Moupali; Santos, Deirdre; Matheson, Tim; Santos, Glenn-Milo; Chu, Priscilla; Vittinghoff, Eric; Shoptaw, Steve; Colfax, Grant N.

2010-01-01

Objective To determine whether actively using, methamphetamine (meth)-dependent men who have sex with men (MSM) could be enrolled and retained in a pharmacologic intervention trial, and the degree to which participants would adhere to study procedures, including medication adherence. Study design Phase II randomized, double-blind trial of bupropion vs. placebo. Methods Thirty meth-dependent, sexually active MSM were randomized to receive daily bupropion XL 300 mg or placebo for 12 weeks. Participants received weekly substance use counseling, provided weekly urine specimens, and completed monthly audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps (the number of distinct MEMS cap openings divided by the number of expected doses) and self-report. Results Ninety percent completed the trial: 89% of monthly ACASIs were completed, 81% of study visits were attended, and 81% of urine samples were collected. Adherence by MEMS cap was 60% and by self-report was 81% and did not differ significantly by treatment assignment. The median number of positive urine samples was 5.5 out of a possible 11 (50%). Participants in both arms reported similar declines in the median number of sex partners (P = 0.52). No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment (P = 0.11). Conclusions It is feasible to enroll and retain actively using, meth-dependent MSM in a pharmacologic intervention. Bupropion was well tolerated. Study participation and retention rates were high, however, study drug medication adherence was only moderate. Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population. PMID:20397286

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.

PubMed

Andersen, Rikke; Donia, Marco; Ellebaek, Eva; Borch, Troels Holz; Kongsted, Per; Iversen, Trine Zeeberg; Hölmich, Lisbet Rosenkrantz; Hendel, Helle Westergren; Met, Özcan; Andersen, Mads Hald; Thor Straten, Per; Svane, Inge Marie

2016-08-01

Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR. ©2016 American Association for Cancer Research.

A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh

2009-07-15

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm{sup 2} postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) withmore » a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% {+-} 5% and 52% {+-} 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.« less

Safety and Efficacy of High-Dose Tamoxifen and Sulindac for Desmoid Tumor in Children: Results of a Children’s Oncology Group (COG) Phase II Study

PubMed Central

Skapek, Stephen X.; Anderson, James R.; Hill, D. Ashley; Henry, David; Spunt, Sheri L.; Meyer, William; Kao, Simon; Hoffer, Fredric A.; Grier, Holcombe E.; Hawkins, Douglas S.; Raney, R. Beverly

2015-01-01

Background Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children’s Oncology Group. Procedures Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Results Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10–18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23–0.48) and 96%, respectively. All three deaths were due to progressive DT. Conclusions Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. PMID:23281268

Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study.

PubMed

Skapek, Stephen X; Anderson, James R; Hill, D Ashley; Henry, David; Spunt, Sheri L; Meyer, William; Kao, Simon; Hoffer, Fredric A; Grier, Holcombe E; Hawkins, Douglas S; Raney, R Beverly

2013-07-01

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Copyright © 2012 Wiley Periodicals, Inc.

Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

PubMed

Yoshikawa, Takaki; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Kimura, Yutaka; Hirabayashi, Naoki; Mikata, Shoki; Iwahashi, Makoto; Fukushima, Ryoji; Takiguchi, Nobuhiro; Miyashiro, Isao; Morita, Satoshi; Miyashita, Yumi; Tsuburaya, Aakira; Sakamoto, Junichi

2014-01-01

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

PubMed

Kamiya, T; Uehara, K; Nakayama, G; Ishigure, K; Kobayashi, S; Hiramatsu, K; Nakayama, H; Yamashita, K; Sakamoto, E; Tojima, Y; Kawai, S; Kodera, Y; Nagino, M

2016-06-01

Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option. Copyright © 2016 Elsevier Ltd. All rights reserved.

ASR-9 processor augmentation card (9-PAC) phase II scan-scan correlator algorithms

DOT National Transportation Integrated Search

2001-04-26

The report documents the scan-scan correlator (tracker) algorithm developed for Phase II of the ASR-9 Processor Augmentation Card (9-PAC) project. The improved correlation and tracking algorithms in 9-PAC Phase II decrease the incidence of false-alar...

Cinacalcet: AMG 073, Calcimimetics--Amgen/NPS Pharmaceuticals, KRN 1493, NPS 1493.

PubMed

2003-01-01

Cinacalcet [AMG 073, KRN 1493, NPS 1493] is an orally active, second-generation calcimimetic compound licensed by NPS Pharmaceuticals to Amgen in the US for potential treatment of hyperparathyroidism (HPT). Cinacalcet modulates (increases the sensitivity of) calcium receptors on the surface of parathyroid cells thereby inhibiting the oversecretion of parathyroid hormone, which characterises HPT. It also represents a potentially significant advance for chronic kidney disease patients diagnosed with secondary HPT, a common yet serious metabolic disorder where parathyroid hormone levels are elevated. Patients with this disease can suffer from bone disease, bone pain and fractures, soft tissue calcification, vascular calcification and cardiovascular complications. Amgen has rights to develop and sell cinacalcet throughout the world except in Japan, Taiwan and China, where the compound was licensed to Kirin Brewery. Kirin is developing it as KRN 1493 in phase II clinical studies in Japan. In December 2001, commencement of a phase III clinical trial with cinacalcet for the treatment of secondary HPT, triggered a 3 million US dollars milestone payment to NPS Pharmaceuticals. In September 2003, submission of an NDA to the US FDA for cinacalcet for secondary HPT will be followed by a milestone payment of 6 million US dollars to NPS. NPS, Kirin and Amgen were also developing another compound, tecalcet, for HPT, but that project has been discontinued in favour of cinacalcet. In September 2003, Amgen submitted an NDA to the US FDA for secondary HPT in patients with chronic kidney disease. In April 2003, Amgen announced positive results from a phase III clinical trial with cinacalcet in patients with secondary HPT. In a clinical study in patients on dialysis suffering from the effects of chronically elevated levels parathyroid hormone, cinacalcet appeared to be safe and well tolerated and was significantly more effective than placebo. Two more additional efficacy studies with cinacalcet have also been completed. Phase II trials of cinacalcet in dialysis patients with secondary HPT and in patients with primary HPT were successfully completed.

"Barriers to Cognitive Behavioral Therapy Homework Completion Scale- Depression Version": Development and Psychometric Evaluation.

PubMed

Callan, Judith A; Dunbar-Jacob, Jacqueline; Sereika, Susan M; Stone, Clement; Fasiczka, Amy; Jarrett, Robin B; Thase, Michael E

2012-01-01

We conducted a two-phase study to develop and evaluate the psychometric properties of an instrument to identify barriers to Cognitive Behavioral Therapy (CBT) homework completion in a depressed sample. In Phase I, we developed an item pool by interviewing 20 depressed patients and 20 CBT therapists. In Phase II, we created and administered a draft instrument to 56 people with depression. Exploratory Factor Analysis revealed a 2-factor oblique solution of "Patient Factors" and "Therapy/Task Factors." Internal consistency coefficients ranged from .80 to .95. Temporal stability was demonstrated through Pearson correlations of .72 (for the therapist/task subscale) to .95 (for the patient subscale) over periods of time that ranged from 2 days to 3 weeks. The patient subscale was able to satisfactorily classify patients (75 to 79 %) with low and high adherence at both sessions. Specificity was .66 at both time points. Sensitivity was .80 at sessions B and .77 at session C. There were no consistent predictors of assignment compliance when measured by the Assignment Compliance Rating Scale (Primakoff, Epstein, & Covi, 1986). The Rating Scale and subscale scores did, however, correlate significantly with assignment non-compliance (.32 to .46).

“Barriers to Cognitive Behavioral Therapy Homework Completion Scale- Depression Version”: Development and Psychometric Evaluation

PubMed Central

Callan, Judith A.; Dunbar-Jacob, Jacqueline; Sereika, Susan M.; Stone, Clement; Fasiczka, Amy; Jarrett, Robin B.; Thase, Michael E.

2013-01-01

We conducted a two-phase study to develop and evaluate the psychometric properties of an instrument to identify barriers to Cognitive Behavioral Therapy (CBT) homework completion in a depressed sample. In Phase I, we developed an item pool by interviewing 20 depressed patients and 20 CBT therapists. In Phase II, we created and administered a draft instrument to 56 people with depression. Exploratory Factor Analysis revealed a 2-factor oblique solution of “Patient Factors” and “Therapy/Task Factors.” Internal consistency coefficients ranged from .80 to .95. Temporal stability was demonstrated through Pearson correlations of .72 (for the therapist/task subscale) to .95 (for the patient subscale) over periods of time that ranged from 2 days to 3 weeks. The patient subscale was able to satisfactorily classify patients (75 to 79 %) with low and high adherence at both sessions. Specificity was .66 at both time points. Sensitivity was .80 at sessions B and .77 at session C. There were no consistent predictors of assignment compliance when measured by the Assignment Compliance Rating Scale (Primakoff, Epstein, & Covi, 1986). The Rating Scale and subscale scores did, however, correlate significantly with assignment non-compliance (.32 to .46). PMID:24049556

UV light assisted decolorization of dark brown colored coffee effluent by photo-Fenton reaction.

PubMed

Tokumura, Masahiro; Ohta, Ayano; Znad, Hussein T; Kawase, Yoshinori

2006-12-01

The photochemical decolorization of coffee effluent has been examined by photo-Fenton (UV/Fe2+/H2O2) process. Effects of UV light intensity, initial coffee concentration, iron dose and H2O2 dose on the color removal of model coffee effluent have been investigated. The rate of decolorization increased with decreasing initial coffee effluent concentration. It was found that the Fe ion dose and UV light intensity enhanced the decolorization rate. The decolorization process of coffee effluent could be divided into three established phases. At the beginning of the photo-Fenton process, the instantaneous and significant increase in color of the solution was found (Phase-I). In the subsequent phase (Phase-II), the decolorization rate was initially fast and subsequently decreased. In Phase-III, the rate was accelerated and then the complete decolorization of model coffee effluent was achieved. In order to elucidate the mechanisms of coffee effluent color removal process, the concentration changes in Fe3+ and Fe2+ besides H2O2 were measured during the course of the photo-Fenton process. The rate-determining step in Phase-II was the photo-Fenton reaction or photoreduction of Fe3+. On the other hand, the decolorization process in Phase-III was highly affected by Fenton reaction or decomposition of H2O2 with Fe2+. About 93% mineralization of 250 mg L(-1) model coffee effluent was achieved after 250 min. A comparative study for TiO2, ZnO and photo-Fenton oxidation processes has been also carried out and the photo-Fenton process was found to be the most effective for color removal of coffee effluent.

Phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate in dogs with naturally occurring malignant tumors.

PubMed

Cai, Shuang; Zhang, Ti; Forrest, W C; Yang, Qiuhong; Groer, Chad; Mohr, Eva; Aires, Daniel J; Axiak-Bechtel, Sandra M; Flesner, Brian K; Henry, Carolyn J; Selting, Kimberly A; Tate, Deborah; Swarz, Jeffrey A; Bryan, Jeffrey N; Forrest, M Laird

2016-09-01

OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors. ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer. PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m(2), intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response. RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model. CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high. IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.

Phase II Study Evaluating the Addition of Cetuximab to the Concurrent Delivery of Weekly Carboplatin, Paclitaxel, and Daily Radiotherapy for Patients With Locally Advanced Squamous Cell Carcinomas of the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suntharalingam, Mohan, E-mail: msuntha@umm.edu; Kwok, Young; Goloubeva, Olga

Purpose: To report the mature data of a prospective Phase II trial designed to evaluate the efficacy of an epidermal growth factor receptor inhibitor cetuximab (CTX) added to the concurrent therapy of weekly paclitaxel/carboplatin (PC) and daily radiation therapy (RT). Methods and Materials: From 2005 to 2009, a total of 43 patients were enrolled in the study. The median follow-up was 31 months (range, 9-59 months). All patients had Stage III/IV disease at presentation, and 67% had oropharyngeal primaries. The weekly IV dose schedules were CTX 250 mg/m{sup 2} (400 mg/m{sup 2} IV loading dose 1 week before RT), paclitaxelmore » 40 mg/m{sup 2}, and carboplatin AUC 2. RT was given at 1.8 Gy per day to 70.2 Gy. Intensity-modulated RTwas used in 70% of cases. Results: All patients completed the planned RT dose, 74% without any treatment breaks. The planned CTX and PC cycles were completed in 70% (91% with at least seven of planned nine cycles) and 56% (93% with at least seven of planned eight cycles) of patients, respectively. Toxicity included Grade 3 mucositis (79%), rash (9%), leucopenia (19%), neutropenia (19%), and RT dermatitis (16%). The complete response (CR) rate at the completion of therapy was 84%. The estimated 3-year local regional control rate was 72%. Six patients with an initial CR subsequently experienced a local recurrence, 10 patients experienced distant progression. The median overall survival and disease-free survivals have not been reached. The 3-year actuarial overall survival and disease-free survival were 59% and 58%, respectively. Conclusions: The addition of CTX to weekly PC and daily RT was well tolerated and resulted in encouraging local control and survival rates.« less

Supplement Analysis for the Watershed Management Program Final EIS (DOE EIS /SA-156) - Upper Salmon River Anadromous Fish Passage Improvement Projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, Carl J.

2004-07-13

BPA proposes to fund IDFG to plan and complete construction of fish passage improvements and water conservation activities that are contained within IDFG’s Statement of Work (SOW) for the period 7/1/04 to 6/30/05. The funding request contained in their SOW is part of an ongoing IDFG effort to fund anadromous fish passage projects that fall outside the scope of the Mitchell Act. The proposed SOW activities fall within the following four categories: Phase I-Planning and Design (gather data, perform investigations, and exchange information; perform surveys and assessments to be compliant; survey project sites and perform engineering designs; perform contract andmore » project management); Phase II-Construction and Implementation (procure materials and supplies, prepare contracts and solicit bids, plant native seedlings, complete capital improvements); Phase III-Operation and Maintenance (maintain office operations); and Phase IV- Monitoring and Evaluation (monitor and evaluate post-project effects, reporting). The SOW culminates with proposed construction of 18 capital improvement projects (Table 1 attached). The types of capital improvements include: screening gravity water diversions; consolidating and/or eliminating ditches; evaluating and screening pump diversions; evaluating and implementing water conservation activities; constructing screens along migration routes and rearing areas for hatchery and wild salmon; improving upstream and downstream passage for anadromous fish; and maximize benefits to aquatic habitat. Because each of the proposed projects in the SOW is still in the planning stages, the specifics of each still need to be completed.« less

Mechanisms of blood pressure alterations in response to the Valsalva maneuver in postural tachycardia syndrome

NASA Technical Reports Server (NTRS)

Sandroni, P.; Novak, V.; Opfer-Gehrking, T. L.; Huck, C. A.; Low, P. A.

2000-01-01

The postural tachycardia syndrome (POTS) is characterized clinically by orthostatic lightheadedness and tachycardia. When these patients perform a Valsalva maneuver, there is an excessive blood pressure increment after cessation of the maneuver (phase IV) that is sometimes associated with headaches. It is not known whether excessive phase IV is due to excessive peripheral vascular tone (an alpha-adrenergic mechanism) or is a manifestation of increased beta-adrenergic tone (hyperadrenergic state). The authors undertook a pharmacologic study evaluating the effect of intravenous phentolamine (alpha-adrenergic antagonist) and propranolol (beta-adrenergic antagonist) on the different phases of the Valsalva maneuver in a group of patients with POTS and age-matched normal control subjects. Patients with POTS had mean phases, when compared with controls, that were characterized by more negative II_E (p = 0.07), smaller II_L (p = 0.04), and significantly larger phase IV (p = 0.001). The effect of phentolamine was qualitatively and quantitatively different in POTS when compared with controls. Ten mg phentolamine in controls resulted in a significant accentuation of phase II_E (p = 0.001), attenuation of phase II_L (p = 0.002), and increase of phase IV (57.6 vs 30.7 mm Hg; p = 0.025). These changes resembled those of patients with POTS at baseline. In patients with POTS, the phase II abnormalities, already present, were further accentuated (p <0.001), and phase IV became smaller (50.6 vs 73.8 mm Hg; p = 0.09). Propranolol had no significant effect on phases II_E and II_L, but significantly reduced phase IV in both controls (p <0.05) and in patients with POTS (p <0.001) and improved the headache symptoms, when present, during and after phase IV. The authors conclude that phase IV is mainly under beta-adrenergic regulation and that the exaggerated phase IV in POTS is a result of a hyperadrenergic state.

TNX GeoSiphon Cell (TGSC-1) Phase II Single Cell Deployment/Demonstration Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phifer, M.A.

1999-04-15

This Phase II final report documents the Phase II testing conducted from June 18, 1998 through November 13, 1998, and it focuses on the application of the siphon technology as a sub-component of the overall GeoSiphon Cell technology. [Q-TPL-T-00004

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

First results of GERDA Phase II and consistency with background models

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode1, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-01-01

The GERDA (GERmanium Detector Array) is an experiment for the search of neutrinoless double beta decay (0νββ) in 76Ge, located at Laboratori Nazionali del Gran Sasso of INFN (Italy). GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase II of data-taking started in Dec 2015 and is currently ongoing. In Phase II 35 kg of germanium detectors enriched in 76Ge including thirty newly produced Broad Energy Germanium (BEGe) detectors is operating to reach an exposure of 100 kg·yr within about 3 years data taking. The design goal of Phase II is to reduce the background by one order of magnitude to get the sensitivity for T1/20ν = O≤ft( {{{10}26}} \\right){{ yr}}. To achieve the necessary background reduction, the setup was complemented with LAr veto. Analysis of the background spectrum of Phase II demonstrates consistency with the background models. Furthermore 226Ra and 232Th contamination levels consistent with screening results. In the first Phase II data release we found no hint for a 0νββ decay signal and place a limit of this process T1/20ν > 5.3 \\cdot {1025} yr (90% C.L., sensitivity 4.0·1025 yr). First results of GERDA Phase II will be presented.

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

PubMed

Dutton, P; Love, S B; Billingham, L; Hassan, A B

2018-05-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

Methyl chloride via oxyhydrochlorination of methane: A building block for chemicals and fuels from natural gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, R.L.; Brown, S.S.D.; Ferguson, S.P.

1995-12-31

The objectives of this program are to (a) develop a process for converting natural gas to methyl chloride via an oxyhydrochlorination route using highly selective, stable catalysts in a fixed-bed, (b) design a reactor capable of removing the large amount of heat generated in the process so as to control the reaction, (c) develop a recovery system capable of removing the methyl chloride from the product stream and (d) determine the economics and commercial viability of the process. The general approach has been as follows: (a) design and build a laboratory scale reactor, (b) define and synthesize suitable OHC catalystsmore » for evaluation, (c) select first generation OHC catalyst for Process Development Unit (PDU) trials, (d) design, construct and startup PDU, (e) evaluate packed bed reactor design, (f) optimize process, in particular, product recovery operations, (g) determine economics of process, (h) complete preliminary engineering design for Phase II and (i) make scale-up decision and formulate business plan for Phase II. Conclusions regarding process development and catalyst development are presented.« less

Phase II trial of CH5424802 (alectinib hydrochloride) for recurrent or refractory ALK-positive anaplastic large cell lymphoma: study protocol for a non-randomized non-controlled trial.

PubMed

Nagai, Hirokazu; Fukano, Reiji; Sekimizu, Masahiro; Kada, Akiko; M Saito, Akiko; Asada, Ryuta; Mori, Tetsuya

2017-08-01

Currently, a standard therapy has not been established for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. While there are many treatment options, such as hematopoietic stem cell transplantation, patients with resistant disease to conventional chemotherapies have particularly poor prognosis. There is urgent need to develop new drugs because of the lack of a standard therapy and poor prognoses. This phase II trial is designed for evaluating the efficacy and safety of alectinib hydrochloride for patients with recurrent or refractory anaplastic lymphoma kinase -positive anaplastic large cell lymphoma. The primary endpoint is the response rate according to the Revised Response Criteria for Malignant Lymphoma. The secondary endpoints are pharmacokinetics, safety in children, complete response rate, response duration, progression-free survival, event-free survival, overall survival, and adverse events. The results of this trial will be the pivotal data for the drug approval of alectinib hydrochloride for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study.

PubMed

Brandes, Alba A; Ermani, Mario; Basso, Umberto; Paris, Myriam K; Lumachi, Franco; Berti, Franco; Amistà, Pietro; Gardiman, Marina; Iuzzolino, Paolo; Turazzi, Sergio; Monfardini, Silvio

2002-01-01

To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m(2)/daily for 5 days every 4 weeks. The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%), respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7-31%). TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM. Copyright 2002 S. Karger AG, Basel

Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center

PubMed Central

Gibb, Adam; Jones, Craig; Bloor, Adrian; Kulkarni, Samar; Illidge, Tim; Linton, Kim; Radford, John

2013-01-01

The CD30-targeted agent brentuximab vedotin has shown impressive activity in relapsed/refractory Hodgkin lymphoma and anaplastic large cell lymphoma in phase II studies. We have treated 24 patients with relapsed/refratory disease enrolled onto a Named Patient Programme during 2010-11 at a single UK center. Overall response rate across all histologies was 67% (Hodgkin 72%; anaplastic large cell 60%), complete response rate 25% (Hodgkin 17%; anaplastic large cell 60%), median progression-free survival 5.1 months, and toxicity mild to moderate in the majority of cases. Six patients proceeded to allogeneic transplantation and one patient awaits this procedure. These results are similar to phase II data and show that brentuximab vedotin provides a bridge to allogeneic transplantation in approximately one quarter of patients refractory to conventional salvage therapies. Best response was seen after four doses, so consideration of allogeneic transplantation should be made early and scheduled following the first assessment indicating response. PMID:23065511

Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain: A Phase II Randomized, Double-Blind, Placebo-Controlled Extension Study.

PubMed

Sanga, Panna; Katz, Nathaniel; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Haeussler, Juergen; Thipphawong, John

2017-04-01

To evaluate the long-term safety and efficacy of fulranumab in patients with knee or hip pain caused by moderate-to-severe chronic osteoarthritis (OA). In this phase II double-blind, placebo-controlled extension study, patients who were randomized in equal proportions to receive subcutaneous doses of either placebo or fulranumab (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, or 10 mg every 8 weeks) in the 12-week double-blind efficacy phase and who completed this double-blind efficacy phase were eligible to continue the dosage throughout a 92-week double-blind extension phase, followed by a 24-week posttreatment follow-up period. Safety assessments included evaluation of treatment-emergent adverse events (TEAEs), pre-identified AEs of interest, and joint replacements. Efficacy assessments included changes from baseline to the end of the double-blind extension phase in scores on the patient's global assessment and the pain and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index. Overall, 401 of the 423 patients who completed the 12-week double-blind efficacy phase entered the extension study. Long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment (1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks) as compared with placebo. Similar percentages of patients in both groups experienced TEAEs (88% taking placebo and 91% taking fulranumab; all phases). Across all fulranumab groups, arthralgia (21%) and OA (18%) (e.g., exacerbation of OA pain) were the most common TEAEs. The most common serious TEAEs were the requirement for knee (10%) and hip (7%) arthroplasty, with 80% occurring during the posttreatment follow-up period. Neurologic-related TEAEs (28%; all phases) were generally mild-to-moderate. Overall, 81 joint replacements were performed in 71 patients (8 [11%] receiving placebo and 63 [89%] receiving fulranumab); 15 patients (21%) had rapid progression of OA (RPOA). All cases of RPOA occurred in fulranumab-treated patients who were concurrently receiving nonsteroidal antiinflammatory drugs and occurred in joints with preexisting OA. Long-term treatment with fulranumab was generally well-tolerated and efficacious. RPOA was observed as a safety signal. Future studies are warranted to demonstrate whether the risk of RPOA can be reduced in patients taking fulranumab. © 2016, American College of Rheumatology.

A model of irreversible jam formation in dense traffic

NASA Astrophysics Data System (ADS)

Brankov, J. G.; Bunzarova, N. Zh.; Pesheva, N. C.; Priezzhev, V. B.

2018-03-01

We study an one-dimensional stochastic model of vehicular traffic on open segments of a single-lane road of finite size L. The vehicles obey a stochastic discrete-time dynamics which is a limiting case of the generalized Totally Asymmetric Simple Exclusion Process. This dynamics has been previously used by Bunzarova and Pesheva (2017) for an one-dimensional model of irreversible aggregation. The model was shown to have three stationary phases: a many-particle one, MP, a phase with completely filled configuration, CF, and a boundary perturbed MP+CF phase, depending on the values of the particle injection (α), ejection (β) and hopping (p) probabilities. Here we extend the results for the stationary properties of the MP+CF phase, by deriving exact expressions for the local density at the first site of the chain and the probability P(1) of a completely jammed configuration. The unusual phase transition, characterized by jumps in both the bulk density and the current (in the thermodynamic limit), as α crosses the boundary α = p from the MP to the CF phase, is explained by the finite-size behavior of P(1). By using a random walk theory, we find that, when α approaches from below the boundary α = p, three different regimes appear, as the size L → ∞: (i) the lifetime of the gap between the rightmost clusters is of the order O(L) in the MP phase; (ii) small jams, separated by gaps with lifetime O(1) , exist in the MP+CF phase close to the left chain boundary; and (iii) when β = p, the jams are divided by gaps with lifetime of the order O(L 1 / 2) . These results are supported by extensive Monte Carlo calculations.

[Long-term physical activity after a myocardial infarction : a permanent challenge].

PubMed

Tessitore, Elena; Sigaud, Philippe; Meyer, Philippe; Mach, François

2017-05-24

Cardiac rehabilitation is a well-defined multidisciplinary program with the objective to reduce mortality and morbidity, while also improving the exercise capacity and quality of life of the patient following a myocardial infarction. Despite the fact that a cardiovascular rehabilitation program is now recommended by international guidelines for all patients who have suffered from an acute coronary syndrome, only half of all patients actually participate to such a program in Switzerland. Even worse, especially when taking into consideration the population in Geneva, less than 5 % of patients follow a long-term cardiac maintenance program (phase III). Since 2015, our project has been to encourage patients who have completed a phase II cardiac rehabilitation program, to resume regular physical activity in the long term.

Addressing the immunopathogenesis of atopic dermatitis: advances in topical and systemic treatment.

PubMed

Eichenfield, Lawrence F; Stein Gold, Linda F

2017-03-01

Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406. The phase III clinical trial results of the systemic medication dupilumab, an inhibitor of the IL-4 receptor α subunit (which inhibits both IL-4 and IL-13 signaling), are currently being reviewed by the FDA. ©2017 Frontline Medical Communications.

Phenomenology of Polymorphism, III: p, TDiagram and Stability of Piracetam Polymorphs

NASA Astrophysics Data System (ADS)

Céolin, R.; Agafonov, V.; Louër, D.; Dzyabchenko, V. A.; Toscani, S.; Cense, J. M.

1996-02-01

The nootropic drug Piracetam is known to crystallize in three phases. In order to obtain their stability hierarchy from sublimation pressure inequalities, the drawing of a topologicalp,Tdiagram was attempted. For such a purpose and also for quality control, crystallographic and thermodynamic data were required. Powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC) were used. Molecular energy calculations were performed. Phase I melts at 426 K (ΔfusH(I) = +180 J·g-1). Phase II transforms into Phase I at 399 K (Δ(II→I)H= +24 J·g-1). Phase III transforms into phase I at 392 K (Δ(III→I)H= +28 J·g-1) or melts at 412 K (ΔfusH(III) = +210 J·g-1). Thep,Tdiagram shows that phase I is stable at higher temperature and phase II at lower temperature, like phase III, which is stable under high pressure. At room temperature, phase II is the more stable form, and phase I the less stable one. This agrees with the spontaneous I → II transformation observed at 298 K within a few hours, and with lattice energies, calculated previously. Molecular energy calculations and crystal structure comparison show how intermolecular hydrogen bonds and H-bonded dimers, in phases II and III, may stabilize conformations higher in energy than those of the isolated molecule and of phase I.

New developments in instrumentation at the W. M. Keck Observatory

NASA Astrophysics Data System (ADS)

Adkins, Sean M.; Armandroff, Taft E.; Fitzgerald, Michael P.; Johnson, James; Larkin, James E.; Lewis, Hilton A.; Martin, Christopher; Matthews, Keith Y.; Prochaska, J. X.; Wizinowich, Peter

2014-07-01

The W. M. Keck Observatory continues to develop new capabilities in support of our science driven strategic plan which emphasizes leadership in key areas of observational astronomy. This leadership is a key component of the scientific productivity of our observing community and depends on our ability to develop new instrumentation, upgrades to existing instrumentation, and upgrades to supporting infrastructure at the observatory. In this paper we describe the as measured performance of projects completed in 2014 and the expected performance of projects currently in the development or construction phases. Projects reaching completion in 2014 include a near-IR tip/tilt sensor for the Keck I adaptive optics system, a new center launch system for the Keck II laser guide star facility, and NIRES, a near-IR Echelle spectrograph for the Keck II telescope. Projects in development include a new seeing limited integral field spectrograph for the visible wavelength range called the Keck Cosmic Web Imager, a deployable tertiary mirror for the Keck I telescope, upgrades to the spectrograph detector and the imager of the OSIRIS instrument, and an upgrade to the telescope control systems on both Keck telescopes.

A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isobe, Koichi; Kagami, Yoshikazu; Higuchi, Keiko

2007-11-15

Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. Themore » median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.« less

Benefits and Sustainability of a Learning Collaborative for Implementation of Treat to Target in Rheumatoid Arthritis: Results of the TRACTION Trial Phase II.

PubMed

Solomon, Daniel H; Lu, Bing; Yu, Zhi; Corrigan, Cassandra; Harrold, Leslie R; Smolen, Josef S; Fraenkel, Liana; Katz, Jeffrey N; Losina, Elena

2018-01-05

We conducted a two-phase randomized controlled trial of a Learning Collaborative (LC) to facilitate implementation of treat to target (TTT) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of TTT in Phase I. Herein, we report on a second 9 months (Phase II) where we examined maintenance of response in Phase I and predictors of greater improvement in TTT adherence. We recruited 11 rheumatology sites and randomized them to either receive the LC during Phase I or to a wait-list control group that received the LC intervention during Phase II. The outcome was change in TTT implementation score (0 to 100, 100 is best) from pre- to post-intervention. TTT implementation score is defined as a percent of components documented in visit notes. Analyses examined: 1) the extent that the Phase I intervention teams sustained improvement in TTT; and, 2) predictors of TTT improvement. The analysis included 636 RA patients. At baseline, mean TTT implementation score was 11% in Phase I intervention sites and 13% in Phase II sites. After the intervention, TTT implementation score improved to 57% in the Phase I intervention sites and to 58% in the Phase II sites. Intervention sites from Phase I sustained the improvement during the Phase II (52%). Predictors of greater TTT improvement included only having rheumatologist providers at the site, academic affiliation of the site, fewer providers per site, and the rheumatologist provider being a trainee. Improvement in TTT remained relatively stable over a post-intervention period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

More Constraints on the Physical Conditions of the Kinematically Complex, Multiphase Absorption Line System at z=0.93 toward PG1206+459

NASA Astrophysics Data System (ADS)

Rosenwasser, Ben; Muzahid, Sowgat; Norris, Jackson; Charlton, Jane C.

2015-01-01

We present the results of photo- and collisional ionization modeling of the strong MgII absorption system at redshift z~0.93 towards the quasar PG1206+459. This system has been extensively studied over the last two decades (Churchill & Charlton 1999; Ding et al. 2003; Tripp et al. 2011) using a combination of spectra from Keck/HIRES, HST/FOS, HST/STIS, and HST/COS. Here we present newconstraints using the most complete spectral coverage including more recent observations of OVI and the Lyman series from HST/COS. Numerous absorption components are seen over a large velocity spread (~1500km/s), and multiple ionization phases are required to account for the detected transitions, which include MgI, MgII, FeII, SiII, SiIII, SiIV, CII, CIII, CIV, SIII, SIV, SV, SVI, NIII, NIV, NV, OIII, OIV, OV, OVI, and NeVIII. Considering the new constraints, we revisit the question of the physical nature of the structures that produce this absorber.

Cellulose-lanthanum hydroxide nanocomposite as a selective marker for detection of toxic copper

PubMed Central

2014-01-01

In this current report, a simple, reliable, and rapid method based on modifying the cellulose surface by doping it with different percentages of lanthanum hydroxide (i.e., 1% La(OH)3-cellulose (LC), 5% La(OH)3-cellulose (LC2), and 10% La(OH)3-cellulose (LC3)) was proposed as a selective marker for detection of copper (Cu(II)) in aqueous medium. Surface properties of the newly modified cellulose phases were confirmed by Fourier transform infrared spectroscopy, field emission scanning electron microscope, energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopic analysis. The effect of pH on the adsorption of modified cellulose phases for Cu(II) was evaluated, and LC3 was found to be the most selective for Cu(II) at pH 6.0. Other parameters, influencing the maximum uptake of Cu(II) on LC3, were also investigated for a deeper mechanistic understanding of the adsorption phenomena. Results showed that the adsorption capacity for Cu(II) was improved by 211% on the LC3 phase as compared to diethylaminoethyl cellulose phase after only 2 h contact time. Adsorption isotherm data established that the adsorption process nature was monolayer with a homogeneous adsorbent surface. Results displayed that the adsorption of Cu(II) onto the LC3 phase obeyed a pseudo-second-order kinetic model. Selectivity studies toward eight metal ions, i.e., Cd(II), Co(II), Cr(III), Cr(VI), Cu(II), Fe(III), Ni(II), and Zn(II), were further performed at the optimized pH value. Based on the selectivity study, it was found that Cu(II) is highly selective toward the LC3 phase. Moreover, the efficiency of the proposed method was supported by implementing it to real environmental water samples with adequate results. PMID:25258599

MECHANISM AND KINETICS OF THE FORMATION OF NOX AND OTHER COMBUSTION POLLUTANTS. PHASE II. MODIFIED COMBUSTION

EPA Science Inventory

The report gives Phase II results of a combined experimental/theoretical study to define the mechanisms and kinetics of the formation of NOx and other combustion pollutants. Two experimental devices were used in Phase II. A special flat-flame burner with a controlled-temperature ...

76 FR 3624 - Milford Wind Corridor Phase II, LLC; Supplemental Notice That Initial Market-Based Rate Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER11-2657-000] Milford Wind Corridor Phase II, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for... proceeding Milford Wind Corridor Phase II, LLC's application for market-based rate authority, with an...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

Doping-induced disappearance of ice II from water's phase diagram

NASA Astrophysics Data System (ADS)

Shephard, Jacob J.; Slater, Ben; Harvey, Peter; Hart, Martin; Bull, Craig L.; Bramwell, Steven T.; Salzmann, Christoph G.

2018-06-01

Water and the many phases of ice display a plethora of complex physical properties and phase relationships1-4 that are of paramount importance in a range of settings including processes in Earth's hydrosphere, the geology of icy moons, industry and even the evolution of life. Well-known examples include the unusual behaviour of supercooled water2, the emergent ferroelectric ordering in ice films4 and the fact that the `ordinary' ice Ih floats on water. We report the intriguing observation that ice II, one of the high-pressure phases of ice, disappears in a selective fashion from water's phase diagram following the addition of small amounts of ammonium fluoride. This finding exposes the strict topologically constrained nature of the ice II hydrogen-bond network, which is not found for the competing phases. In analogy to the behaviour of frustrated magnets5, the presence of the exceptional ice II is argued to have a wider impact on water's phase diagram, potentially explaining its general tendency to display anomalous behaviour. Furthermore, the impurity-induced disappearance of ice II raises the prospect that specific dopants may not only be able to suppress certain phases but also induce the formation of new phases of ice in future studies.

Complete Hamiltonian analysis of cosmological perturbations at all orders II: non-canonical scalar field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nandi, Debottam; Shankaranarayanan, S., E-mail: debottam@iisertvm.ac.in, E-mail: shanki@iisertvm.ac.in

2016-10-01

In this work, we present a consistent Hamiltonian analysis of cosmological perturbations for generalized non-canonical scalar fields. In order to do so, we introduce a new phase-space variable that is uniquely defined for different non-canonical scalar fields. We also show that this is the simplest and efficient way of expressing the Hamiltonian. We extend the Hamiltonian approach of [1] to non-canonical scalar field and obtain an unique expression of speed of sound in terms of phase-space variable. In order to invert generalized phase-space Hamilton's equations to Euler-Lagrange equations of motion, we prescribe a general inversion formulae and show that ourmore » approach for non-canonical scalar field is consistent. We also obtain the third and fourth order interaction Hamiltonian for generalized non-canonical scalar fields and briefly discuss the extension of our method to generalized Galilean scalar fields.« less

Improved electroacoustic dewatering (EAD) belt press for food products. Phase 3, Technical progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-02-01

Battelle`s electroacoustic dewatering (EAD) process improves the performance of mechanical dewatering processes for several food products (such as corn fiber) by superimposing electric and ultrasonic fields. EAD has the potential to save 0.027 to 0.035 quad/yr energy by 1995 in the food processing industry, which consumed 0.15 to 0.18 quad in 1986. This report covers Phase III for demonstrating the EAD prototype on corn wet milling products (corn fiber and gluten); only Task 1 (prototype preparation and planning) was completed. EAD performance was examined in the laboratory; availability of a test site was examined. The single-roll, postdewatering EAD belt pressmore » prototype can accept material predewatered by a screw press, centrifuge, or any other mechanical dewatering device. The two-belt system, utilizing a copper-polymer cathode belt, performed as well as the three-belt system used in Phase II.« less

Thrombopoietic agents.

PubMed

Stasi, Roberto; Bosworth, Jenny; Rhodes, Elizabeth; Shannon, Muriel S; Willis, Fenella; Gordon-Smith, Edward C

2010-01-01

Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development. Copyright 2010 Elsevier Ltd. All rights reserved.

The Dengue Vaccine Pipeline: Implications for the Future of Dengue Control

PubMed Central

Schwartz, Lauren M.; Halloran, M. Elizabeth; Durbin, Anna P.; Longini, Ira M.

2015-01-01

Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective tetravalent dengue vaccines is an attractive addition to prevent disease or minimize the possibility of epidemics. There are currently no licensed dengue vaccines. This review summarizes the current status of all dengue vaccine candidates in clinical evaluation. Currently five candidate vaccines are in human clinical trials. One has completed two Phase III trials, two are in Phase II trials, and three are in Phase I testing. PMID:25989449

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL).

PubMed

Di Renzo, Nicola; Montanini, Antonella; Mannina, Donato; Dondi, Alessandra; Muci, Stefania; Mancuso, Salvatrice; De Paolis, M Rosaria; Plati, Caterina; Stelitano, Caterina; Patti, Catia; Olivieri, Attilio; Liardo, Eliana; Buda, Gabriele; Cantaffa, Renato; Federico, Massimo

2011-10-01

The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects present for a specific study phase may have been masked by combining protocols into phase groupings. Presence of informative censoring, such as withdrawal of some protocols from development if they began showing signs of lost interest among investigators, complicates interpretation of Kaplan-Meier estimates. Because this study constitutes a retrospective examination over an extended period of time, it does not allow for the precise identification of relative factors impacting timing. Conclusions Delays not only increase the time and cost to complete clinical trials, but they also diminish their usefulness by failing to answer research questions in time. We believe that research analyzing the time spent traversing defined intervals across the clinical trial protocol development and implementation continuum can stimulate business process analyses and reengineering efforts that could lead to reductions in the time from clinical trial concept to results, thereby accelerating progress in clinical research. PMID:24980279

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period.

PubMed

Masic, U; Harrold, J A; Christiansen, P; Cuthbertson, D J; Hardman, C A; Robinson, E; Halford, J C G

2017-02-01

Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n=116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n=50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Clinical Trials: NCT02591134; registered: 23.10.2015. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

PubMed

McDonald, S A; Hutchinson, S J; Innes, H A; Allen, S; Bramley, P; Bhattacharyya, D; Carman, W; Dillon, J F; Fox, R; Fraser, A; Goldberg, D J; Kennedy, N; Mills, P R; Morris, J; Stanley, A J; Wilks, D; Hayes, P C

2014-05-01

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect. © 2013 John Wiley & Sons Ltd.

Treatment of irradiated graphite from French Bugey reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Howard; Laurent, Gerard

In 2008, following the general French plan for nuclear waste management, Electricite de France attempted to find for irradiated graphite an alternative solution to direct storage at the low-activity long-life storage center in France managed by the national agency for wastes (ANDRA). EDF management requested that its engineering arm, EDF CIDEN, study the graphite treatment alternatives to direct storage. In mid-2008, this study revealed the potential advantage for EDF to use a steam reforming process known as Thermal Organic Reduction, 'THOR' (owned by Studsvik, Inc., USA), to treat or destroy the graphite matrix and limit the quantity of secondary wastemore » to be stored. In late 2009, EDF began a test program with Studsvik to determine if the THOR steam reforming process could be used to destroy the graphite. The program also sought to determine if the graphite could be treated to release the bulk of activity while minimizing the gasification of the bulk mass of the graphite. In October 2009, tests with non-irradiated graphite were completed and demonstrated destruction of a graphite matrix by the THOR process at satisfactory rates. After gasifying the graphite, focus shifted to the effect of roasting graphite at high temperatures in inert gases with low concentrations of oxidizing gases to preferentially remove volatile radionuclides while minimizing the graphite mass loss to 5%. A radioactive graphite sleeve was imported from France to the US for these tests. Completed in April 2010, 'Phase I' of testing showed that the process removed >99% of H-3 and 46% of C-14 with <6% mass loss. Completed in September 2011, 'Phase II' testing achieved increased removals as high as 80% C-14. During Phase II, it was also discovered that roasting in a reducing atmosphere helped to limit the oxidation of the graphite. Future work seeks to explore the effects of reducing gases to limit the bulk oxidation of graphite. If the graphite could be decontaminated of long-lived radionuclides up to 95% for C-14 while minimizing mass loss to <5%, this would minimize the volume of any secondary waste streams and potentially lower the waste class of the larger bulk of graphite. Alternatively, if up to 95% decontamination of C-14 is achieved, the graphite may be completely gasified which could result in lower disposal. (authors)« less

Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukeaemia (OPAL): a randomized open-label phase 2 study

PubMed Central

Cortes, Jorge; Feldman, Eric; Yee, Karen; Rizzieri, David; Advani, Anjali S.; Charman, Anthony; Spruyt, Richard; Toal, Martin; Kantarjian, Hagop

2017-01-01

Background Tosedostat is a novel oral aminopeptidase inhibitor with clinical activity in a previous phase I/II study in elderly patients with relapsed/refractory acute myeloid leukaemia (RR AML). We present the results of a randomised phase II study comparing two dosing regimes of tosedostat. Methods Patients aged ≥60 years with AML with relapse after a first complete remission (CR) lasting up to 12 months, or no prior CR, were randomised to receive as first salvage tosedostat 120 mg once daily for 6 months or 240 mg once daily for 2 months followed by 120 mg for 4 months. The primary endpoint was the proportion of patients who obtained a Complete Remission or Complete Remission with incomplete Platelet Recovery. The study was analysed on an intention to treat basis. The study was registered on clintrials.gov (NCT00780598) and the final study visit occurred in March 2011. Findings Seventy-three patients were treated with tosedostat. Seven patients (10%) achieved CR or a complete remission with incomplete platelet recovery (CRp): 2 of 38 (5%) in the 120 mg group and 5 of 35 (14%) in the 240 mg→120 mg group. The most common adverse events at grade 3 or worse were febrile neutropenia which occurred in 21/73 (29%) patients overall, 11/38 (29%) in the 120 mg group and 10/35 (29%) of the 240 mg→120 mg group, thrombocytopenia (16, 22%; 8, 21% and 8, 23%), fatigue (15, 21%; 7, 18% and 8, 23%), dyspnoea (12, 16%; 5, 13% and 7, 20%), pneumonia (10, 14%; 4, 11% and 6, 17%). There were 5 adverse events with an outcome of death, 3 in the 120 mg group and 2 in the 240 mg→120 mg group. The events were acute hepatitis, respiratory failure, pneumonia, atrial fibrillation and left ventricular dysfunction. Interpretation Tosedostat, at either dose schedule, has efficacy in older patients with relapsed or refractory AML, particularly those with prior myelodysplastic syndromes (MDS) or prior hypomethylating agent therapy. Additional studies of tosedostat including combination with hypomethylating agents and low dose cytarabine in patients with high risk MDS and AML are ongoing and/or planned. Funding The OPAL study was funded by Chroma Therapeutics Ltd, Abingdon, UK. PMID:23453583

Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial.

PubMed

Ren, Xiao-Cang; Wang, Quan-Yu; Zhang, Rui; Chen, Xue-Ji; Wang, Na; Liu, Yue-E; Zong, Jie; Guo, Zhi-Jun; Wang, Dong-Ying; Lin, Qiang

2016-04-23

Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols. NCT02720614, the date of registration: March 23, 2016.

Impact of sleep, screen time, depression and stress on weight change in the intensive weight loss phase of the LIFE study.

PubMed

Elder, C R; Gullion, C M; Funk, K L; Debar, L L; Lindberg, N M; Stevens, V J

2012-01-01

The LIFE study is a two-phase randomized clinical trial comparing two approaches to maintaining weight loss following guided weight loss. Phase I provided a nonrandomized intensive 6-month behavioral weight loss intervention to 472 obese (body mass index 30-50) adult participants. Phase II is the randomized weight loss maintenance portion of the study. This paper focuses on Phase I measures of sleep, screen time, depression and stress. The Phase I intervention consisted of 22 group sessions led over 26 weeks by behavioral counselors. Recommendations included reducing dietary intake by 500 calories per day, adopting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and increasing physical exercise to at least 180 min per week. Measures reported here are sleep time, insomnia, screen time, depression and stress at entry and post-weight loss intervention follow-up. The mean weight loss for all participants over the intensive Phase I weight loss intervention was 6.3 kg (s.d. 7.1). Sixty percent (N=285) of participants lost at least 4.5 kg (10 lbs) and were randomized into Phase II. Participants (N=472) attended a mean of 73.1% (s.d. 26.7) of sessions, completed 5.1 (s.d. 1.9) daily food records/week, and reported 195.1 min (s.d. 123.1) of exercise per week. Using logistic regression, sleep time (quadratic trend, P=0.030) and lower stress (P=0.024) at entry predicted success in the weight loss program, and lower stress predicted greater weight loss during Phase I (P=0.021). In addition, weight loss was significantly correlated with declines in stress (P=0.048) and depression (P=0.035). Results suggest that clinicians and investigators might consider targeting sleep, depression and stress as part of a behavioral weight loss intervention.

Maximizing return on socioeconomic investment in phase II proof-of-concept trials.

PubMed

Chen, Cong; Beckman, Robert A

2014-04-01

Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials. ©2014 AACR.

Development of advanced blanket performance under irradiation and system integration through JUPITER-II project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, Katsunori; Kohyama, Akira; Tanaka, Satoru

This report describes an outline of the activities of the JUPITER-II collaboration (japan-USA program of Irradiation/Integration test for Fusion Research-II), Which has bee carried out through six years (2001-2006) under Phase 4 of the collabroation implemented by Amendment 4 of Annex 1 to the DOE (United States Department of Energy)-MEXT (Ministry of Education ,Culture,Sports,Science and Technology) Cooperation. This program followed the RTNS-II Program (Phase1:1982-4986), the FFTF/MOTA Program (Phase2:1987-1994) and the JUPITER Program (Phase 3: 1995-2000) [1].

Upgrade for Phase II of the Gerda experiment

NASA Astrophysics Data System (ADS)

Agostini, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hiller, R.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Ioannucci, L.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kermaïdic, Y.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Nisi, S.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Ransom, C.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schütz, A.-K.; Schulz, O.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zsigmond, A. J.; Zuber, K.; Zuzel, G.

2018-05-01

The Gerda collaboration is performing a sensitive search for neutrinoless double beta decay of ^{76}Ge at the INFN Laboratori Nazionali del Gran Sasso, Italy. The upgrade of the Gerda experiment from Phase I to Phase II has been concluded in December 2015. The first Phase II data release shows that the goal to suppress the background by one order of magnitude compared to Phase I has been achieved. Gerda is thus the first experiment that will remain "background-free" up to its design exposure (100 kg year). It will reach thereby a half-life sensitivity of more than 10^{26} year within 3 years of data collection. This paper describes in detail the modifications and improvements of the experimental setup for Phase II and discusses the performance of individual detector components.

40 CFR 80.45 - Complex emissions model.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCW% = Percentage change in winter VOC emissions from baseline levels (8) Phase II total VOC emissions... its domain Phase I = The years 1995-1999 Phase II = Year 2000 and beyond (b) Weightings and baselines... appropriate pollutant and Phase: Table 1—Normal and Higher Emitter Weightings for Exhaust Emissions Phase I...

The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.

PubMed

Nieuwenhuizen, Natalie E; Kulkarni, Prasad S; Shaligram, Umesh; Cotton, Mark F; Rentsch, Cyrill A; Eisele, Bernd; Grode, Leander; Kaufmann, Stefan H E

2017-01-01

The only licensed vaccine against tuberculosis (TB), bacille Calmette-Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes . Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔ ureC :: hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

A Preschool Obesity Treatment Clinical Trial: Reasons Primary Care Providers Declined Referrals.

PubMed

Robson, Shannon M; Bolling, Christopher; McCullough, Mary Beth; Stough, Cathleen Odar; Stark, Lori J

2016-10-01

To examine referral by primary care providers (PCPs) of preschool children with obesity (≥95th percentile for body mass index [BMI]) to a weight management intervention when offered through a randomized clinical trial (RCT), and identify reasons for not referring children. In phase I, 3 experts in obesity, psychology, and nutrition completed an open card sort and classified PCPs' reasons for declining referral into groups based on similarity of reasons. Categories were then defined and labeled. In phase II, 2 independent sorters placed each decline into 1 of the categories defined in phase I. PCPs referred 78% of eligible children to the RCT. Compared with children declined for referral, referred children had a significantly higher weight (48.4 lb vs 46.1 lb; P < .001) and BMI percentile (97.6 vs 97.0; P < .001). Eleven categories for decline were identified in phase I. In phase II, excellent reliability was obtained between each independent sorter and the phase I categories, and also between the 2 independent sorters (κ values, 0.72-1.0). The most common reason for declining was "family not a good fit" (23.6%), followed by "doesn't believe weight is a problem" (13.9%), "family would not be interested" (12%), and "doesn't believe measurement is accurate" (11.5%). Appropriately, exclusionary criteria of the RCT was a reason as well (11.8%). The availability of weight management for preschoolers through RCTs appeared to overcome barriers of resources, time, and credible treatment cited in previous studies. However, concerns about the family's response or interest in a weight management program remained barriers, as did PCPs' perceptions about obesity in young children. ClinicalTrials.gov:NCT01546727. Copyright © 2016 Elsevier Inc. All rights reserved.

Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study

PubMed Central

Nnoaham, Kelechi E.; Hummelshoj, Lone; Kennedy, Stephen H.; Jenkinson, Crispin; Zondervan, Krina T.

2012-01-01

Objective To generate and validate symptom-based models to predict endometriosis among symptomatic women prior to undergoing their first laparoscopy. Design Prospective, observational, two-phase study, in which women completed a 25-item questionnaire prior to surgery. Setting Nineteen hospitals in 13 countries. Patient(s) Symptomatic women (n = 1,396) scheduled for laparoscopy without a previous surgical diagnosis of endometriosis. Intervention(s) None. Main Outcome Measure(s) Sensitivity and specificity of endometriosis diagnosis predicted by symptoms and patient characteristics from optimal models developed using multiple logistic regression analyses in one data set (phase I), and independently validated in a second data set (phase II) by receiver operating characteristic (ROC) curve analysis. Result(s) Three hundred sixty (46.7%) women in phase I and 364 (58.2%) in phase II were diagnosed with endometriosis at laparoscopy. Menstrual dyschezia (pain on opening bowels) and a history of benign ovarian cysts most strongly predicted both any and stage III and IV endometriosis in both phases. Prediction of any-stage endometriosis, although improved by ultrasound scan evidence of cyst/nodules, was relatively poor (area under the curve [AUC] = 68.3). Stage III and IV disease was predicted with good accuracy (AUC = 84.9, sensitivity of 82.3% and specificity 75.8% at an optimal cut-off of 0.24). Conclusion(s) Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy. Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis. We invite other researchers to validate the key models in additional populations. PMID:22657249

Probing HeII Reionization at z>3.5 with Resolved HeII Lyman Alpha Forest Spectra

NASA Astrophysics Data System (ADS)

Worseck, Gabor

2017-08-01

The advent of GALEX and COS have revolutionized our view of HeII reionization, the final major phase transition of the intergalactic medium. COS spectra of the HeII Lyman alpha forest have confirmed with high confidence the high HeII transmission that signifies the completion of HeII reionization at z 2.7. However, the handful of z>3.5 quasars observed to date show a set of HeII transmission 'spikes' and larger regions with non-zero transmission that suggest HeII reionization was well underway by z=4. This is in striking conflict with predictions from state-of-the-art radiative transfer simulations of a HeII reionization driven by bright quasars. Explaining these measurements may require either faint quasars or more exotic sources of hard photons at z>4, with concomitant implications for HI reionization. However, many of the observed spikes are unresolved in G140L spectra and are significantly impacted by Poisson noise. Current data cannot reliably probe the ionization state of helium at z>3.5.We request 41 orbits to obtain science-grade G130M spectra of the two UV-brightest HeII-transmitting QSOs at z>3.5 to confirm and resolve their HeII transmission spikes as an unequivocal test of early HeII reionization. These spectra are complemented by recently obtained data from 8m telescopes: (1) Echelle spectra of the coeval HI Lya forest to map the underlying density field that modulates the HeII absorption, and (2) Our dedicated survey for foreground QSOs that may source the HeII transmission. Our recent HST programs revealed the only two viable targets to resolve the z>3.5 HeII Lyman alpha forest, and to conclusively solve this riddle.

Chesapeake Bay Low Freshwater Inflow Study. Phase II. MAP FOLIO. Biota Assessment.

DTIC Science & Technology

1982-05-01

conditions. These were: 1) Base Average -- average freshwater inflow conditions. by increased water consumption projected for the year 2020. 3) Base Drought...RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS. 1963- A TAI m - ii J May 1982 Chesapeake Bay Low Freshwater Inflow Study Phase II Biota Assessment Map...A PERIOD ZOVERED change was found to CIESAPEAKE BAY LOW FRESHWATER INFLOW STUDY FINAL BIOTA ASSESSMENT PHASE II: FINAL REPORT MAP FOLIO s PERFORMING

Effects of Combined Phase III and Phase II Cardiac Exercise Therapy for Middle-aged Male Patients with Acute Myocardial Infarction

PubMed Central

Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Huang, Chien-Hui

2013-01-01

[Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET. PMID:24396201

Supplementation of Dried Mealworm (Tenebrio molitor larva) on Growth Performance, Nutrient Digestibility and Blood Profiles in Weaning Pigs

PubMed Central

Jin, X. H.; Heo, P. S.; Hong, J. S.; Kim, N. J.; Kim, Y. Y.

2016-01-01

This experiment was conducted to investigate the effects of dried mealworm (Tenebrio molitor larva) on growth performance, nutrient digestibility and blood profiles in weaning pigs. A total of 120 weaning pigs (28±3 days and 8.04±0.08 kg of body weight) were allotted to one of five treatments, based on sex and body weight, in 6 replicates with 4 pigs per pen by a randomized complete block design. Supplementation level of dried mealworm was 0%, 1.5%, 3.0%, 4.5%, or 6.0% in experimental diet as treatment. Two phase feeding programs (phase I from 0 day to 14 day, phase II from 14 day to 35 day) were used in this experiment. All animals were allowed to access diet and water ad libitum. During phase I, increasing level of dried mealworm in diet linearly improved the body weight (p<0.01), average daily gain (ADG) (p<0.01) and average daily feed intake (ADFI) (p<0.01). During phase II, ADG also tended to increase linearly when pigs were fed higher level of dried mealworm (p = 0.08). In addition, increasing level of dried mealworm improved the ADG (p<0.01), ADFI (p<0.05) and tended to increase gain to feed ratio (p = 0.07) during the whole experimental period. As dried mealworm level was increased, nitrogen retention and digestibility of dry matter as well as crude protein were linearly increased (p = 0.05). In the results of blood profiles, decrease of blood urea nitrogen (linear, p = 0.05) and increase of insulin-like growth factor (linear, p = 0.03) were observed as dried mealworm was increased in diet during phase II. However, there were no significant differences in immunoglobulin A (IgA) and IgG concentration by addition of dried mealworm in the growth trial. Consequently, supplementation of dried mealworm up to 6% in weaning pigs’ diet improves growth performance and nutrient digestibility without any detrimental effect on immune responses. PMID:27282974

47 CFR 54.310 - Connect America Fund for Price Cap Territories-Phase II

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund for Price Cap Territories... Connect America Fund for Price Cap Territories—Phase II (a) Geographic areas eligible for support. Connect America Phase II support may be made available for census blocks or other areas identified as eligible by...

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Raman Frequencies Calculated from the Volume Data as a Function of Temperature at High Pressures for the Disordered Phase II of NH4I

NASA Astrophysics Data System (ADS)

Yurtseven, H.; Kavruk, D.

In this study, we calculate the Raman frequencies as a function of temperature for the fixed pressures of 706, 1080 and 6355 bars using the volume data for phase II of ammonium iodide. The Raman frequencies calculated here are for the translational optic ν5 TOM (125 cm-1) lattice mode that is located at the zone boundary (M point) of the Brillouin zone of phase II for NH4I. For this calculation the volume data obtained at zero pressure, is used through the mode Grüneisen parameter for the disordered phase II (β phase) which has the CsCl structure of NH4I. Our predicted frequencies of the ν5 TOM (125 cm-1) mode can be compared when the Raman data for this lattice mode is available at various temperatures for fixed pressures of 706, 1080 and 6355 bars in the disordered phase II of ammonium iodide.

Experience from operating germanium detectors in GERDA

NASA Astrophysics Data System (ADS)

Palioselitis, Dimitrios; GERDA Collaboration

2015-05-01

Phase I of the Germanium Detector Array (GERDA) experiment, searching for the neutrinoless double beta (0νββ) decay of 76Ge, was completed in September 2013. The most competitive half-life lower limit for the 0νββ decay of 76Ge was set (T-0ν1/2 > 2.1 · 1025 yr at 90% C.L.). GERDA operates bare Ge diodes immersed in liquid argon. During Phase I, mainly refurbished semi-coaxial high purity Ge detectors from previous experiments were used. The experience gained with handling and operating bare Ge diodes in liquid argon, as well as the stability and performance of the detectors during GERDA Phase I are presented. Thirty additional new enriched BEGe-type detectors were produced and will be used in Phase II. A subgroup of these detectors has already been used successfully in GERDA Phase I. The present paper gives an overview of the production chain of the new germanium detectors, the steps taken to minimise the exposure to cosmic radiation during manufacturing, and the first results of characterisation measurements in vacuum cryostats.

Reliability of a computer-based system for measuring visual performance skills.

PubMed

Erickson, Graham B; Citek, Karl; Cove, Michelle; Wilczek, Jennifer; Linster, Carolyn; Bjarnason, Brendon; Langemo, Nathan

2011-09-01

Athletes have demonstrated better visual abilities than nonathletes. A vision assessment for an athlete should include methods to evaluate the quality of visual performance skills in the most appropriate, accurate, and repeatable manner. This study determines the reliability of the visual performance measures assessed with a computer-based system, known as the Nike Sensory Station. One hundred twenty-five subjects (56 men, 69 women), age 18 to 30, completed Phase I of the study. Subjects attended 2 sessions, separated by at least 1 week, in which identical protocols were followed. Subjects completed the following assessments: Visual Clarity, Contrast Sensitivity, Depth Perception, Near-Far Quickness, Target Capture, Perception Span, Eye-Hand Coordination, Go/No Go, and Reaction Time. An additional 36 subjects (20 men, 16 women), age 22 to 35, completed Phase II of the study involving modifications to the equipment, instructions, and protocols from Phase I. Results show no significant change in performance over time on assessments of Visual Clarity, Contrast Sensitivity, Depth Perception, Target Capture, Perception Span, and Reaction Time. Performance did improve over time for Near-Far Quickness, Eye-Hand Coordination, and Go/No Go. The results of this study show that many of the Nike Sensory Station assessments show repeatability and no learning effect over time. The measures that did improve across sessions show an expected learning effect caused by the motor response characteristics being measured. Copyright © 2011 American Optometric Association. Published by Elsevier Inc. All rights reserved.

Testosterone metabolism in the estuarine mysid Neomysis integer (Crustacea; Mysidacea) following tributyltin exposure.

PubMed

Verslycke, Tim; Poelmans, Sofie; De Wasch, Katia; Vercauteren, Jordy; Devos, Christophe; Moens, Luc; Sandra, Patrick; De Brabander, Hubert F; Janssen, Colin R

2003-09-01

Current evidence suggests that the biocide tributyltin (TBT) causes the development of imposex, a state of pseudohermaphrodism in which females exhibit functional secondary male characteristics, by altering the biotransformation or elimination of testosterone. Imposex in gastropods following TBT exposure is the most complete example of the effects of an endocrine disrupter on marine invertebrates. Previous studies have demonstrated that the estuarine mysid Neomysis integer converts testosterone into multiple polar and nonpolar metabolites resulting from both phase I and phase II biotransformations. In this study, the effects of TBT chloride (TBTCl) on the phase I and II testosterone metabolism of N. integer were evaluated. The TBTCl was highly toxic to N. integer (96-h median lethal concentration [LC50] of 164 ng/L). To assess the effects on testosterone metabolism, mysids were exposed for 96 h to different concentrations of TBTCl (control, 10, 100, and 1,000 ng/L), and testosterone elimination as polar hydroxylated, nonpolar oxido-reduced, and glucose- and sulfate-conjugated metabolites was examined. The TBTCl differentially affected testosterone metabolism. The effect of TBTCl on phase I metabolism was unclear and has been shown to vary among species, likely depending on the inducibility or presence of certain P450 isozyme families. Reductase activity and metabolic androgenization were induced in the 10-ng/L treatment, whereas higher concentrations resulted in a reduction of sulfate conjugation. The exact mechanisms underlying TBT-induced imposex and alterations in the steroid metabolism need to be further elucidated.

Iodine Hall Thruster

NASA Technical Reports Server (NTRS)

Szabo, James

2015-01-01

Iodine enables dramatic mass and cost savings for lunar and Mars cargo missions, including Earth escape and near-Earth space maneuvers. The demonstrated throttling ability of iodine is important for a singular thruster that might be called upon to propel a spacecraft from Earth to Mars or Venus. The ability to throttle efficiently is even more important for missions beyond Mars. In the Phase I project, Busek Company, Inc., tested an existing Hall thruster, the BHT-8000, on iodine propellant. The thruster was fed by a high-flow iodine feed system and supported by an existing Busek hollow cathode flowing xenon gas. The Phase I propellant feed system was evolved from a previously demonstrated laboratory feed system. Throttling of the thruster between 2 and 11 kW at 200 to 600 V was demonstrated. Testing showed that the efficiency of iodine fueled BHT-8000 is the same as with xenon, with iodine delivering a slightly higher thrust-to-power (T/P) ratio. In Phase II, a complete iodine-fueled system was developed, including the thruster, hollow cathode, and iodine propellant feed system. The nominal power of the Phase II system is 8 kW; however, it can be deeply throttled as well as clustered to much higher power levels. The technology also can be scaled to greater than 100 kW per thruster to support megawatt-class missions. The target thruster efficiency for the full-scale system is 65 percent at high specific impulse (Isp) (approximately 3,000 s) and 60 percent at high thrust (Isp approximately 2,000 s).

Experiences of social harm and changes in sexual practices among volunteers who had completed a phase I/II HIV vaccine trial employing HIV-1 DNA priming and HIV-1 MVA boosting in Dar es Salaam, Tanzania.

PubMed

Tarimo, Edith A M; Munseri, Patricia; Aboud, Said; Bakari, Muhammad; Mhalu, Fred; Sandstrom, Eric

2014-01-01

Volunteers in phase I/II HIV vaccine trials are assumed to be at low risk of acquiring HIV infection and are expected to have normal lives in the community. However, during participation in the trials, volunteers may encounter social harm and changes in their sexual behaviours. The current study aimed to study persistence of social harm and changes in sexual practices over time among phase I/II HIV vaccine immunogenicity (HIVIS03) trial volunteers in Dar es Salaam, Tanzania. A descriptive prospective cohort study was conducted among 33 out of 60 volunteers of HIVIS03 trial in Dar es Salaam, Tanzania, who had received three HIV-1 DNA injections boosted with two HIV-1 MVA doses. A structured interview was administered to collect data. Analysis was carried out using SPSS and McNemars' chi-square (χ2) was used to test the association within-subjects. Participants reported experiencing negative comments from their colleagues about the trial; but such comments were less severe during the second follow up visits (χ2 = 8.72; P<0.001). Most of the comments were associated with discrimination (χ2 = 26.72; P<0.001), stigma (χ2 = 6.06; P<0.05), and mistrust towards the HIV vaccine trial (χ2 = 4.9; P<0.05). Having a regular sexual partner other than spouse or cohabitant declined over the two follow-up periods (χ2 = 4.45; P<0.05). Participants in the phase I/II HIV vaccine trial were likely to face negative comments from relatives and colleagues after the end of the trial, but those comments decreased over time. In this study, the inherent sexual practice of having extra sexual partners other than spouse declined over time. Therefore, prolonged counselling and support appears important to minimize risky sexual behaviour among volunteers after participation in HIV Vaccine trials.

The National Geographic Names Data Base: Phase II instructions

USGS Publications Warehouse

Orth, Donald J.; Payne, Roger L.

1987-01-01

not recorded on topographic maps be added. The systematic collection of names from other sources, including maps, charts, and texts, is termed Phase II. In addition, specific types of features not compiled during Phase I are encoded and added to the data base. Other names of importance to researchers and users, such as historical and variant names, are also included. The rules and procedures for Phase II research, compilation, and encoding are contained in this publication.

Mixed response and time-to-event endpoints for multistage single-arm phase II design.

PubMed

Lai, Xin; Zee, Benny Chung-Ying

2015-06-04

The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

A Fire Safety Certification System for Board and Care Operators and Staff. SBIR Phase II: Final Report.

ERIC Educational Resources Information Center

Walker, Bonnie L.

This report describes Phase II of a project which developed a system for delivering fire safety training to board and care providers who serve adults with developmental disabilities. Phase II focused on developing and pilot testing a "train the trainers" workshop for instructors and field testing the provider's workshop. Evaluation of…

Single-arm phase II trial design under parametric cure models.

PubMed

Wu, Jianrong

2015-01-01

The current practice of designing single-arm phase II survival trials is limited under the exponential model. Trial design under the exponential model may not be appropriate when a portion of patients are cured. There is no literature available for designing single-arm phase II trials under the parametric cure model. In this paper, a test statistic is proposed, and a sample size formula is derived for designing single-arm phase II trials under a class of parametric cure models. Extensive simulations showed that the proposed test and sample size formula perform very well under different scenarios. Copyright © 2015 John Wiley & Sons, Ltd.

Applied Meteorology Unit (AMU) Quarterly Report Third Quarter FY-08

NASA Technical Reports Server (NTRS)

Bauman, William; Crawford, Winifred; Barrett, Joe; Watson, Leela; Dreher, Joseph

2008-01-01

This report summarizes the Applied Meteorology Unit (AMU) activities for the third quarter of Fiscal Year 2008 (April - June 2008). Tasks reported on are: Peak Wind Tool for User Launch Commit Criteria (LCC), Anvil Forecast Tool in AWIPS Phase II, Completion of the Edward Air Force Base (EAFB) Statistical Guidance Wind Tool, Volume Averaged Height Integ rated Radar Reflectivity (VAHIRR), Impact of Local Sensors, Radar Scan Strategies for the PAFB WSR-74C Replacement, VAHIRR Cost Benefit Analysis, and WRF Wind Sensitivity Study at Edwards Air Force Base

Robotics Offer Newfound Surgical Capabilities

NASA Technical Reports Server (NTRS)

2008-01-01

Barrett Technology Inc., of Cambridge, Massachusetts, completed three Phase II Small Business Innovation Research (SBIR) contracts with Johnson Space Center, during which the company developed and commercialized three core technologies: a robotic arm, a hand that functions atop the arm, and a motor driver to operate the robotics. Among many industry uses, recently, an adaptation of the arm has been cleared by the U.S. Food and Drug Administration (FDA) for use in a minimally invasive knee surgery procedure, where its precision control makes it ideal for inserting a very small implant.

Client satisfaction with the nutrition education component of the California WIC program.

PubMed

Nestor, B; McKenzie, J; Hasan, N; AbuSabha, R; Achterberg, C

2001-01-01

Past evaluation research has documented improved nutritional outcomes resulting from participation in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). However, these evaluations have not examined the program from the clients' perspective, nor have they examined the independent effect of the nutrition education component. The purpose of this study was to quantitatively and qualitatively examine client satisfaction with the nutrition education component of the California WIC program. The methodology consisted of two phases. During phase I of the study (the quantitative component), participants completed Client Satisfaction Surveys immediately following attendance of one nutrition class. During phase II (the qualitative component), four focus groups were conducted. All subjects were participants in the California WIC program. Client Satisfaction Surveys were completed by 2138 participants, and the focus groups included 29 participants. Results from both phases of the study indicated that client satisfaction with the nutrition education component of the California WIC program was high. Between 80% and 95% of participants responded positively to five satisfaction questions, and focus group participants unanimously agreed that the nutrition education was an essential component of the program. Hispanic participants were more likely than non-Hispanic Caucasians, Asians, or African Americans to respond positively to three of the five satisfaction questions. For two of the questions, the frequency of positive responses increased as age increased and decreased as education level increased. A small segment of clients reported some dissatisfaction by responding negatively to one or more of the satisfaction questions (4% to 20% of respondents). Some suggestions for improvement were made by survey respondents. Identification of some WIC participants who are not completely satisfied with the nutrition education that they have received, paired with differences in satisfaction across demographic variables, suggests the need for a personalized approach to WIC nutrition education.

The development of coal-based technologies for Department of Defense facilities. Volume 1, Technical report. Semiannual technical progress report, September 28, 1994--March 27, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, B.G.; Bartley, D.A.; Hatcher, P.

1996-10-15

This program is being conducted as a cooperative agreement between the Consortium for Coal Water Mixture Technology and the U.S. Department of Energy. Activities this reporting period are summarized by phase. Phase I is nearly completed. During this reporting period, coal beneficiation/preparation studies, engineering designs and economics for retrofitting the Crane, Indiana boiler to fire coal-based fuels, and a 1,000-hour demonstration of dry, micronized coal were completed. In addition, a demonstration-scale micronized-coal water mixture (MCWM) preparation circuit was constructed and a 1,000-hour demonstration firing MCWM began. Work in Phase II focused on emissions reductions, coal beneficiation/preparation studies, and economic analysesmore » of coal use. Emissions reductions investigations involved literature surveys of NO{sub x}, SO{sub 2}, trace metals, volatile organic compounds, and fine particulate matter capture. In addition, vendors and engineering firms were contacted to identify the appropriate emissions technologies for the installation of commercial NO{sub x} and SO{sub 2} removal systems on the demonstration boiler. Information from the literature surveys and engineering firms will be used to identify, design, and install a control system(s). Work continued on the refinement and optimization of coal grinding and MCWM preparation procedures, and on the development of advanced processes for beneficiating high ash, high sulfur coals. Work also continued on determining the basic cost estimation of boiler retrofits, and evaluating environmental, regulatory, and regional economic impacts. In addition, the feasibility of technology adoption, and the public`s perception of the benefits and costs of coal usage was studied. A coal market analysis was completed. Work in Phase III focused on coal preparation studies, emissions reductions and economic analyses of coal use.« less

The coordination structure of the extracted copper(II) complex with a synergistic mixture containing dinonylnaphthalene sulfonic acid and n-hexyl 3-pyridinecarboxylate ester

NASA Astrophysics Data System (ADS)

Zhu, Shan; Hu, Huiping; Hu, Jiugang; Li, Jiyuan; Hu, Fang; Wang, Yongxi

2017-09-01

In continuation of our interest in the coordination structure of the nickel(II) complex with dinonylnaphthalene sulfonic acid (HDNNS) and 2-ethylhexyl 4-pyridinecarboxylate ester (4PC), it was observed that the coordination sphere was completed by the coordination of two N atoms of pyridine rings in ligands 4PC and four water molecules while no direct interaction between Ni(II) and deprotonated HDNNS was observed. To investigate whether the coordination structure of nickel(II) with the synergistic mixture containing HDNNS and 4PC predominates or not in the copper(II) complex with the synergistic mixtures containing HDNNS and pyridinecarboxylate esters, a copper(II) synergist complex with n-hexyl 3-pyridinecarboxylate ester (L) and naphthalene-2-sulfonic acid (HNS, the short chain analogue of HDNNS), was prepared and studied by X-ray single crystal diffraction, elemental analyses and thermo gravimetric analysis (TGA), respectively. It was shown that the composition of the copper(II) synergist complex was [Cu(H2O)2(L)2(NS)2] and formed a trans-form distorted octahedral coordination structure. Two oxygen atoms of the two coordinated water molecules and two N atoms of the pyridine rings in the ligands L defined the basal plane while two O atoms from two sulfonate anions of the deprotonated HNS ligands occupied the apical positions by direct coordination with Cu(II), which was distinguished from the coordination structure of the nickel(II) synergist complex as reported in our previous work. In the crystal lattice, neighboring molecules [Cu(H2O)2L2(NS)2] were linked through the intermolecular hydrogen bonds between the hydrogen atoms of the coordinated water molecules and the oxygen atoms of the sulfonate anions in the copper(II) synergist complex to form a 2D plane. In order to bridge the gap between the solid state structure of the copper(II) synergist complex and the solution structure of the extracted copper(II) complex with the actual synergistic mixture containing L and HDNNS in the non-polar organic phase, the structures of the two copper(II) complexes were further investigated by Fourier transform infrared spectroscopy (FT-IR) and electrospray ionization mass spectrometry (ESI-MS), and the results indicated that the extracted copper(II) complex in the non-polar organic phase might possess a similar coordination structure as the copper(II) synergist complex.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Starcher, Autumn N.; Elzinga, Evert J.; Sparks, Donald L.

Previous research demonstrated the formation of single divalent metal (Co, Ni, and ZnAl) and mixed divalent metal (NiZnAl) layered double hydroxide (LDH) phases from reactions of the divalent metal with Al-bearing substrates and soils in both laboratory experiments and in the natural environment. Recently Fe(II)-Al-LDH phases have been found in laboratory batch reaction studies, and although they have yet to be found in the natural environment. Potential locations of Fe(II)-Al-LDH phases in nature include areas with suboxic and anoxic conditions. Because these areas can be environments of significant contaminant accumulation, it is important to understand the possible interactions and impactsmore » of contaminant elements on LDH phase formation. One such contaminant, Zn, can also form as an LDH and has been found to form as a mixed divalent layered hydroxide phase. To understand how Zn impacts the formation of Fe(II)-Al-LDH phase formation and kinetics, 3 mM or 0.8 mM Fe(II) and 0.8 mM Zn were batch reacted with either 10 g/L pyrophyllite or 7.5 g/L γ-Al2O3 for up to three months under anoxic conditions. Aqueous samples were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) and solid samples were analyzed with X-ray absorption spectroscopy (XAS). Shell-by-shell fits of Fe(II) and co-sorption samples with pyrophyllite show the formation of a mixed divalent metal (Fe(II)-Zn-Al) layered hydroxide phase, while Fe(II) and Zn co-sorption samples with γ-Al2O3 produce Fe(II)-Al-LDH phases and Zn in inner-sphere complexation with the γ-Al2O3. This study demonstrates the formation of a mixed divalent metal layered hydroxide and further iterates the importance of sorbent reactivity on LDH phase formation.« less

Final Report for PV Incubator Subcontract No. NAT-0-99013-01: June 14, 2010 - March 2, 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosal, K.

2012-04-01

The goal of the subcontract is to scale up Semprius' novel micro-cell based modules to an annualized rate of 500 kW of receivers and 10 kW of modules, in support of the DOE 2020 Sunshot Initiative goals. The statement of work (SOW) was broken up into two Phases. Phase I was directed towards process development efforts towards addressing fundamental manufacturing metrics such as yield, die per wafer, automation and throughput. Phase II objectives are to scale to an annualized production rate of 500 kW of receivers and 10 kW of modules, while improving cell efficiency, module efficiency and transfer yield.more » Semprius has met all the technical milestones and deliverables for the contract. All subtasks were completed earlier than expected and the results exceeded the technical targets. In particular, 3J cell efficiency of 41.2% exceeded the target of 38%, module efficiency of 28.3% exceeded the target of 28% and transfer yield of 96.4% exceeds the target of 95%, with all tasks completed well ahead of schedule. Also, devices fabricated from 1st use GaAs substrates and substrates with two re-uses have been shown to be identical.« less

Electronic monitoring and voice prompts improve hand hygiene and decrease nosocomial infections in an intermediate care unit.

PubMed

Swoboda, Sandra M; Earsing, Karen; Strauss, Kevin; Lane, Stephen; Lipsett, Pamela A

2004-02-01

To determine whether electronic monitoring of hand hygiene and voice prompts can improve hand hygiene and decrease nosocomial infection rates in a surgical intermediate care unit. Three-phase quasi-experimental design. Phase I was electronic monitoring and direct observation; phase II was electronic monitoring and computerized voice prompts for failure to perform hand hygiene on room exit; and phase III was electronic monitoring only. Nine-room, 14-bed intermediate care unit in a university, tertiary-care institution. All patient rooms, utility room, and staff lavatory were monitored electronically. All healthcare personnel including physicians, nurses, nursing support personnel, ancillary staff, all visitors and family members, and any other personnel interacting with patients on the intermediate care unit. All patients with an intermediate care unit length of stay >48 hrs were followed for nosocomial infection. Electronic monitoring during all phases, computerized voice prompts during phase II only. We evaluated a total of 283,488 electronically monitored entries into a patient room with 251,526 exits for 420 days (10,080 hrs and 3,549 patient days). Compared with phase I, hand hygiene compliance in patient rooms improved 37% during phase II (odds ratio, 1.38; 95% confidence interval, 1.04-1.83) and 41% in phase III (odds ratio, 1.41; 95% confidence interval, 1.07-1.84). When adjusting for patient admissions during each phase, point estimates of nosocomial infections decreased by 22% during phase II and 48% during phase III; when adjusting for patient days, the number of infections decreased by 10% during phase II and 40% during phase III. Although the overall rate of nosocomial infections significantly decreased when combining phases II and III, the association between nosocomial infection and individual phase was not significant. Electronic monitoring provided effective ongoing feedback about hand hygiene compliance. During both the voice prompt phase and post-intervention phase, hand hygiene compliance and nosocomial infection rates improved suggesting that ongoing monitoring and feedback had both a short-term and, perhaps, a longer-term effect.

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

PubMed

Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

2015-06-01

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year relapse-free survival rate was 81%. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

A stereochemical examination of the equine metabolism of 17alpha-methyltestosterone.

PubMed

McKinney, Andrew R; Suann, Craig J; Stenhouse, Allen M

2007-01-09

An investigation was conducted into the stereochemistry of the equine urinary metabolites of 17alpha-methyltestosterone observed after oral administration. Standards of the complete range of C3/C5/C16 stereoisomeric 17alpha-methylandrostane-3,17beta-diols, 17alpha-methylandrostane-3,16,17beta-triols and 17alpha-hydroxymethylandrostane-3,17beta-diols were purchased or synthesised, and were used to unequivocally identify the absolute structures of the metabolites. Phase I metabolism was found to involve combinations of Delta(4)-3-ketone reduction with both 5alpha,3beta- and 5beta,3alpha-stereochemistry, hydroxylation at C16 with both 16alpha- and 16beta-stereochemistry and hydroxylation of the 17alpha-methyl substituent. Phase II metabolism involved mainly sulfation with a lesser degree of beta-glucuronidation.

Phased Retrofits in Existing Homes in Florida Phase II: Shallow Plus Retrofits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, K.; Parker, D.; Martin, E.

Originally published in February 2016, this revision contains an added section called 'Evaluation of Complete Central System Replacement with Inverter-Driven Heat Pump,' which presents the designs and energy savings evaluations of two different schemes wherein inverter-driven systems replaced a home's existing central system. Analyses for three additional retrofit measures were bolstered by longer-term data; these are described in the sections on supplemental mini-split heat pumps (MSHPs), smart thermostats, and heat pump clothes dryers. The sections on supplemental MSHPs and smart thermostats were also enhanced with larger sample sizes and projections of weather-normalized annual energy savings. Finally, peak system hour energymore » demand-reduction predictions are provided for all retrofit measures where meaningful impacts could be drawn.« less

Phased Retrofits in Existing Homes in Florida Phase II: Shallow Plus Retrofits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, K.; Parker, D.; Martin, E.

Originally published in February 2016, this revision contains an added section called 'Evaluation of Complete Central System Replacement with Inverter-Driven Heat Pump,' which presents the designs and energy savings evaluations of two different schemes wherein inverter-driven systems replaced a home’s existing central system. Analyses for three additional retrofit measures were bolstered by longer-term data; these are described in the sections on supplemental mini-split heat pumps (MSHPs), smart thermostats, and heat pump clothes dryers. The sections on supplemental MSHPs and smart thermostats were also enhanced with larger sample sizes and projections of weather-normalized annual energy savings. Finally, peak system hour energymore » demand-reduction predictions are provided for all retrofit measures where meaningful impacts could be drawn.« less

The current status of neoadjuvant therapy for esophageal cancer.

PubMed

Lin, Daniel; Leichman, Lawrence

2014-01-01

Through the contribution of a very large number of single-arm phase II trials and many less randomized phase III trials, the standard of care for locally advanced esophageal cancer has evolved to either combination chemotherapy plus radiation or combination chemotherapy. In this review, we focus on the key findings of these studies and selected meta-analyses that have led to this evolution. We note differences in outcomes for adenocarcinomas of the esophagus when compared to squamous cell esophageal cancers. Despite progress in developing a consensus for therapy, the outcome for patients with locally advanced remains poor. We complete the review by noting newer areas of investigation seeking to provide targeted and more personalized therapy to patients with esophageal cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

CMIF ECLS system test findings

NASA Technical Reports Server (NTRS)

Schunk, Richard G.; Carrasquillo, Robyn L.; Ogle, Kathyrn Y.; Wieland, Paul O.; Bagdigian, Robert M.

1989-01-01

During 1987 three Space Station integrated Environmental Control and Life Support System (ECLSS) tests were conducted at the Marshall Space Flight Center (MSFC) Core Module Integration Facility (CMIF) as part of the MSFC ECLSS Phase II test program. The three tests ranged in duration from 50 to 150 hours and were conducted inside of the CMIF module simulator. The Phase II partial integrated system test configuration consisted of four regenerative air revitalization subsystems and one regenerative water reclamation subsystem. This paper contains a discussion of results and lessons learned from the Phase II test program. The design of the Phase II test configuration and improvements made throughout the program are detailed. Future plans for the MSFC CMIF test program are provided, including an overview of planned improvements for the Phase III program.

Investing in Our Nation's Youth. National Youth Anti-Drug Media Campaign: Phase II (Final Report).

ERIC Educational Resources Information Center

Office of National Drug Control Policy, Washington, DC.

This publication presents the findings from an evaluation of Phase II of the National Youth Anti-Drug Media Campaign. The number one goal of the campaign was to educate youth to reject illegal drugs. This report evaluates Phase II and focuses on the effect of paid television advertising on awareness of anti-drug messages among youth, teens, and…

Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II-III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Ken, E-mail: kenkato@ncc.go.jp; Muro, Kei; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi

Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m{sup 2}/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m{sup 2}) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-weekmore » break. Responders received two courses of 5-FU (800 mg/m{sup 2}/day) on Days 1-5 and CDDP (80 mg/m{sup 2}) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46 (62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity.« less

Generation of phase II in vitro metabolites using homogenized horse liver.

PubMed

Wong, Jenny K Y; Chan, George H M; Leung, David K K; Tang, Francis P W; Wan, Terence S M

2016-02-01

The successful use of homogenized horse liver for the generation of phase I in vitro metabolites has been previously reported by the authors' laboratory. Prior to the use of homogenized liver, the authors' laboratory had been using mainly horse liver microsomes for carrying out equine in vitro metabolism studies. Homogenized horse liver has shown significant advantages over liver microsomes for in vitro metabolism studies as the procedures are much quicker and have higher capability for generating more in vitro metabolites. In this study, the use of homogenized liver has been extended to the generation of phase II in vitro metabolites (glucuronide and/or sulfate conjugates) using 17β-estradiol, morphine, and boldenone undecylenate as model substrates. It was observed that phase II metabolites could also be generated even without the addition of cofactors. To the authors' knowledge, this is the first report of the successful use of homogenized horse liver for the generation of phase II metabolites. It also demonstrates the ease with which both phase I and phase II metabolites can now be generated in vitro simply by using homogenized liver without the need for ultracentrifuges or tedious preparation steps. Copyright © 2015 John Wiley & Sons, Ltd.

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

PubMed

Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

2018-02-01

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

Atomic data and spectral analysis of carbon, nitrogen, oxygen and silicon ions observed with the International Ultraviolet Explorer

NASA Technical Reports Server (NTRS)

Pradhan, Anil K.

1992-01-01

According to the plan presented in the original proposal we have now completed most of the atomic calculations involving collision strengths and rate coefficients for electron impact excitation of C II, N III, and O IV ions. These have been reported in the first two publications appended with this report. We have now moved into the applications phase of the project with the new data being used to analyze the International Ultraviolet Explorer (IUE) observations of a variety of objects, as described in the third publication recently submitted (also appended). The analysis and interpretation of archival data will continue well into the next year with several collaborators that the PI and Co-PI are involved with. In addition, the atomic calculations on Si II have been started.

Phenotypic variation of Pseudomonas brassicacearum as a plant root-colonization strategy.

PubMed

Achouak, Wafa; Conrod, Sandrine; Cohen, Valérie; Heulin, Thierry

2004-08-01

Pseudomonas brassicacearum was isolated as a major root-colonizing population from Arabidopsis thaliana. The strain NFM421 of P. brassicacearum undergoes phenotypic variation during A. thaliana and Brassica napus root colonization in vitro as well as in soil, resulting in different colony appearance on agar surfaces. Bacteria forming translucent colonies (phase II cells) essentially were localized at the surface of young roots and root tips, whereas wild-type cells (phase I cells) were localized at the basal part of roots. The ability of phase II cells to spread and colonize new sites on root surface correlates with over-production of flagellin as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of surface proteins and microsequencing. Moreover, phase II cells showed a higher ability to swim and to swarm on semisolid agar medium. Phase I and phase II cells of P. brassicacearum NFM421 were tagged genetically with green fluorescent protein and red fluorescent protein. Confocal scanning laser microscopy was used to localize phase II cells on secondary roots and root tips of A. thaliana, whereas phase I cells essentially were localized at the basal part of roots. These experiments were conducted in vitro and in soil. Phenotypic variation on plant roots is likely to be a colonization strategy that may explain the high colonization power of P. brassicacearum.

Probability of success for phase III after exploratory biomarker analysis in phase II.

PubMed

Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

2017-05-01

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

An Accurate Measurement of the IGM HeII Lyman Alpha Forest toward a Newly Discovered UV-bright Quasar at z>3.5

NASA Astrophysics Data System (ADS)

Worseck, Gabor

2016-10-01

The advent of GALEX and COS have revolutionized our view of HeII reionization, the final major phase transition of the intergalactic medium. COS spectra of the HeII Lyman alpha forest have confirmed with high confidence the high HeII transmission that signifies the completion of HeII reionization at z 2.7. However, the handful of z>3.5 quasars observed to date show a set of HeII transmission 'spikes' and larger regions with non-zero transmission that suggest HeII reionization was well underway by z=4. This is in striking conflict with predictions from state-of-the-art radiative transfer simulations of a HeII reionization driven by bright quasars. Explaining these measurements may require either faint quasars or more exotic sources of hard photons at z>4, with concomitant implications for HI reionization. We propose here to observe J2354-2033, an FUV-bright quasar at z=3.786 that we recently discovered in a dedicated survey for likely HeII-transmitting quasars. With this COS/G140L spectrum, we would confirm that the quasar is valuable for studies of the HeII Lyman alpha forest by identifying possible interloping low-z HI absorbers, provide accurate measurements of the IGM HeII opacity, and provide only the third z>3.5 sightline that would allow for high-resolution G130M spectroscopy before the end of HST's mission. The proposed observations would mark only the fourth observation of the HeII Lyman alpha forest at z>3.7 and the source would be the 2nd-brightest known on the sky at these redshifts.

Spiral chain structure of high pressure selenium-II{sup '} and sulfur-II from powder x-ray diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujihisa, Hiroshi; Yamawaki, Hiroshi; Sakashita, Mami

2004-10-01

The structure of high pressure phases, selenium-II{sup '} (Se-II{sup '}) and sulfur-II (S-II), for {alpha}-Se{sub 8} (monoclinic Se-I) and {alpha}-S{sub 8} (orthorhombic S-I) was studied by powder x-ray diffraction experiments. Se-II{sup '} and S-II were found to be isostructural and to belong to the tetragonal space group I4{sub 1}/acd, which is made up of 16 atoms in the unit cell. The structure consisted of unique spiral chains with both 4{sub 1} and 4{sub 3} screws. The results confirmed that the structure sequence of the pressure-induced phase transitions for the group VIb elements depended on the initial molecular form. The chemicalmore » bonds of the phases are also discussed from the interatomic distances that were obtained.« less

Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

PubMed

Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

1998-02-01

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

Procyanidins from wild grape (Vitis amurensis) seeds regulate ARE-mediated enzyme expression via Nrf2 coupled with p38 and PI3K/Akt pathway in HepG2 cells.

PubMed

Bak, Min-Ji; Jun, Mira; Jeong, Woo-Sik

2012-01-01

Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1-F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway.

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer.

PubMed

Kasahara, Kazuo; Kimura, Hideharu; Shibata, Kazuhiko; Araya, Tomoyuki; Sone, Takashi; Oribe, Yoshitaka; Furusho, Shiho; Kita, Toshiyuki; Shirasaki, Hiroki; Oribe, Yoshitaka; Yoshimi, Yuzo; Ueda, Akihito; Tachibana, Hideki; Shintani, Hiromoto; Mizuguchi, Masayuki; Nishi, Kohichi; Fujimura, Masaki; Nakao, Shinji

2006-01-01

The aim of this phase II study was to evaluate the efficacy of combination chemotherapy consisting of docetaxel and carboplatin in patients with inoperable non-small cell lung cancer (NSCLC). For this multicenter phase II study, the eligibility criteria included histologically or cytologically proven inoperable NSCLC, measurable lesions, Eastern Cooperative Oncology Group performance status (PS) 0-2, adequate organ and bone marrow functions, and written informed consent. Patients received 60 mg/m2 of docetaxel and carboplatin (target AUC 5.5) on day 1 every 3 weeks until disease progression. The primary end-point of this study was response rate and the secondary end-points were toxicities, time to progression and overall survival. A total of 40 patients were enrolled and 39 patients were eligible. A complete response and partial response were observed in 1 and 13 patients, respectively. An objective response rate was 35.9% (95% confidential interval [CI] 20.8-51.0%). The median time to progression was 5.2 months and the median overall survival was 12.0 months. The 1- and 2-year survival rates were 53.8% and 25.1%, respectively. The major toxicities were leukocytopenia and neutropenia. Grade 3 or 4 thrombocytopenia was rare and non-hematological toxicities were generally mild. Grade 3 non-hematological toxicities were observed in 6 patients (2 with nausea and vomiting, 1 with diarrhea, 1 with elevated transaminase levels, 1 with allergic reaction and 1 with edema). No grade 4 non-hematological toxicities were observed. Docetaxel and carboplatin combination chemotherapy was well tolerated and active in Japanese patients with advanced or metastatic NSCLC.

Increased photosystem II stability promotes H2 production in sulfur-deprived Chlamydomonas reinhardtii

PubMed Central

Volgusheva, Alena; Styring, Stenbjörn; Mamedov, Fikret

2013-01-01

Photobiological H2 production is an attractive option for renewable solar fuels. Sulfur-deprived cells of Chlamydomonas reinhardtii have been shown to produce hydrogen with the highest efficiency among photobiological systems. We have investigated the photosynthetic reactions during sulfur deprivation and H2 production in the wild-type and state transition mutant 6 (Stm6) mutant of Chlamydomonas reinhardtii. The incubation period (130 h) was dissected into different phases, and changes in the amount and functional status of photosystem II (PSII) were investigated in vivo by electron paramagnetic resonance spectroscopy and variable fluorescence measurements. In the wild type it was found that the amount of PSII is decreased to 25% of the original level; the electron transport from PSII was completely blocked during the anaerobic phase preceding H2 formation. This block was released during the H2 production phase, indicating that the hydrogenase withdraws electrons from the plastoquinone pool. This partly removes the block in PSII electron transport, thereby permitting electron flow from water oxidation to hydrogenase. In the Stm6 mutant, which has higher respiration and H2 evolution than the wild type, PSII was analogously but much less affected. The addition of the PSII inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea revealed that ∼80% of the H2 production was inhibited in both strains. We conclude that (i) at least in the earlier stages, most of the electrons delivered to the hydrogenase originate from water oxidation by PSII, (ii) a faster onset of anaerobiosis preserves PSII from irreversible photoinhibition, and (iii) mutants with enhanced respiratory activity should be considered for better photobiological H2 production. PMID:23589846

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

A Phase II Safety and Efficacy Study of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Patients With Metastatic Urothelial Cancer

PubMed Central

Pili, Roberto; Qin, Rui; Flynn, P.J.; Picus, Joel; Millward, Michael; Ho, Wing Ming; Pitot, Henry; Tan, Winston; Miles, Kiersten M.; Erlichman, Charles; Vaishampayan, Ulka

2013-01-01

Vascular endothelial growth factor (VEGF) is expressed in human bladder tumors. A phase II study was conducted to assess the VEGF inhibitor pazopanib in patients with metastatic, urothelial carcinoma. Nineteen patients with one prior systemic therapy were enrolled. No objective responses were observed and median progression-free survival was 1.9 months. The role of anti-VEGF therapies in urothelial carcinoma remains to be determined. Background Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma. Methods Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle. Results Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed. Conclusions Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. PMID:23891158

A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.

PubMed

Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G

2014-06-01

Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

Phase transition and chemical decomposition of hydrogen peroxide and its water mixtures under high pressures.

PubMed

Chen, Jing-Yin; Kim, Minseob; Yoo, Choong-Shik; Dattelbaum, Dana M; Sheffield, Stephen

2010-06-07

We have studied the pressure-induced phase transition and chemical decomposition of hydrogen peroxide and its mixtures with water to 50 GPa, using confocal micro-Raman and synchrotron x-ray diffractions. The x-ray results indicate that pure hydrogen peroxide crystallizes into a tetragonal structure (P4(1)2(1)2), the same structure previously found in 82.7% H(2)O(2) at high pressures and in pure H(2)O(2) at low temperatures. The tetragonal phase (H(2)O(2)-I) is stable to 15 GPa, above which transforms into an orthorhombic structure (H(2)O(2)-II) over a relatively large pressure range between 13 and 18 GPa. Inferring from the splitting of the nu(s)(O-O) stretching mode, the phase I-to-II transition pressure decreases in diluted H(2)O(2) to around 7 GPa for the 41.7% H(2)O(2) and 3 GPa for the 9.5%. Above 18 GPa H(2)O(2)-II gradually decomposes to a mixture of H(2)O and O(2), which completes at around 40 GPa for pure and 45 GPa for the 9.5% H(2)O(2). Upon pressure unloading, H(2)O(2) also decomposes to H(2)O and O(2) mixtures across the melts, occurring at 2.5 GPa for pure and 1.5 GPa for the 9.5% mixture. At H(2)O(2) concentrations below 20%, decomposed mixtures form oxygen hydrate clathrates at around 0.8 GPa--just after H(2)O melts. The compression data of pure H(2)O(2) and the stability data of the mixtures seem to indicate that the high-pressure decomposition is likely due to the pressure-induced densification, whereas the low-pressure decomposition is related to the heterogeneous nucleation process associated with H(2)O(2) melting.

TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: Distinct role of TNF receptor subtype 1 and 2

PubMed Central

Zhang, Ling; Berta, Temugin; Xu, Zhen-Zhong; Liu, Tong; Park, Jong Yeon; Ji, Ru-Rong

2010-01-01

Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine. It is generally believed that TNF-α exerts its effects primarily via TNF receptor subtype-1 (TNFR1). We investigated distinct role of TNFR1 and TNFR2 in spinal cord synaptic transmission and inflammatory pain. Compared to wild-type (WT) mice, TNFR1 and TNFR2 knockout (KO) mice exhibited normal heat sensitivity and unaltered excitatory synaptic transmission in the spinal cord, as revealed by spontaneous excitatory postsynaptic currents (sEPSCs) in lamina II neurons of spinal cord slices. However, heat hyperalgesia after intrathecal TNF-α and the second-phase spontaneous pain in the formalin test were reduced in both TNFR1- and TNFR2-KO mice. In particular, heat hyperalgesia after intraplantar injection of complete Freund's adjuvant (CFA) was decreased in the early phase in TNFR2-KO mice but reduced in both early and later phase in TNFR1-KO mice. Consistently, CFA elicited a transient increase of TNFR2 mRNA levels in the spinal cord on day 1. Notably, TNF-α evoked a drastic increase in sEPSC frequency in lamina II neurons, which was abolished in TNFR1-KO mice and reduced in TNFR2-KO mice. TNF-α also increased NMDA currents in lamina II neurons, and this increase was abolished in TNFR1-KO mice but retained in TNFR2-KO mice. Finally, intrathecal injection of the NMDA receptor antagonist MK-801 prevented heat hyperalgesia elicited by intrathecal TNF-α. Our findings support a central role of TNF-α in regulating synaptic plasticity (central sensitization) and inflammatory pain via both TNFR1 and TNFR2. Our data also uncover a unique role of TNFR2 in mediating early-phase inflammatory pain. PMID:21159431

Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma.

PubMed

Hashmi, Mehmood H; Van Veldhuizen, Peter J

2010-05-01

In advanced renal cell cancer and malignant melanoma, the current FDA approved immune modulators, such as IL-2, are the only agents which provide a durable complete remission. These responses, however, occur in < 10% of treated patients and their applicability is limited to selected patients because of their toxicity. The identification of new immunotherapeutic agents with an improved response rate and toxicity profile would represent a significant advancement in the treatment of these malignancies. This is a comprehensive review of IL-21 including its pharmacology and current developmental status. A literature review was performed using all PubMed listed publications involving IL-21, including original research articles, reviews and abstracts. It also includes a review of current ongoing trials and information from the official product website. Recombinant IL-21 (rIL-21) is a new immune modulator currently undergoing Phase I and II testing. It is a cytokine with a four helix structure that has structural and sequence homology to IL-2 and -15, but also possesses many unique biological properties. In this review, we evaluate the development, pharmacologic properties, safety profile and current clinical efficacy of rIL-21. rIL-21 has an acceptable safety profile and encouraging single agent activity in early phase renal cell carcinoma and melanoma clinical trials.

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing’s sarcoma

PubMed Central

Dutton, P; Love, SB; Billingham, L; Hassan, AB

2016-01-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency. PMID:27587590

The Origins of [C ii] Emission in Local Star-forming Galaxies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croxall, K. V.; Smith, J. D.; Pellegrini, E.

The [C ii] 158 μ m fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [C ii] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [C ii] emission remains unclear because C{sup +} can be found in multiple phases of the interstellar medium. Here we measure the fractions of [C ii] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [N ii] 205 μ m fine-structuremore » line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [C ii]/[N ii] 122 μ m. Using the FIR [C ii] and [N ii] emission detected by the KINGFISH (Key Insights on Nearby Galaxies: a Far- Infrared Survey with Herschel ) and Beyond the Peak Herschel programs, we show that 60%–80% of [C ii] emission originates from neutral gas. We find that the fraction of [C ii] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and has a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [C ii] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are provided.« less

Alternate Reductant Cold Cap Evaluation Furnace Phase II Testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, F. C.; Stone, M. E.; Miller, D. H.

2014-09-03

Savannah River Remediation (SRR) conducted a Systems Engineering Evaluation (SEE) to determine the optimum alternate reductant flowsheet for the Defense Waste Processing Facility (DWPF). Specifically, two proposed flowsheets (nitric–formic–glycolic and nitric–formic–sugar) were evaluated based upon results from preliminary testing. Comparison of the two flowsheets among evaluation criteria indicated a preference towards the nitric–formic–glycolic flowsheet. Further research and development of this flowsheet eliminated the formic acid, and as a result, the nitric–glycolic flowsheet was recommended for further testing. Based on the development of a roadmap for the nitric–glycolic acid flowsheet, Waste Solidification Engineering (WS-E) issued a Technical Task Request (TTR) tomore » address flammability issues that may impact the implementation of this flowsheet. Melter testing was requested in order to define the DWPF flammability envelope for the nitric-glycolic acid flowsheet. The Savannah River National Laboratory (SRNL) Cold Cap Evaluation Furnace (CEF), a 1/12 th scale DWPF melter, was selected by the SRR Alternate Reductant project team as the melter platform for this testing. The overall scope was divided into the following sub-tasks as discussed in the Task Technical and Quality Assurance Plan (TTQAP): Phase I - A nitric–formic acid flowsheet melter test (unbubbled) to baseline the CEF cold cap and vapor space data to the benchmark melter flammability models; Phase II - A nitric–glycolic acid flowsheet melter test (unbubbled and bubbled) to: Define new cold cap reactions and global kinetic parameters in support of the melter flammability model development; Quantify off-gas surging potential of the feed; Characterize off-gas condensate for complete organic and inorganic carbon species. After charging the CEF with cullet from Phase I CEF testing, the melter was slurry-fed with glycolic flowsheet based SB6-Frit 418 melter feed at 36% waste loading and was operated continuously for 25 days. Process data was collected throughout testing and included melter operation parameters and off-gas chemistry. In order to generate off-gas data in support of the flammability model development for the nitric-glycolic flowsheet, vapor space steady state testing in the range of ~300-750°C was conducted under the following conditions, (i) 100% (nominal and excess antifoam levels) and 125% stoichiometry feed and (ii) with and without argon bubbling. Adjustments to feed rate, heater outputs and purge air flow were necessary in order to achieve vapor space temperatures in this range. Surge testing was also completed under nominal conditions for four days with argon bubbling and one day without argon bubbling.« less

Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study.

PubMed

Kolarić, K; Potrebica, V; Vukas, D; Mechl, Z; Sopkova, B

1988-01-01

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.

PubMed

2003-01-01

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.

Beginning Teacher Evaluation Study: Phase II, 1973-74, Final Report: Volume III.2. Reading and Mathematics Observation System: Description and Analysis of Time Expenditures.

ERIC Educational Resources Information Center

Calfee, Robert; Calfee, Kathryn Hoover

The Beginning Teacher Evaluation Study (BTES), Phase II, was a research project on effective teaching behavior--what teachers do that significantly affects what and how pupils learn. The purposes of Phase II were to (1) develop an assessment system for measuring teacher and pupil behaviors and other factors which could influence each of them and…

Model Transformation for a System of Systems Dependability Safety Case

NASA Technical Reports Server (NTRS)

Murphy, Judy; Driskell, Steve

2011-01-01

The presentation reviews the dependability and safety effort of NASA's Independent Verification and Validation Facility. Topics include: safety engineering process, applications to non-space environment, Phase I overview, process creation, sample SRM artifact, Phase I end result, Phase II model transformation, fault management, and applying Phase II to individual projects.

Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PubMed

Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

1993-03-15

To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

Paperless medical records: measuring success.

PubMed

Tobey, Mary Ellen

2004-01-01

North Shore Magnetic Imaging Center (NSMIC) underwent a major transformation of the patient process through an 18-month "Reinvention Project." The project began in October 2002, with an assessment of systems in place. A complete review of each stage of the patient process--scheduling, registration, insurance verification, screening, scanning, transcription, and billing--resulted in the discovery that the paperwork for a single patient examination could go though as many as 20 sets of hands. The project was supported by the formation of an internal team comprised of staff members from all departments (support, patient accounts, and technical), radiologists, and members of the center's senior management team. The team had 2 goals: increase the level of patient care, and create a paperless environment. External teams were formed to address specific areas targeted to support the process. The transformation for all involved--patients, staff, radiologists, and referring physicians--has proved to be very positive. The work, however, was not finished. Upon the project's completion, NSMIC recognized the importance of identifying successes and areas for improvement. These included ongoing reviews of the project's impact on all stakeholders and looking for new technologies and programs to enhance the new systems in place. There are plans for a project "sequel." Strategies are being developed for "Reinvention, Phase II." Elements of these strategies include enhancement of the scheduling programs to create more checks and balances for the staff and investigating an online scheduling option for the center's referring physicians. The purchase and implementation of a voice recognition system--tabled during Phase I--is scheduled for the first quarter of 2005.

The effect of the menstrual cycle on the optic nerve head analysis of migrainous women.

PubMed

Yucel, Iclal; Akar, Munire; Durukan, A; Akar, Yusuf; Taskin, Omur; Dora, Babur; Yilmaz, Nurgul

2005-03-01

To determine the effect of the menstrual cycle on the optic nerve head topographic analysis of normally menstruating migrainous women. Randomly selected one eye of 44 migrainous and 49 healthy control women with regular menstrual cycles were included in the study. All subjects underwent complete ocular examination. Optic nervehead topographic analysis were performed using a confocal scanning laser ophthalmoscope, HRT II (Heidelberg Retinal Tomograph II, software version 1.6;Heidelberg Engineering, Heidelberg, Germany). They were repeated for two times during the menstrual cycle: in follicular phase (7th to 10th day of the cycle) and in the luteal phase (days 3 to 4 before the menstrual bleeding). Serum estradiol, progesterone, and luteinizing hormone measurements were repeated at each menstrual phase. The mean age of migrainous and control subjects were 31.5 + 5.1 years and 33.4 +/- 3.7 years, respectively (P > 0.05). Their mean disc areas were 2.26 +/- 0.46 mm(2) and 1.95 +/- 0.39 mm(2), respectively(P < 0.05). Control subjects did not demonstrate any difference in the disc topography (P > 0.05). The parameter rim volume decreased, while the parameters cup volume and cup shape measure increased significantly in the luteal phase of the migrainous women (all P values <0.05). Mean intraocular pressure of the migrainous women decreased significantly in luteal phase (P < 0.05). Significant differences exist in the optic rim and cup parameters during the menstrual cycle of the migrainous women. Further clinical trials on ocular blood flow changes during the menstrual cycle of the migrainous women may highlight the role of sex steroids in the optic nerve head of the migrainous women.

Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

PubMed

Boonstra, P S; Braun, T M; Taylor, J M G; Kidwell, K M; Bellile, E L; Daignault, S; Zhao, L; Griffith, K A; Lawrence, T S; Kalemkerian, G P; Schipper, M J

2017-07-01

Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Evaluating Adaptation of a Cancer Clinical Trial Decision Aid for Rural Cancer Patients: A Mixed-Methods Approach.

PubMed

Pathak, Swati; George, Nerissa; Monti, Denise; Robinson, Kathy; Politi, Mary C

2018-06-03

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

Effectiveness of safety belt warning and interlock systems

DOT National Transportation Integrated Search

1973-04-01

Rental cars in Fayetteville, N.C., were equipped with four seat belt and warning systems: (Phase I) detachable shoulder and lap belt, no warning system; (Phase II) detachable shoulder and lap belt, warning system (January 1, 1972 standard); (Phase II...

Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

PubMed

Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

2016-01-01

Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible. Deconjugation (mediated by hydrolases) plays an essential role in the conjugation-transport interplay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

PubMed

Fuller, Jill E; Walter, Emmanuel B; Dole, Nancy; O'Hara, Richard; Herring, Amy H; Durkin, Maureen S; Specker, Bonny; Wey, Betty

2017-01-01

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.