5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

5 CFR 308.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Definitions. In this part: Student is an individual who is enrolled not less than half-time in a high school, trade school, technical or vocational institute, junior college, college, university or other accredited... interim between school years if the interim is not more than 5 months and if such individual shows to the...

The cost and impact of the interim federal health program cuts on child refugees in Canada.

PubMed

Evans, Andrea; Caudarella, Alexander; Ratnapalan, Savithiri; Chan, Kevin

2014-01-01

On June 30, 2012, Interim Federal Health Program (IFHP) funding was cut for refugee claimant healthcare. The potential financial and healthcare impacts of these cuts on refugee claimants are unknown. We conducted a one-year retrospective chart review spanning 6 months before and after IFHP funding cuts at The Hospital for Sick Children, a tertiary care children's hospital in Toronto. We analyzed emergency room visits characteristics, admission rates, reasons for admission, and financial records including billing from Medavie Blue Cross. There were 173 refugee children visits to the emergency room in the six months before and 142 visits in the six months after funding cuts. The total amount billed to the IFHP program during the one-year of this study was $131,615. Prior to the IFHP cuts, 46% of the total emergency room bills were paid by IFHP compared to 7% after the cuts (p<0.001). After the cuts to the IFHP, The Hospital for Sick Children was unable to obtain federal health coverage for the vast majority of refugee claimant children registered under the IFHP. This preliminary analysis showed that post-IFHP cuts healthcare costs at the largest tertiary pediatric institution in the country increased.

Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation

PubMed Central

Nakayama, Masaaki; Itami, Noritomo; Suzuki, Hodaka; Hamada, Hiromi; Osaka, Naoyuki; Yamamoto, Ryo; Tsunoda, Kazumasa; Nakano, Hirofumi; Watanabe, Kimio; Zhu, Wan-Jun; Maruyama, Yukio; Terawaki, Hiroyuki; Kabayama, Shigeru; Nakazawa, Ryoichi; Miyazaki, Mariko; Ito, Sadayoshi

2017-01-01

Background and aim It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. Subjects and method 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. Results In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. Conclusion The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment. PMID:28902900

Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease.

PubMed

Galasko, Douglas; Bell, Joanne; Mancuso, Jessica Y; Kupiec, James W; Sabbagh, Marwan N; van Dyck, Christopher; Thomas, Ronald G; Aisen, Paul S

2014-04-29

To examine safety, tolerability, and efficacy of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD). Double-blind, placebo-controlled trial at 40 academic centers (United States). Subjects with AD and Mini-Mental State Examination score 14-26 were randomized to PF-04494700 60 mg/day × 6 days, then 20 mg daily (high dose); 15 mg/day × 6 days, then 5 mg daily (low dose); or placebo, for 18 months. Clinical and laboratory measures were used to evaluate safety and tolerability. The primary efficacy measure was the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog). Secondary measures assessed clinical stage, function, behavior, MRI, and CSF biomarkers. A total of 399 subjects were randomized. In a prespecified interim analysis, when 50% of subjects had completed the 6-month visit, the high dose was associated with confusion, falls, and greater ADAS-cog decline and was discontinued. A second prespecified analysis compared low-dose and placebo groups for futility and safety approximately 12 months after all subjects were randomized. This analysis met criteria for futility, and treatment was discontinued. There were no safety concerns in the low-dose group. Analyses including post-futility data showed decreased decline on the ADAS-cog in the low-dose group at month 18. Other clinical and biomarker measures showed no differences between low-dose treatment and placebo. PF-04494700 at 20 mg/d was associated with increased adverse events and cognitive decline. At 5 mg/d, PF-04494700 had a good safety profile. A potential benefit for this low dose on the ADAS-cog is not conclusive, because of high dropout and discontinuation rates subsequent to the interim analyses. This study provides Class I evidence that in patients with AD high-dose PF-04494700 increased cognitive decline at 6 months and Class IV evidence that low-dose PF-04494700 slowed cognitive decline at 18 months.

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

PubMed Central

2009-01-01

Background Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials. Methods We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination. Results 110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods. Conclusions Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results. PMID:20003383

Contribution of postpolymerization conditioning and storage environments to the mechanical properties of three interim restorative materials.

PubMed

Thompson, Geoffrey A; Luo, Qing

2014-09-01

Because polymer-based interim restorative materials are weak, even well-made restorations sometimes fail before the definitive restoration is ready for insertion. Therefore, knowing which fabrication procedures and service conditions affect mechanical properties is important, particularly over an extended period. The purpose of this study was to evaluate the effect of thermal treatment, surface sealing, thermocycling, storage media, storage temperature, and age on autopolymerizing poly(methylmethacrylate) and bis-acryl interim restorative materials. Outcome measures were flexural strength, Vickers surface microhardness, and impact strength. Flexural strength and microhardness of poly(methylmethacrylate) (Jet Acrylic) and 2 bis-acryl-composite resin (Protemp 3 Garant and Integrity) interim restorative materials were evaluated as affected by storage media, storage temperature, storage time, thermocycling, postpolymerization thermal treatment, or application of a surface sealer. In total, 2880 beam specimens (25×2×2 mm) were fabricated. Mechanical property analyses were made at 10 days, 30 days, 6 months, and 1 year after specimen preparation. Flexural strength was determined by using a 3-point bending test in a universal testing machine with a 1 kN load cell at a crosshead speed of 5.0 mm min(-1). Fracture specimens were recovered and used for determining Vickers microhardness. Measurements were made with a 0.1 N load and 15 second dwell time. Three microhardness measurements were made for each specimen, and the mean was used for reporting Vickers microhardness. Notched impact specimens (64×12.7×6.35 mm) were fabricated from Jet, Protemp 3 Garant, and Integrity interim restorative materials, yielding 288 impact specimens. Impact strengths were assessed at 10 days, 30 days, 6 months, and 1 year with a 2 J pendulum. The effects of the various experimental treatments were determined and rank ordered with analysis of variance, F ratios, and least square means differences Student t tests (α=.05). All experimental treatments investigated had significant effects on flexural strength, with material (P<.001) and thermocycling (P<.001) being dominant. Moreover, all experimental treatments investigated had a significant overall impact on Vickers microhardness with material (P<.001) and Palaseal glaze (P<.001) showing large effects. Material (P<.001) and age (P=.010) had a significant effect on impact strength. Mechanical properties of some interim polymeric materials can be improved by postpolymerization heat treatments or surface glazing. This procedure may extend the useful lifetime of some bis-acryl interim restorations. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Immediate provisionalization in the esthetic zone: 1-year interim results from a prospective single-cohort multicenter study evaluating 3.0-mm-diameter tapered implants.

PubMed

Kolinski, Martin; Hess, Pablo; Leziy, Sonia; Friberg, Bertil; Bellucci, Gionata; Trisciuoglio, Davide; Wagner, Wilfried; Moergel, Maximilian; Pozzi, Alessandro; Wiltfang, Jörg; Behrens, Eleonore; Zechner, Werner; Vasak, Christoph; Weigl, Paul

2018-07-01

The aim of this interim analysis of a 5-year prospective multicenter study is to evaluate clinical and radiological performance of immediately provisionalized 3.0-mm-diameter tapered implants. Patients needing implant rehabilitation of maxillary lateral incisors or mandibular lateral and central incisors were treated with 3.0-mm-diameter implants placed in extraction or healed sites and immediately provisionalized. Clinical and radiographic examinations were performed at implant insertion, 6 months thereafter, and are ongoing. Marginal bone levels and changes, complications, the papilla, plaque, and bleeding indices, and the pink esthetic score (PES) were evaluated at each follow-up visit. Of 112 enrolled patients, 77 patients (91 implants) met the inclusion criteria. Seventy-one patients with 82 implants completed the 1-year follow-up. Three implants failed yielding a CSR of 96.7%. All failures occurred within the first 3 months after implant insertion. Marginal bone level changes from insertion to 6 months was - 0.57 ± 1.30 mm (n = 75) and from insertion to 12 months - 0.25 ± 1.38 mm (n = 72). Fifteen non-serious complications were recorded. Papilla index score and PES improved at the 1-year follow-up. Plaque formation and bleeding-on-probing showed no statistically significant differences between the 6-month and the 1-year visit. This 1-year analysis demonstrated high survival, stable bone levels, and healthy soft tissue with 3.0-mm-diameter implants. Narrow diameter implants are a safe and predictable treatment option in patients with limited bone volume and/or limited interdental space and eligible for immediate loading protocols.

Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149

PubMed Central

Li, Ling; Li, Xin; Wang, Xinhua; Fu, Xiaorui; Ma, Wang; Qin, Yanru; Li, Wencai; Wu, Jingjing; Sun, Zhenchang; Zhang, Xudong; Nan, Feifei; Chang, Yu; Li, Zhaoming; Zhang, Dandan; Wang, Guannan; Yan, Jiaqin; Su, Liping; Wang, Jinghua; Xue, Hongwei; Young, Ken H.; Zhang, Mingzhi

2016-01-01

To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149. PMID:27384676

Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of Safety in 403 Patients

PubMed Central

Sojitra, Nilesh; Glumicic, Sinisa; Vlok, Jacobus A.; O’Toole, Greg; Hannan, S. Alam; Sabbagh, Walid

2018-01-01

Background: The Earfold system, a new treatment for the correction of prominent ears, consists of 3 components: the Earfold implant, the Earfold introducer, and the Prefold positioner. Methods: This is an interim report based on an ongoing analysis of safety in a series of patients treated for prominent ears with the Earfold implant between February 2013 and September 2014. Safety was assessed based on adverse event reports and the need for implant revision; follow-up is ongoing. Results: Seven surgeons used 1,200 Earfold implants to treat 403 patients (ages, 7–70 years; 63% male); the time since the initial implant procedure now ranges from 30 to 48 months. To date, 145 patients (36%) have returned for a follow-up visit (mean, 7.7 months [range, 1–34 months]). Adverse events requiring intervention have affected 39 of 403 (9.7%) patients; these include implant revisions (n = 17 [4.2%], most often due to implant visibility), skin erosion over the implant (n = 15 [3.7%]), and infection (n = 7 [1.7%]). Bleeding, recurrence of prominence, hematoma, deformity, or adverse scarring did not occur. Conclusions: This interim analysis has shown that Earfold prominent ear correction system is associated with relatively few adverse events that require intervention; a small number of patients experienced infection, implant extrusion, or implant visibility that required revision. Most adverse events were related to either patient selection or technical errors at implantation. It is expected that with continued use of Earfold by surgeons experienced in otoplasty, the adverse event incidence will decrease. PMID:29464160

A Systems Analysis of the Library and Information Science Statistical Data System: The Preliminary Study. Interim Report.

ERIC Educational Resources Information Center

Hamburg, Morris; And Others

The long-term goal of this investigation is to design and establish a national model for a system of library statistical data. This is a report on The Preliminary Study which was carried out over an 11-month period ending May, 1969. The objective of The Preliminary Study was to design and delimit The Research Investigation in the most efficient…

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

PubMed

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.

PubMed

Swain, Sandra M; Baselga, José; Kim, Sung-Bae; Ro, Jungsil; Semiglazov, Vladimir; Campone, Mario; Ciruelos, Eva; Ferrero, Jean-Marc; Schneeweiss, Andreas; Heeson, Sarah; Clark, Emma; Ross, Graham; Benyunes, Mark C; Cortés, Javier

2015-02-19

In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months. We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis. The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained. In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).

A randomized, controlled trial of oral propranolol in infantile hemangioma.

PubMed

Léauté-Labrèze, Christine; Hoeger, Peter; Mazereeuw-Hautier, Juliette; Guibaud, Laurent; Baselga, Eulalia; Posiunas, Gintas; Phillips, Roderic J; Caceres, Hector; Lopez Gutierrez, Juan Carlos; Ballona, Rosalia; Friedlander, Sheila Fallon; Powell, Julie; Perek, Danuta; Metz, Brandie; Barbarot, Sebastien; Maruani, Annabel; Szalai, Zsuzsanna Zsofia; Krol, Alfons; Boccara, Olivia; Foelster-Holst, Regina; Febrer Bosch, Maria Isabel; Su, John; Buckova, Hana; Torrelo, Antonio; Cambazard, Frederic; Grantzow, Rainer; Wargon, Orli; Wyrzykowski, Dariusz; Roessler, Jochen; Bernabeu-Wittel, Jose; Valencia, Adriana M; Przewratil, Przemyslaw; Glick, Sharon; Pope, Elena; Birchall, Nicholas; Benjamin, Latanya; Mancini, Anthony J; Vabres, Pierre; Souteyrand, Pierre; Frieden, Ilona J; Berul, Charles I; Mehta, Cyrus R; Prey, Sorilla; Boralevi, Franck; Morgan, Caroline C; Heritier, Stephane; Delarue, Alain; Voisard, Jean-Jacques

2015-02-19

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

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

Bush, David A., E-mail: dbush@llu.edu; Smith, Jason C.; Slater, Jerry D.

2016-05-01

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractionsmore » over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.« less

Retention of long-term interim restorations with sodium fluoride enriched interim cement

NASA Astrophysics Data System (ADS)

Strash, Carolyn

Purpose: Interim fixed dental prostheses, or "provisional restorations", are fabricated to restore teeth when definitive prostheses are made indirectly. Patients undergoing extensive prosthodontic treatment frequently require provisionalization for several months or years. The ideal interim cement would retain the restoration for as long as needed and still allow for ease of removal. It would also avoid recurrent caries by preventing demineralization of tooth structure. This study aims to determine if adding sodium fluoride varnish to interim cement may assist in the retention of interim restorations. Materials and methods: stainless steel dies representing a crown preparation were fabricated. Provisional crowns were milled for the dies using CAD/CAM technology. Crowns were provisionally cemented onto the dies using TempBond NE and NexTemp provisional cements as well as a mixture of TempBond NE and Duraphat fluoride varnish. Samples were stored for 24h then tested or thermocycled for 2500 or 5000 cycles before being tested. Retentive strength of each cement was recorded using a universal testing machine. Results: TempBond NE and NexTemp cements performed similarly when tested after 24h. The addition of Duraphat significantly decreased the retention when added to TempBond NE. NexTemp cement had high variability in retention over all tested time periods. Thermocycling for 2500 and 5000 cycles significantly decreased the retention of all cements. Conclusions: The addition of Duraphat fluoride varnish significantly decreased the retention of TempBond NE and is therefore not recommended for clinical use. Thermocycling significantly reduced the retention of TempBond NE and NexTemp. This may suggest that use of these cements for three months, as simulated in this study, is not recommended.

A randomized controlled trial of interim methadone maintenance.

PubMed

Schwartz, Robert P; Highfield, David A; Jaffe, Jerome H; Brady, Joseph V; Butler, Carol B; Rouse, Charles O; Callaman, Jason M; O'Grady, Kevin E; Battjes, Robert J

2006-01-01

Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. A methadone treatment program in Baltimore. A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

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

Laack, Nadia N.; Ballman, Karla V.; Mayo Clinic Cancer Center, Rochester, MN

Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan,more » adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.« less

Annotating MYC Status in Treatment-Resistant Metastatic Castration-Resistant Prostate Cancer With Gallium-68 Citrate PET

DTIC Science & Technology

2017-09-01

ongoing and interim analysis is planned within the next 6 months. Planned analyses include: 1) correlation of gallium citrate uptake on PET with MYC...utility of Gallium citrate PET as a pharmacodynamic and predictive biomarker of MYC pathway inhibition in mCRPC. Correlative pre- and post-treatment...completed Milestone Achieved: Last patient completes study follow up scan 36 Not yet completed Assess correlation between SUVmax on gallium

76 FR 38552 - Amendments to Regulations Regarding Major Life-Changing Events Affecting Income-Related Monthly...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... to Regulations Regarding Major Life-Changing Events Affecting Income-Related Monthly Adjustment.... SUMMARY: This final rule adopts, without change, the interim final rule with request for comments we... consider major life-changing events for the Medicare Part B income- related monthly adjustment amount...

The role of the Data and Safety Monitoring Board in a clinical trial: The CRISIS Study

PubMed Central

Holubkov, Richard; Casper, T. Charles; Dean, J. Michael; Anand, K. J. S.; Zimmerman, Jerry; Meert, Kathleen L.; Newth, Christopher J. L.; Berger, John; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

2012-01-01

Objective Randomized clinical trials are commonly overseen by a data and safety monitoring board (DSMB) comprised of experts in medicine, ethics, and biostatistics. DSMB responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. DSMB decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate DSMB oversight into the design, monitoring, and reporting of randomized trials. Design Case study, narrative review. Methods The DSMB’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. Findings The NIH-appointed CRISIS DSMB was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested DSMB interim review before opening CRISIS to children below one year of age. The first interim analysis found higher 28-day mortality in one treatment arm. The DSMB maintained trial closure to younger children, and requested a second interim data review six months later. At this second meeting, mortality was no longer of concern, while a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the DSMB elected to examine conditional power, and unmask treatment arm identities. Upon finding somewhat greater efficacy in the placebo arm, the DSMB recommended stopping CRISIS due to futility. Conclusions The design and operating procedures of a multicenter randomized trial must consider a pivotal DSMB role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The DSMB must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups. PMID:23392377

Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study.

PubMed

Arzimanoglou, Alexis; Ferreira, Jose A; Satlin, Andrew; Mendes, Shannon; Williams, Betsy; Critchley, David; Schuck, Edgar; Hussein, Ziad; Kumar, Dinesh; Dhadda, Shobha; Bibbiani, Francesco

2016-05-01

A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects ≥ 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs. Interim safety results showed that treatment-emergent adverse events (TEAEs) were similar between the rufinamide (22 [88.0%]) and any-other-AED group (9 [81.8%]), with most events considered mild or moderate. A population PK analysis was conducted including plasma rufinamide concentrations from Study 303 and two other study populations of LGS subjects ≥ 4 years. The rufinamide PK profile was dose independent. The apparent clearance (CL/F) estimated from the PK model was 2.19 L/h; it was found to increase significantly as a function of body weight. Coadministration of valproic acid significantly decreased rufinamide CL/F. CL/F was not significantly affected by other concomitant AEDs, age, gender, race, hepatic function, or renal function. No adjustments to body weight-based rufinamide dosing in subjects ≥ 1 to < 4 years are necessary. Rufinamide was safe and well tolerated in these pediatric subjects. Results from the interim analysis demonstrate that rufinamide's safety and PK profile is comparable in subjects ≥ 1 to < 4 and ≥ 4 years with LGS. Study 303 (clinicaltrials.gov: NCT01405053). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improving the Quality of Radiographs in Neonatal Intensive Care Unit Utilizing Educational Interventions.

PubMed

Gupta, Ashish O; Rorke, Jeanne; Abubakar, Kabir

2015-08-01

We aimed to develop an educational tool to improve the radiograph quality, sustain this improvement overtime, and reduce the number of repeat radiographs. A three phase quality control study was conducted at a tertiary care NICU. A retrospective data collection (phase1) revealed suboptimal radiograph quality and led to an educational intervention and development of X-ray preparation checklist (primary intervention), followed by a prospective data collection for 4 months (phase 2). At the end of phase 2, interim analysis revealed a gradual decline in radiograph quality, which prompted a more comprehensive educational session with constructive feedback to the NICU staff (secondary intervention), followed by another data collection for 6 months (phase 3). There was a significant improvement in the quality of radiographs obtained after primary educational intervention (phase 2) compared with phase 1 (p < 0.001). During interim analysis after phase 2, radiograph quality declined but still remained significantly better than phase 1. Secondary intervention resulted in significant improvement in radiograph quality to > 95% in all domains of image quality. No radiographs were repeated in phase 3, compared with 5.8% (16/277) in phase 1. A structured, collaborated educational intervention successfully improves the radiograph quality and decreases the need for repeat radiographs and radiation exposure in the neonates. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study.

PubMed

van der Heijde, Désirée; Tanaka, Yoshiya; Fleischmann, Roy; Keystone, Edward; Kremer, Joel; Zerbini, Cristiano; Cardiel, Mario H; Cohen, Stanley; Nash, Peter; Song, Yeong-Wook; Tegzová, Dana; Wyman, Bradley T; Gruben, David; Benda, Birgitta; Wallenstein, Gene; Krishnaswami, Sriram; Zwillich, Samuel H; Bradley, John D; Connell, Carol A

2013-03-01

The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported. In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure. At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were -0.40 (significance not declared due to step-down procedure) and -0.54 (P < 0.0001), respectively, versus -0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies. Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX. Copyright © 2013 by the American College of Rheumatology.

Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma.

PubMed

Atkins, Michael; Coutinho, Anna D; Nunna, Sasikiran; Gupte-Singh, Komal; Eaddy, Michael

2018-02-01

The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010-September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to -10.2%). The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but should be combined with clinical judgement.

Immunotherapy for recurrent malignant glioma: an interim report on survival.

PubMed

Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

1990-12-01

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Texturing of concrete pavements : interim report No. 3.

DOT National Transportation Integrated Search

1977-08-01

The scope of this report is to describe the results obtained at the end of thirty-six months for the third twelve-month period of this field research project. It includes the construction of test sections and the evaluation period after the project w...

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.

PubMed

Mercuri, Eugenio; Darras, Basil T; Chiriboga, Claudia A; Day, John W; Campbell, Craig; Connolly, Anne M; Iannaccone, Susan T; Kirschner, Janbernd; Kuntz, Nancy L; Saito, Kayoko; Shieh, Perry B; Tulinius, Már; Mazzone, Elena S; Montes, Jacqueline; Bishop, Kathie M; Yang, Qingqing; Foster, Richard; Gheuens, Sarah; Bennett, C Frank; Farwell, Wildon; Schneider, Eugene; De Vivo, Darryl C; Finkel, Richard S

2018-02-15

Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537 .).

Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro

2016-10-01

To evaluate the efficacy and safety of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes. We conducted interim analyses at 3 months of a 3-year prospective study of patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015, and whose data were locked by 16 January 2016. Changes in glycemic control, blood pressure, and laboratory variables from baseline, and incidence of adverse drug reactions (ADRs). Of 11,412 patients initially registered, efficacy and safety data were available for 3481 (30.5%) and 4360 (38.2%) patients, respectively. Hemoglobin A1c and fasting plasma glucose decreased by 0.67% and 28.8 mg/dL, respectively, at 3 months/last assessment (both P < .001) from baseline (8.00% and 166.4 mg/dL, respectively). Blood pressure and lipid levels also improved significantly. There were 258 ADRs in 194 patients. The ADRs included 'renal and urinary disorders' (system organ class) in 110 patients (2.5%). These 3-month interim results indicate that ipragliflozin improved glycemic control, lipids, and blood pressure with low rates of ADRs in Japanese patients with type 2 diabetes in real-world clinical practice. The results were consistent with those of placebo-controlled, randomized clinical trials. Clinicaltrials.gov identifier: NCT02479399.

Mental health pharmacists as interim prescribers

PubMed Central

2017-01-01

Introduction: Turnover leading to fluctuations in prescriber availability presents many challenges, most notably in access to and continuity of care. In 2015, the Veterans Affairs Eastern Colorado Healthcare System (VA ECHCS) experienced a period of significant mental health prescriber turnover leading to patient utilization of psychiatric emergency services (PES) for nonemergent medication management. The resulting increase in volume placed excessive stress on PES prescribers. Mental health pharmacists have opportunities to provide interim medication management while patients are between prescribers. Methods: This study was a retrospective, cohort study of patients unassigned to an outpatient mental health prescriber due to prescriber turnover, receiving care at VA ECHCS between October 1, 2015, and February 28, 2016. The primary outcome was the number of pharmacist interventions performed. Secondary outcomes characterize the interventions performed and describe the change in the mean monthly volume of patients presenting to PES. Results: In this veteran population, 152 interventions were performed in 81 unique patients. The most common intervention was prescription renewals (80%). Interventions most commonly involved antidepressants (28%), antipsychotics (10%), and mood stabilizers (10%). Before initiation of the clinic, Denver VA PES experienced a mean of 300 monthly visits. After clinic implementation, PES visits decreased significantly to a mean of 237 visits per month (P = .041). Discussion: The pharmacist interim prescriber clinic was associated with a significant decrease in mean number of patients seen per month in PES. The success of the clinic also contributed to interest by the mental health service to expand clinical pharmacy services.

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility.

PubMed

Walter, S D; Han, H; Briel, M; Guyatt, G H

2017-04-30

In this paper, we consider the potential bias in the estimated treatment effect obtained from clinical trials, the protocols of which include the possibility of interim analyses and an early termination of the study for reasons of futility. In particular, by considering the conditional power at an interim analysis, we derive analytic expressions for various parameters of interest: (i) the underestimation or overestimation of the treatment effect in studies that stop for futility; (ii) the impact of the interim analyses on the estimation of treatment effect in studies that are completed, i.e. that do not stop for futility; (iii) the overall estimation bias in the estimated treatment effect in a single study with such a stopping rule; and (iv) the probability of stopping at an interim analysis. We evaluate these general expressions numerically for typical trial scenarios. Results show that the parameters of interest depend on a number of factors, including the true underlying treatment effect, the difference that the trial is designed to detect, the study power, the number of planned interim analyses and what assumption is made about future data to be observed after an interim analysis. Because the probability of stopping early is small for many practical situations, the overall bias is often small, but a more serious issue is the potential for substantial underestimation of the treatment effect in studies that actually stop for futility. We also consider these ideas using data from an illustrative trial that did stop for futility at an interim analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.

PubMed

Jones, Jeffrey A; Mato, Anthony R; Wierda, William G; Davids, Matthew S; Choi, Michael; Cheson, Bruce D; Furman, Richard R; Lamanna, Nicole; Barr, Paul M; Zhou, Lang; Chyla, Brenda; Salem, Ahmed Hamed; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Coutre, Steven; Woyach, Jennifer; Byrd, John C

2018-01-01

Therapy targeting Bruton's tyrosine kinase (BTK) with ibrutinib has transformed the treatment of chronic lymphocytic leukaemia. However, patients who are refractory to or relapse after ibrutinib therapy have poor outcomes. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 active in previously treated patients with relapsed or refractory chronic lymphocytic leukaemia. In this study, we assessed the activity and safety of venetoclax in patients with chronic lymphocytic leukaemia who are refractory to or relapse during or after ibrutinib therapy. In this interim analysis of a multicentre, open-label, non-randomised, phase 2 trial, we enrolled patients aged 18 years or older with a documented diagnosis of chronic lymphocytic leukaemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern Cooperative Oncology Group performance score of 2 or lower. All patients had relapsed or refractory disease after previous treatment with a BCR signalling pathway inhibitor. All patients were screened for Richter's transformation and cases confirmed by biopsy were excluded. Eligible patients received oral venetoclax, starting at 20 mg per day with stepwise dose ramp-up over 5 weeks to 400 mg per day. Patients with rapidly progressing disease received an accelerated dosing schedule (to 400 mg per day by week 3). The primary endpoint was overall response, defined as the proportion of patients with an overall response per investigator's assessment according to IWCLL criteria. All patients who received at least one dose of venetoclax were included in the activity and safety analyses. This study is ongoing; data for this interim analysis were collected per regulatory agencies' request as of June 30, 2017. This trial is registered with ClinicalTrials.gov, number NCT02141282. Between September, 2014, and November, 2016, 127 previously treated patients with relapsed or refractory chronic lymphocytic leukaemia were enrolled from 15 sites across the USA. 91 patients had received ibrutinib as the last BCR inhibitor therapy before enrolment, 43 of whom were enrolled in the main cohort and 48 in the expansion cohort recruited later after a protocol amendment. At the time of analysis, the median follow-up was 14 months (IQR 8-18) for all 91 patients, 19 months (9-27) for the main cohort, and 12 months (8-15) for the expansion cohort. 59 (65%, 95% CI 53-74) of 91 patients had an overall response, including 30 (70%, 54-83) of 43 patients in the main cohort and 29 (60%, 43-72) of 48 patients in the expansion cohort. The most common treatment-emergent grade 3 or 4 adverse events were neutropenia (46 [51%] of 91 patients), thrombocytopenia (26 [29%]), anaemia (26 [29%]), decreased white blood cell count (17 [19%]), and decreased lymphocyte count (14 [15%]). 17 (19%) of 91 patients died, including seven because of disease progression. No treatment-related deaths occurred. The results of this interim analysis show that venetoclax has durable clinical activity and favourable tolerability in patients with relapsed or refractory chronic lymphocytic leukaemia whose disease progressed during or after discontinutation of ibrutinib therapy. The durability of response to venetoclax will be assessed in the final analysis in 2019. AbbVie, Genentech. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-term functional outcomes of patients with very mild stroke: does a NIHSS score of 0 mean no disability? An interim analysis of the KOSCO study.

PubMed

Chang, Won Hyuk; Sohn, Min Kyun; Lee, Jongmin; Kim, Deog Young; Lee, Sam-Gyu; Shin, Yong-Il; Oh, Gyung-Jae; Lee, Yang-Soo; Joo, Min Cheol; Han, Eun Young; Kim, Min Su; Jang, Shin Yi; Kim, Jeong Hyun; Kim, Yun-Hee

2017-05-01

To explore the long-term functional outcomes of stroke patients with very mild severity at 6 months after stroke. This study presents the interim results of the Korean Stroke Cohort for Functioning and Rehabilitation. On day 7, stroke evaluation was performed using the functional assessment battery including the National Institute of Health Stroke Scale (NIHSS). At 6 months after stroke, functional outcomes using the face-to-face functional assessment battery including Functional Independence Measure (FIM) were analyzed in the patients who had a score of 0 on the NIHSS at 7 days after stroke onset. In the very mild stroke group, 455 patients were followed up at 6 months. Out of these patients, 11.0% had impairments in cognitive function, 14.1% had motor impairment, and 2.1% had impairments in their mobility measured by the functional assessment battery. At 6 months after onset, 3.3% of stroke survivors without recurrence showed dependency according to the FIM. Many acute stroke patients with mild stroke severity as assessed by the NIHSS had impairments in various functional domains, and could have been easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy might be better identified by the functional assessment battery. Implications for rehabilitation Many acute stroke patients with mild stroke severity assessed by NIHSS could be easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy should be evaluated using a functional assessment battery rather than the NIHSS.

The DENALI Trial: an interim analysis of a prospective, multicenter study of the Denali retrievable inferior vena cava filter.

PubMed

Stavropoulos, S William; Sing, Ronald F; Elmasri, Fakhir; Silver, Mitchell J; Powell, Alex; Lynch, Frank C; Aal, Ahmed Kamel Abdel; Lansky, Alexandra J; Settlage, Richard A; Muhs, Bart E

2014-10-01

To assess safety and effectiveness of a nitinol retrievable inferior vena cava (IVC) filter in patients who require caval interruption to protect against pulmonary embolism (PE). Two hundred patients with temporary indications for an IVC filter were enrolled in this prospective, multicenter clinical study. Patients undergoing filter implantation were to be followed for 2 years or for 30 days after filter retrieval. At the time of the present interim report, all 200 patients had been enrolled in the study, and 160 had undergone a retrieval attempt or been followed to 6 months with their filter in place. Primary study endpoints included technical and clinical success of filter placement and retrieval. Patients were also evaluated for recurrent PE, new or worsening deep vein thrombosis, and filter migration, fracture, penetration, and tilt. Clinical success of placement was achieved in 94.5% of patients (172 of 182), with a one-sided lower limit of the 95% confidence interval of 90.1%. Technical success rate of filter placement was 99.5%. Technical success rate of retrieval was 97.3%; 108 filters were retrieved in 111 attempts. In two cases, the filter apex could not be engaged with a snare, and one device was engaged but could not be removed. Filter retrievals occurred at a mean indwell time of 165 days (range, 5-632 d). There were no instances of filter fracture, migration, or tilt greater than 15° at the time of retrieval or 6-month follow-up. In this interim report, the nitinol retrievable IVC filter provided protection against pulmonary embolism, and the device could be retrieved with a low rate of complications. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

PubMed

Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

2015-01-08

Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

STARPAHC Interim Evaluation Report, May 1975 - April 1976

NASA Technical Reports Server (NTRS)

1976-01-01

The primary goals of the STARPAHC Program are to provide data for developing health care for future manned spacecraft, and to establish the feasibility of the STARPAHC concept for improving the delivery of health care to remote areas on earth. Accordingly, the hardware and medical evaluations initiated during the first 6 months of system operation were continued and expanded during the second 6-month period. The evaluations are based on what has proven to be a relatively stabilized 6-month period wherein system failures which occurred during the initial shakedown period in the first 6 months have been minimized. Early trends and performance data reported in the first semi-annual report were reexamined to either verify, modify or change earlier conclusions. The highlights are given of the total year of operation with emphasis on comparisons between the first and second semi-annual reporting period. In addition, an early analysis of costs is summarized.

78 FR 20503 - Energy Conservation Program: Availability of the Interim Technical Support Document for High...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... Conservation Program: Availability of the Interim Technical Support Document for High-Intensity Discharge Lamps... high-intensity discharge (HID) lamps energy conservation standards in the Federal Register. This... interim analysis for high- intensity discharge lamps energy conservation standards. The notice provided...

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

40 CFR 265.304 - Monitoring and inspection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for two consecutive months, the amount of liquids in the sumps must be recorded at least quarterly. If... sump until the liquid level again stays below the pump operating level for two consecutive months. (c... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

40 CFR 265.304 - Monitoring and inspection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for two consecutive months, the amount of liquids in the sumps must be recorded at least quarterly. If... sump until the liquid level again stays below the pump operating level for two consecutive months. (c... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

40 CFR 265.304 - Monitoring and inspection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for two consecutive months, the amount of liquids in the sumps must be recorded at least quarterly. If... sump until the liquid level again stays below the pump operating level for two consecutive months. (c... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

40 CFR 265.304 - Monitoring and inspection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for two consecutive months, the amount of liquids in the sumps must be recorded at least quarterly. If... sump until the liquid level again stays below the pump operating level for two consecutive months. (c... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

40 CFR 265.304 - Monitoring and inspection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... for two consecutive months, the amount of liquids in the sumps must be recorded at least quarterly. If... sump until the liquid level again stays below the pump operating level for two consecutive months. (c... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

Interim results of two-year toxicological studies in rats of vinylidene chloride incorporated in the drinking water or administered by repeated inhalation

PubMed Central

Rampy, L. W.; Quast, J. F.; Humiston, C. G.; Balmer, M. F.; Schwetz, B. A.

1977-01-01

Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean ± S.D. concentrations of 0, 68 ± 13, 106 ± 22, and 220 ± 35 ppm which produced mean ± S.D. dosage levels of 0, 5.9 ± 0.6, 10.0 ± 1.2, and 19.3 ± 2.7 mg/kg for male rats and 0, 7.5 ± 0.4, 12.6 ± 1.1, and 25.6 ± 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls. PMID:612457

The role of the Data and Safety Monitoring Board in a clinical trial: the CRISIS study.

PubMed

Holubkov, Richard; Casper, T Charles; Dean, J Michael; Anand, K J S; Zimmerman, Jerry; Meert, Kathleen L; Newth, Christopher J L; Berger, John; Harrison, Rick; Willson, Douglas F; Nicholson, Carol

2013-05-01

Randomized clinical trials are commonly overseen by a Data and Safety Monitoring Board comprised of experts in medicine, ethics, and biostatistics. Data and Safety Monitoring Board responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. Data and Safety Monitoring Board decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate Data and Safety Monitoring Board oversight into the design, monitoring, and reporting of randomized trials. Case study, narrative review. The Data and Safety Monitoring Board's role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. The National Institutes of Health-appointed CRISIS Data and Safety Monitoring Board was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested Data and Safety Monitoring Board interim review before opening CRISIS to children below 1 yr of age. The first interim analysis found higher 28-day mortality in one treatment arm. The Data and Safety Monitoring Board maintained trial closure to younger children and requested a second interim data review 6 months later. At this second meeting, mortality was no longer of concern, whereas a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the Data and Safety Monitoring Board elected to examine conditional power and unmask treatment arm identities. On finding somewhat greater efficacy in the placebo arm, the Data and Safety Monitoring Board recommended stopping CRISIS due to futility. The design and operating procedures of a multicenter randomized trial must consider a pivotal Data and Safety Monitoring Board role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The Data and Safety Monitoring Board must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups.

Short-term results of a prospective randomized evaluator blinded multicenter study comparing TVT and TVT-Secur.

PubMed

Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Etén-Bergqvist, Christina; Persson, Jan

2011-07-01

The aim of this prospective randomized multicenter study was to compare TVT (tension-free vaginal tape) with TVT-Secur in terms of efficacy and safety. We set out to enrol 280 stress incontinent women with a half time interim analysis of short-term cure and a continuous registration of adverse events. Of 133 randomized women, 126 were operated and 123 (TVT n = 62, TVT-Secur n = 61) available for 2 months follow-up. No significant differences were found between groups regarding demographics or grade of incontinence. At 2 months follow-up, subjective cure rate following TVT-Secur was significantly lower than for TVT (72% and 92%, respectively, p = 0.01). Three major complications occurred in the TVT-Secur group: tape erosion into the urethra, a tape inadvertently placed inside the bladder, and an immediate postoperative bleeding from the corona mortis. No major complications occurred in the TVT group. No significant differences were found between groups regarding perioperative bleeding, hospital stay, urge symptoms, or postoperative urinary tract infections. Median time for surgery was 13 and 22 min for TVT-Secur and TVT, respectively (p < 0.0001). In a prospective randomized controlled study, the TVT-Secur procedure had a significantly lower subjective cure rate than the retropubic TVT procedure. Due to this, in addition to three serious complications in the TVT-Secur group, we decided to stop further enrolment after the interim analysis. We discourage from further use of the TVT-Secur.

Evaluation and analysis of Seasat-A scanning multichannel Microwave Radiometer (SMMR) Antenna Pattern Correction (APC) algorithm

NASA Technical Reports Server (NTRS)

Kitzis, J. L.; Kitzis, S. N.

1979-01-01

The brightness temperature data produced by the SMMR final Antenna Pattern Correction (APC) algorithm is discussed. The algorithm consisted of: (1) a direct comparison of the outputs of the final and interim APC algorithms; and (2) an analysis of a possible relationship between observed cross track gradients in the interim brightness temperatures and the asymmetry in the antenna temperature data. Results indicate a bias between the brightness temperature produced by the final and interim APC algorithm.

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

PubMed

Chapman, Paul B; Hauschild, Axel; Robert, Caroline; Haanen, John B; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O'Day, Steven J; Sosman, Jeffrey A; Kirkwood, John M; Eggermont, Alexander M M; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J; Flaherty, Keith T; McArthur, Grant A

2011-06-30

Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

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

Balkwill, D.L.; Reeves, R.H.

The present document is an interim technical report in which we describe the research which has been completed during the seven-month period since the start of the grant. Progress is summarized in two main areas. The first is microbiological characterization of subsurface materials from the Hanford reservation and the Idaho National Engineering Laboratory, and the second is phylogenetic characterization of these microorganisms. The major tools used for phylogenetic characterization are RFLP analysis of PCR derived material and 16S rRNA sequencing. A description of manuscripts ready for publication is also provided. 4 refs. (MHB)

Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.

PubMed

Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan; Sengeløv, Lisa; Saad, Fred; Houede, Nadine; Ostler, Peter; Stenzl, Arnulf; Daugaard, Gedske; Jones, Robert; Laestadius, Fredrik; Ullèn, Anders; Bahl, Amit; Castellano, Daniel; Gschwend, Juergen; Maurina, Tristan; Chow Maneval, Edna; Wang, Shaw-Ling; Lechuga, Maria Jose; Paolini, Jolanda; Chen, Isan

2014-01-10

We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer.

PubMed

Soria, Jean-Charles; Ohe, Yuichiro; Vansteenkiste, Johan; Reungwetwattana, Thanyanan; Chewaskulyong, Busyamas; Lee, Ki Hyeong; Dechaphunkul, Arunee; Imamura, Fumio; Nogami, Naoyuki; Kurata, Takayasu; Okamoto, Isamu; Zhou, Caicun; Cho, Byoung Chul; Cheng, Ying; Cho, Eun Kyung; Voon, Pei Jye; Planchard, David; Su, Wu-Chou; Gray, Jhanelle E; Lee, Siow-Ming; Hodge, Rachel; Marotti, Marcelo; Rukazenkov, Yuri; Ramalingam, Suresh S

2018-01-11

Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

Relationship between brain volumetric changes and interim drinking at six months in alcohol-dependent patients.

PubMed

Segobin, Shailendra H; Chételat, Gaël; Le Berre, Anne-Pascale; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène; Pitel, Anne-Lise

2014-03-01

Chronic alcohol consumption results in brain damage potentially reversible with abstinence. It is however difficult to gauge the degree of recovery of brain tissues with abstinence since changes are subtle and a significant portion of patients relapse. State-of-the-art morphometric methods are increasingly used in neuroimaging studies to detect subtle brain changes at a voxel level. Our aim was to use the most refined morphometric methods to observe in alcohol dependence the relationship between volumetric changes and interim drinking over a 6-month follow-up. Overall, 19 patients with alcohol dependence received volumetric T1-weighted magnetic resonance imaging (MRI) after detoxification. A 6-month follow-up study was then conducted, during which 11 of them received a second MRI scan. First, correlations were conducted between gray matter (GM) and white matter (WM) volumes of patients at alcohol treatment entry and the amount of alcohol consumed between treatment entry and follow-up. Second, longitudinal analyses were performed from pairs of MRI scans using tensor-based morphometry in the 11 patients, and correlations were computed between the resultant Jacobian maps of GM and WM and interim drinking. Our preliminary results showed that, among others, alcoholics with smaller thalamus at alcohol treatment entry tended to resume with heavy alcohol consumption (p < 0.005 uncorrected [unc.]). Our longitudinal study revealed an overall inverse relationship between recovery of brain structures like the cerebellum, striatum, and cingulate gyrus, and the amount of alcohol consumed over the 6-month follow-up (p < 0.005 unc.). The recovery could be observed not only with strict abstinence but also in cases of moderate resumption of alcohol consumption, when there had been no drastic relapse into alcohol dependence. Those preliminary findings indicate that the volume of the thalamus at treatment entry may have an influence on subsequent interim drinking. There is recovery of certain brain regions even when patients resume with moderate, but not drastic, alcohol consumption. Copyright © 2014 by the Research Society on Alcoholism.

75 FR 12217 - Notice of Availability for Comments Regarding the Planned Environmental Assessment Interim Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... public comments for a planned Environmental Assessment. The Corps is directed to conduct a study of.... The study is structured as a series of interim reports. Interim Report IIIa, limited to the impacts of.... Comments are requested to assist in determining the level of analysis and impacts to be considered for...

Approval Summary: Letrozole (Femara® Tablets) for Adjuvant and Extended Adjuvant Postmenopausal Breast Cancer Treatment: Conversion of Accelerated to Full Approval

PubMed Central

Johnson, John R.; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor–positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76–1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen. PMID:22089970

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval.

PubMed

Cohen, Martin H; Johnson, John R; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.

78 FR 57257 - Medicare Determinations and Income-Related Monthly Adjustment Amounts to Medicare Part B Premiums...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

...; Conforming Changes to Regulations AGENCY: Social Security Administration. ACTION: Interim final rule with... monthly adjustment amounts (IRMAA) in order to conform to changes made to the Social Security Act (Act) by... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404 and 418 [Docket No. SSA-2012-0011] RIN 0960-AH47...

24 CFR 960.257 - Family income and composition: Regular and interim reexaminations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... appropriate adjustments in the rent after consultation with the family and upon verification of the... determine compliance once each twelve months with community service and self-sufficiency requirements in...

76 FR 14568 - Federal Acquisition Regulation; Use of Commercial Services Item Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

...-AL44 Federal Acquisition Regulation; Use of Commercial Services Item Authority AGENCIES: Department of... interim rule amending the Federal Acquisition Regulation (FAR) to implement section 868 of the Duncan... interim rule. II. Discussion/Analysis The analysis of public comments by the Defense Acquisition...

Japanese study of tofogliflozin with type 2 diabetes mellitus patients in an observational study of the elderly (J-STEP/EL): A 12-week interim analysis.

PubMed

Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Kameda, Hiroyuki; Tamura, Masahiro; Mihara, Hanako; Kaku, Kohei

2016-09-01

Sodium-glucose co-transporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, but are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing surveillance of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus and here report the results of a 12-week interim analysis, focusing on adverse drug reactions of special interest. The present prospective observational study included all type 2 diabetes mellitus patients aged ≥65 years who started tofogliflozin during the first 3 months after its launch. Data on demographic and baseline characteristics, clinical course and adverse events were collected. Of 1,535 patients registered, 1,506 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis at 12 weeks. A total of 178 of 1,506 patients (11.82%) had at least one adverse drug reaction to tofogliflozin. The incidence of adverse drug reactions of special interest (polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, skin disorders and hypoglycemia) was 2.19, 2.32, 1.33, 1.13, 1.46 and 0.73%, respectively. No new safety concerns were identified. Among those evaluable for clinical effectiveness, the mean (standard deviation) glycated hemoglobin decreased from 7.65% (1.35%) at baseline to 7.25% (1.16%) at 12 weeks by 0.39% (0.94%; P < 0.0001). This interim analysis characterized the safety profile of tofogliflozin in Japanese elderly patients with type 2 diabetes mellitus during the early post-marketing period. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial.

PubMed

Aggarwal, Swati P; Zinman, Lorne; Simpson, Elizabeth; McKinley, Jane; Jackson, Katherine E; Pinto, Hanika; Kaufman, Petra; Conwit, Robin A; Schoenfeld, David; Shefner, Jeremy; Cudkowicz, Merit

2010-05-01

In a pilot study, lithium treatment slowed progression of amyotrophic lateral sclerosis (ALS). We aimed to confirm or disprove these findings by assessing the safety and efficacy of lithium in combination with riluzole in patients with ALS. We did a double-blind, placebo-controlled trial with a time-to-event design. Between January and June, 2009, patients with ALS who were taking a stable dose of riluzole for at least 30 days were randomly assigned (1:1) by a centralised computer to receive either lithium or placebo. Patients, caregivers, investigators, and all site study staff with the exception of site pharmacists were masked to treatment assignment. The primary endpoint was the time to an event, defined as a decrease of at least six points on the revised ALS functional rating scale score or death. Interim analyses were planned for when 84 patients had been allocated treatment, 6 months later or after 55 events, and after 100 events. Analysis was by intention to treat. The stopping boundary for futility at the first interim analysis was a p value of at least 0.68. We used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. This trial is registered with ClinicalTrials.gov, NCT00818389. At the first interim analysis, 22 of 40 patients in the lithium group had an event compared with 20 of 44 patients in the placebo group (log rank p=0.51). The hazard ratio of reaching the primary endpoint was 1.13 (95% CI 0.61-2.07). The study was stopped at the first interim analysis because criterion for futility was met (p=0.78). The difference in mean decline in the ALS functional rating scale score between the lithium group and the placebo group was 0.15 (95% CI -0.43 to 0.73, p=0.61). There were no major safety concerns. Falls (p=0.04) and back pain (p=0.05) were more common in the lithium group than in the placebo group. We found no evidence that lithium in combination with riluzole slows progression of ALS more than riluzole alone. The time-to-event endpoint and use of prespecified interim analyses enabled a clear result to be obtained rapidly. This design should be considered for future trials testing the therapeutic efficacy of drugs that are easily accessible to people with ALS. National Institute of Neurological Disorders and Stroke, ALS Association, and ALS Society of Canada. Copyright 2010 Elsevier Ltd. All rights reserved.

Variations in return value estimate of ocean surface waves - a study based on measured buoy data and ERA-Interim reanalysis data

NASA Astrophysics Data System (ADS)

Muhammed Naseef, T.; Sanil Kumar, V.

2017-10-01

An assessment of extreme wave characteristics during the design of marine facilities not only helps to ensure their safety but also assess the economic aspects. In this study, return levels of significant wave height (Hs) for different periods are estimated using the generalized extreme value distribution (GEV) and generalized Pareto distribution (GPD) based on the Waverider buoy data spanning 8 years and the ERA-Interim reanalysis data spanning 38 years. The analysis is carried out for wind-sea, swell and total Hs separately for buoy data. Seasonality of the prevailing wave climate is also considered in the analysis to provide return levels for short-term activities in the location. The study shows that the initial distribution method (IDM) underestimates return levels compared to GPD. The maximum return levels estimated by the GPD corresponding to 100 years are 5.10 m for the monsoon season (JJAS), 2.66 m for the pre-monsoon season (FMAM) and 4.28 m for the post-monsoon season (ONDJ). The intercomparison of return levels by block maxima (annual, seasonal and monthly maxima) and the r-largest method for GEV theory shows that the maximum return level for 100 years is 7.20 m in the r-largest series followed by monthly maxima (6.02 m) and annual maxima (AM) (5.66 m) series. The analysis is also carried out to understand the sensitivity of the number of observations for the GEV annual maxima estimates. It indicates that the variations in the standard deviation of the series caused by changes in the number of observations are positively correlated with the return level estimates. The 100-year return level results of Hs using the GEV method are comparable for short-term (2008 to 2016) buoy data (4.18 m) and long-term (1979 to 2016) ERA-Interim shallow data (4.39 m). The 6 h interval data tend to miss high values of Hs, and hence there is a significant difference in the 100-year return level Hs obtained using 6 h interval data compared to data at 0.5 h interval. The study shows that a single storm can cause a large difference in the 100-year Hs value.

Interim Terrain Data (ITD) and Vector Product Interim Terrain Data (VITD) user's guide

DOT National Transportation Integrated Search

1996-09-01

This guide is intended to be a convenient reference for users of these types of terrain analysis data. ITD is a digitized version of the standard 1:50,000-scale tactical terrain analysis data base (TTADB) product produced by the Defense Mapping Agenc...

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial.

PubMed

Clark, Richard E; Polydoros, Fotios; Apperley, Jane F; Milojkovic, Dragana; Pocock, Christopher; Smith, Graeme; Byrne, Jenny L; de Lavallade, Hugues; O'Brien, Stephen G; Coffey, Tony; Foroni, Letizia; Copland, Mhairi

2017-07-01

Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4. We did this interim analysis of a non-randomised, phase 2 trial at 20 hospitals in the UK. We recruited patients (aged ≥18 years) with chronic myeloid leukaemia in first chronic phase who had received TKI for 3 years or more and were either in stable MR4 (BCR-ABL1:ABL1 ratio <0·01%; MR4 cohort) or in stable MMR (BCR-ABL1:ABL1 ratio consistently <0·1%) but not MR4 (MMR cohort) for 12 months or longer. Participants received half their standard TKI dose (imatinib 200 mg daily, dasatinib 50 mg daily, or nilotinib 200 mg twice daily) for 12 months. Molecular recurrence was defined as loss of MMR (BCR-ABL1:ABL1 ratio >0·1%) on two consecutive samples. The primary endpoint of this interim analysis was the proportion of patients who lost MMR on de-escalation and regained MMR on TKI resumption. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01804985. Between Dec 16, 2013 and April 10, 2015, we enrolled 174 patients into the MMR cohort (n=49) or the MR4 cohort (n=125). During the 12 months of half-dose therapy, 12 patients (7%) had molecular recurrence, all of whom regained MMR within 4 months of full-dose TKI resumption (median time to recovery 77 days). Recurrence was significantly lower in the MR4 cohort (three [2%; 90% CI 0·2-4·8] of 121 evaluable patients) than in the MMR cohort (nine [19%; 90% CI 9·5-28·0] of 48 evaluable patients; hazard ratio 0·12, 90% CI 0·04-0·37; p=0·0007), but was unrelated to previous TKI or TKI therapy duration. Adverse events (eg, lethargy, diarrhoea, rash, and nausea) improved during the first 3 months of de-escalation, though not thereafter. 16 serious adverse events were reported, including one fatality due to worsening pre-existing peripheral arterial occlusive disease in a patient who had received only imatinib. TKI de-escalation is safe for most patients with excellent responses to TKI therapy, and is associated with improvement in symptoms. These findings show that lower TKI doses might maintain responses in these patients, implying that such patients could be unnecessarily overtreated. Studies of more ambitious de-escalation are warranted. Newcastle University and Bloodwise. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

PubMed

Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

2017-08-01

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

National Home Start Evaluation Interim Report VI. Twelve-Month Program Issues, Outcomes and Costs.

ERIC Educational Resources Information Center

Goodrich, Nancy; And Others

This report assesses the progress of the six summative Home Start projects as evaluation families completed their first twelve months of enrollment. Home Start, a federally-funded 3-year (1972-1975) home-based demonstration program for low-income families with 3- to 5-year-old children was designed to enhance a mother's skills in dealing with her…

Residential Energy Consumption Survey (RECS): National interim energy consumption survey, 1978-1979, household monthly energy consumption and expenditures. Shopper's guide

NASA Astrophysics Data System (ADS)

Windell, P.

1981-08-01

The data from the National Interim Energy Consumption Survey (NIECS) is available to the public on machine readable magnetic tapes. Brief overviews of the Residential Energy Consumption Survey as a whole and of the NIECS in particular is a brief description of each of the files included in this tape, and a list of the variables in the data set are included. A copy of the fuel supplier record form used to collect consumption and expenditure data for each of the sample households is also included.

Determination of zenith hydrostatic delay and its impact on GNSS-derived integrated water vapor

NASA Astrophysics Data System (ADS)

Wang, Xiaoming; Zhang, Kefei; Wu, Suqin; He, Changyong; Cheng, Yingyan; Li, Xingxing

2017-08-01

Surface pressure is a necessary meteorological variable for the accurate determination of integrated water vapor (IWV) using Global Navigation Satellite System (GNSS). The lack of pressure observations is a big issue for the conversion of historical GNSS observations, which is a relatively new area of GNSS applications in climatology. Hence the use of the surface pressure derived from either a blind model (e.g., Global Pressure and Temperature 2 wet, GPT2w) or a global atmospheric reanalysis (e.g., ERA-Interim) becomes an important alternative solution. In this study, pressure derived from these two methods is compared against the pressure observed at 108 global GNSS stations at four epochs (00:00, 06:00, 12:00 and 18:00 UTC) each day for the period 2000-2013. Results show that a good accuracy is achieved from the GPT2w-derived pressure in the latitude band between -30 and 30° and the average value of 6 h root-mean-square errors (RMSEs) across all the stations in this region is 2.5 hPa. Correspondingly, an error of 5.8 mm and 0.9 kg m-2 in its resultant zenith hydrostatic delay (ZHD) and IWV is expected. However, for the stations located in the mid-latitude bands between -30 and -60° and between 30 and 60°, the mean value of the RMSEs is 7.3 hPa, and for the stations located in the high-latitude bands from -60 to -90° and from 60 to 90°, the mean value of the RMSEs is 9.9 hPa. The mean of the RMSEs of the ERA-Interim-derived pressure across at the selected 100 stations is 0.9 hPa, which will lead to an equivalent error of 2.1 mm and 0.3 kg m-2 in the ZHD and IWV, respectively, determined from this ERA-Interim-derived pressure. Results also show that the monthly IWV determined using pressure from ERA-Interim has a good accuracy - with a relative error of better than 3 % on a global scale; thus, the monthly IWV resulting from ERA-Interim-derived pressure has the potential to be used for climate studies, whilst the monthly IWV resulting from GPT2w-derived pressure has a relative error of 6.7 % in the mid-latitude regions and even reaches 20.8 % in the high-latitude regions. The comparison between GPT2w and seasonal models of pressure-ZHD derived from ERA-Interim and pressure observations indicates that GPT2w captures the seasonal variations in pressure-ZHD very well.

Experimental model: dye penetration of extensive interim restorations used during endodontic treatment while under load in a multiple axis chewing simulator.

PubMed

Jensen, Arna-Lee; Abbott, Paul V

2007-10-01

The purpose of this study was to design an experimental model that allowed extensive endodontic interim restorations to be tested for dye penetration while under simulated masticatory load. Extracted premolar teeth had standardized mesio-occluso-distal cavities prepared, and the root canals were instrumented. A cotton wool pellet was placed in the pulp chamber, and the cavities were restored with Cavit, IRM, Ketac-Fil Plus, Ketac-Silver, or composite resin (Z100). They were subjected to the equivalent of 3 months of clinical load while exposed to methylene blue dye. Results of this study could not support IRM as a suitable interim endodontic restorative material to use in extensive cavities. The dye penetration in the Ketac-Fil Plus and Ketac-Silver specimens was not predictable, and the results suggested Cavit and Z100 composite resin require further investigations as potentially useful materials for this purpose.

Pupil Inquiry Behavior Analysis and Change Activity. Interim Project Report.

ERIC Educational Resources Information Center

Manion, Raymond C.

This interim report discusses progress toward three major goals of the Pupil Inquiry Behavior Analysis and Change Activity: increased pupil inquiry, changed teacher behavior to facilitate pupil inquiry, and the development of a 32-week course of instruction to provide for these behavioral changes. Data currently available deals with the emotional…

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: Systematic review and meta-analysis.

PubMed

Adams, Hugo J A; Kwee, Thomas C

2016-10-01

This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study.

PubMed

Khandhar, Sandeep J; Bowling, Mark R; Flandes, Javier; Gildea, Thomas R; Hood, Kristin L; Krimsky, William S; Minnich, Douglas J; Murgu, Septimiu D; Pritchett, Michael; Toloza, Eric M; Wahidi, Momen M; Wolvers, Jennifer J; Folch, Erik E

2017-04-11

Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions. NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing. ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively. One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield. ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Interim analysis: A rational approach of decision making in clinical trial.

PubMed

Kumar, Amal; Chakraborty, Bhaswat S

2016-01-01

Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

Lanthanum carbonate: safety data after 10 years.

PubMed

Hutchison, Alastair J; Wilson, Rosamund J; Garafola, Svetlana; Copley, John Brian

2016-12-01

Despite 10 years of post-marketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium-like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5-year observational database study (SPD405-404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with lanthanum carbonate. Patients treated with lanthanum carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood-brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan-Meier analysis of SPD405-404 data from the United States Renal Data System revealed that the median 5-year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received lanthanum carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of lanthanum carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person-years of worldwide patient exposure, there is no evidence that lanthanum carbonate is associated with adverse safety outcomes in patients with end-stage renal disease. © 2016 Shire Development LLC. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.

Accounting for interim safety monitoring of an adverse event upon termination of a clinical trial.

PubMed

Dallas, Michael J

2008-01-01

Upon termination of a clinical trial that uses interim evaluations to determine whether the trial can be stopped, a proper statistical analysis must account for the interim evaluations. For example, in a group-sequential design where the efficacy of a treatment regimen is evaluated at interim stages, and the opportunity to stop the trial based on positive efficacy findings exists, the terminal p-value, point estimate, and confidence limits of the outcome of interest must be adjusted to eliminate bias. While it is standard practice to adjust terminal statistical analyses due to opportunities to stop for "positive" findings, adjusting due to opportunities to stop for "negative" findings is also important. Stopping rules for negative findings are particularly useful when monitoring a specific rare serious adverse event in trials designed to show safety with respect to the event. In these settings, establishing conservative stopping rules are appropriate, and therefore accounting for the interim monitoring can have a substantial effect on the final results. Here I present a method to account for interim safety monitoring and illustrate its usefulness. The method is demonstrated to have advantages over methodology that does not account for interim monitoring.

Modified Interim Mandibular Advancement (MIMA) Appliance for Symptomatic Correction of Obstructive Sleep Apnea

PubMed Central

Singh, Harpreet; Mishra, Harsh Ashok; Gupta, Ankur

2016-01-01

Obstructive Sleep Apnea (OSA) is a chronic, progressive, multifactorial, life-threatening disorder that causes significant impact on patient’s life. Patients with OSA [Apnea/Hypopnea Index (AHI)>30] who cannot tolerate Continuous Positive Airway Pressure (CPAP) therapy or are not surgical candidates may benefit from oral appliances. This paper describes interim appliance devised from existing Hawley’s retainer in patients with OSA. A 38-year-old man of athletic built with history of orthodontic treatment six months back due to esthetic concerns and wearing upper Hawley’s retainer, reported with chief complaint of frequent nocturnal awakening along with excessive daytime somnolence. Based on diagnostic aids, he was diagnosed with Class II Division 1 malocclusion with severe mandibular retrusion. Sleep test revealed AHI score of 34, suggestive of severe OSA. With ENT and Oral surgeon concurrence, mandibular advancement of 7mm with Bilateral Sagital Split Osteotomy (BSSO) with distraction was contemplated as a viable functional and curative stable treatment plan. Because of non-adherence and non-compliance with CPAP therapy and on request of patient, an interim anterior positioning appliance was devised to facilitate comfortable sound sleep till the time surgery is impending. After three months of wearing this customized appliance, improved quality of sleep was discernible; both subjectively as reported by patient and objectively using sleep test (AHI=9.8). PMID:27656589

Texturing of concrete pavements : interim report No. 1.

DOT National Transportation Integrated Search

1975-11-01

The scope of this report is to describe the results obtained during the first twelve-month period of this field research project. It includes the construction of test sections and the evaluation period after the project was opened to traffic. Each te...

40 CFR 142.22 - Review of State variances, exemptions and schedules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Review of...) Not later than 18 months after the effective date of the interim national primary drinking water... (and schedules prescribed pursuant thereto) by the States with primary enforcement responsibility...

Balloon or bougie for dilatation of benign oesophageal stricture? An interim report of a randomised controlled trial.

PubMed Central

Cox, J G; Winter, R K; Maslin, S C; Jones, R; Buckton, G K; Hoare, R C; Sutton, D R; Bennett, J R

1988-01-01

Seventy one patients with benign oesophageal strictures were randomised to receive balloon or bougie dilatation. Sixty five patients were eligible for analysis. At the end of five months the balloon group had significantly more dysphagia and the calibre of the strictures in the balloon group had narrowed by a greater degree. The methods were equally safe and acceptable to patients. While the choice of the method of dilatation depends on the individual patient's needs and operator experience, bougie dilatation is more effective in reducing dysphagia and maintaining stricture patency. Images Fig. 2 Fig. 3 PMID:3065156

Correlation between total precipitable water and precipitation over East Asia

NASA Astrophysics Data System (ADS)

Keum, Wangho; Lim, Gyu-Ho

2017-04-01

The precipitation rate(PR) and the total precipitable water(TPW) interact with various physical mechanisms. The correlation of two variables changes with difference of domain resolution and characteristics of the region. This poster analyzes the correlation between PR and TPW over East Asia using Cyclostationary Empirical Orthogonal Function(CSEOF) which is one of the PCA analysis. The CSEOF is useful to search a periodic pattern of the data. The anomalies which is subtracted climatological mean from the original data are used to represent annual cycles. Two variances of ERA-Interim Monthly Total Column Water vapor and GPCP monthly precipitation amounts with 372 time since January, 1984 to December, 2014 are decomposed into several modes separately. The first mode which explain largest variance are used in analysis. PC of both PR and TPW increase recently on mean value and amplitude, and they show considerable correlation on phase. The correlation coefficient of PR and TPW is 0.61 and maintains the same values by month. The result of harmonic analysis shows 2 to 6 year oscillations. As result of decomposed modes of two variables, there is the relationship between TPW PC series and horizontal moisture gradient. The Horizontal moist gradient can change affect moisture flux convergence which is one of important variable of rainfall events.

Efficacy of cranberry in prevention of urinary tract infection in a susceptible pediatric population.

PubMed

Foda, M M; Middlebrook, P F; Gatfield, C T; Potvin, G; Wells, G; Schillinger, J F

1995-01-01

The objective of the study was to evaluate liquid cranberry products as prophylaxis against bacterial urinary tract infection in a pediatric neuropathic bladder population. Forty cases managed by clean intermittent catheterization with or without pharmacotherapy were enrolled in a randomized single-blind cross-over study. Subjects ingested 15 mL/kg/day of cranberry cocktail or water for six months followed by the reverse for another six months. Initial catheter urine samples and subsequent monthly and interim cultures were obtained. Associated symptoms were recorded along with follow-up attendance/compliance registry. The number of negative culture months to the number of months contributed was tabulated and compared between interventions. Individual, cumulative and antimicrobial subset analysis was performed. Twenty one patients completed the study;12 dropped out for reasons related to the cranberry (taste, caloric load and cost); seven patients dropped out for other reasons (parents too busy, death, no stated reason). Wilcoxon matched-pairs Signed-ranks analysis revealed no difference between intervention periods (2-tailed P=.5566 [whole group]; p=.2845 [antimicrobial subset]) with respect to infection. Fewer infections were observed in nine patients taking cranberry juice and in nine patients given water; no difference was noted in three. Liquid cranberry products, on a daily basis, at the dosage employed, did not have any effect greater than that of water in preventing urinary tract infections in this pediatric neuropathic bladder population.

Analysis of Transportation Options for Commercial Spent Fuel in the U.S.

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

Kalinina, Elena; Busch, Ingrid Karin

The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S.more » Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage The U.S. Department of Energy (DOE) is laying the groundwork for implementing interim storage and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF) and high and associated transportation of spent nuclear fuel (SNF) high and associated transportation of spent nuclear fuel (SNF) highand associated transportation of spent nuclear fuel (SNF)...« less

Looking into the Future.

ERIC Educational Resources Information Center

McDowell, Stirling

1984-01-01

After four months of public hearings, the MacDonald Commission established to look into Canada's future is now preparing its interim report. The 220,000-member Canadian Teachers' Federation has submitted a four-point proposal to the commission calling for a reaffirmation of the overriding importance of education. (JBM)

Interim report deliverable 3.2 : focus group management process of the restricted use technology study

DOT National Transportation Integrated Search

2005-09-30

The Altarum Institute, under contract to the Michigan Department of Transportation (MDOT), currently is engaged in a project called the Altarum Restricted Use Technology Study. This study, an 18-month effort, seeks to apply restricted use techn...

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial.

PubMed

Frank, Jonathan M; Kayupov, Erdan; Moric, Mario; Segreti, John; Hansen, Erik; Hartman, Curtis; Okroj, Kamil; Belden, Katherine; Roslund, Brian; Silibovsky, Randi; Parvizi, Javad; Della Valle, Craig J

2017-01-01

Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation. (1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection? Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group. Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087). This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time. Level I, therapeutic study.

Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2-17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study.

PubMed

Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Jimeno, José; Villarreal, Ana Cecilia; Dato, Epiphany; Mazara, Sonia; Vargas, Maria; Brose, Manja; Rauscher, Martina; Tuboi, Suely; Borkowski, Astrid; Wallace, Derek

2018-02-01

Development of vaccines that are effective against all four dengue virus serotypes (DENV-1-4) in all age groups is important. Here, we present 18-month interim data from an ongoing study undertaken to assess the immunogenicity and safety of Takeda's tetravalent dengue vaccine (TDV) candidate over 48 months in children living in dengue-endemic countries. We undertook a phase 2, multicentre, randomised, double-blind, placebo-controlled study at three sites in the Dominican Republic, Panama, and the Philippines. We randomly assigned children aged 2-17 years to receive either two TDV doses 3 months apart (group 1), one TDV dose (group 2), one TDV dose and a booster dose 1 year later (group 3), or placebo (group 4). We did the randomisation (1:2:5:1) using an interactive web response system stratified by age. The primary endpoint of this 18-month interim analysis was DENV serotype-specific antibody geometric mean titres (GMTs) in the per-protocol immunogenicity subset on days 1, 28, 91, 180, 365, 393, and 540. Secondary safety endpoints were the proportions of participants with serious adverse events and with virologically confirmed dengue in the safety set, and solicited and unsolicited adverse events in the immunogenicity subset. This trial is registered with ClinicalTrials.gov, number NCT02302066. Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to group 1 (n=201), group 2 (n=398), group 3 (n=1002), and group 4 (n=199). 1794 participants received at least one dose of TDV or placebo (safety set), of whom 562 participated in the immunogenicity subset and 509 were included in the per-protocol set. Antibody titres remained elevated 18 months after vaccination in all TDV groups. At day 540, in groups 1, 2, 3, and 4, respectively, DENV-1 GMTs were 476 (95% CI 286-791), 461 (329-647), 1056 (804-1388), and 92 (49-173); DENV-2 GMTs were 1212 (842-1744), 1242 (947-1628), 1457 (1182-1796), and 177 (93-337); DENV-3 GMTs were 286 (171-478), 298 (205-433), 548 (411-730), and 78 (44-137); and DENV-4 GMTs were 98 (65-150), 102 (75-139), 172 (133-222), and 33 (21-52). Limited differences in GMTs were observed between groups 1 and 2 (in which participants received one and two doses of TDV, respectively). In baseline-seronegative participants, a 1-year booster clearly increased GMTs. Vaccine-related unsolicited adverse events occurred in 14 (2%) of 562 participants, but no vaccine-related serious adverse events arose. Symptomatic, virologically confirmed dengue was recorded in 21 (1·3%) of 1596 participants vaccinated with TDV compared with nine (4·5%) of 198 placebo recipients. TDV was well tolerated and immunogenic against all four dengue serotypes, irrespective of baseline dengue serostatus. These data provide proof of concept for TDV and support the ongoing phase 3 efficacy assessment of two doses 3 months apart. Takeda Vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interim Methadone and Patient Navigation in Jail: Rationale and Design of a Randomized Clinical Trial

PubMed Central

Schwartz, Robert P.; Kelly, Sharon M.; Mitchell, Shannon G.; Dunlap, Laura; Zarkin, Gary A.; Sharma, Anjalee; O’Grady, Kevin E.; Jaffe, Jerome H.

2016-01-01

Background Methadone maintenance is an effective treatment for opioid dependence but is rarely initiated in US jails. Patient navigation is a promising approach to improve continuity of care but has not been tested in bridging the gap between jail- and community-based drug treatment programs. Methods This is an open-label randomized clinical trial among 300 adult opioid dependent newly-arrested detainees that will compare three treatment conditions: methadone maintenance without routine counseling (termed Interim Methadone; IM) initiated in jail v. IM and patient navigation v. enhanced treatment-as-usual. The two primary outcomes will be: (1) the rate of entry into treatment for opioid use disorder within 30 days from release and (2) frequency of opioid positive urine tests over the 12-month follow-up period. An economic analysis will examine the costs, cost-effectiveness, and cost-benefit ratio of the study interventions. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions Given the large number of opioid dependent detainees in the US and elsewhere, initiating IM at the time of incarceration could be a significant public health and clinical approach to reducing relapse, recidivism, HIV-risk behavior, and criminal behavior. An economic analysis will be conducted to assist policy makers in determining the utility of adopting this approach. PMID:27282117

Interim methadone and patient navigation in jail: Rationale and design of a randomized clinical trial.

PubMed

Schwartz, Robert P; Kelly, Sharon M; Mitchell, Shannon G; Dunlap, Laura; Zarkin, Gary A; Sharma, Anjalee; O'Grady, Kevin E; Jaffe, Jerome H

2016-07-01

Methadone maintenance is an effective treatment for opioid dependence but is rarely initiated in US jails. Patient navigation is a promising approach to improve continuity of care but has not been tested in bridging the gap between jail- and community-based drug treatment programs. This is an open-label randomized clinical trial among 300 adult opioid dependent newly-arrested detainees that will compare three treatment conditions: methadone maintenance without routine counseling (termed Interim Methadone; IM) initiated in jail v. IM and patient navigation v. enhanced treatment-as-usual. The two primary outcomes will be: (1) the rate of entry into treatment for opioid use disorder within 30days from release and (2) frequency of opioid positive urine tests over the 12-month follow-up period. An economic analysis will examine the costs, cost-effectiveness, and cost-benefit ratio of the study interventions. We describe the background and rationale for the study, its aims, hypotheses, and study design. Given the large number of opioid dependent detainees in the US and elsewhere, initiating IM at the time of incarceration could be a significant public health and clinical approach to reducing relapse, recidivism, HIV-risk behavior, and criminal behavior. An economic analysis will be conducted to assist policy makers in determining the utility of adopting this approach. ClinicalTrials.gov: NCT02334215. Copyright © 2016 Elsevier Inc. All rights reserved.

40 CFR 142.22 - Review of State variances, exemptions and schedules.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Review of...) Not later than 18 months after the effective date of the interim national primary drinking water... scientific matters bearing on such variances and exemptions), and (2) advise of the opportunity to submit...

A review and update of the Virginia Department of Transportation's cash flow forecasting model : interim report.

DOT National Transportation Integrated Search

1995-01-01

The Virginia Department of Transportation uses a cash flow forecasting model to predict operations expenditures by month. Components of this general forecasting model estimate line items in the VDOT budget. The cash flow model was developed in the ea...

Cost Sensitivity Analysis for Consolidated Interim Storage of Spent Fuel: Evaluating the Effect of Economic Environment Parameters

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

Cumberland, Riley M.; Williams, Kent Alan; Jarrell, Joshua J.

This report evaluates how the economic environment (i.e., discount rate, inflation rate, escalation rate) can impact previously estimated differences in lifecycle costs between an integrated waste management system with an interim storage facility (ISF) and a similar system without an ISF.

78 FR 48503 - Proposed Revision to Missiles Generated by Extreme Winds

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

...-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants: LWR..., ``Design-Basis Hurricane and Hurricane Missiles for Nuclear Power Plants,'' and Interim Staff Guidance DC... and Hurricane Missiles for Nuclear Power Plants'' (ADAMS, Accession No. ML110940300), and Interim...

A web-based endpoint adjudication system for interim analyses in clinical trials.

PubMed

Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis

2009-02-01

A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However, once these issues were resolved, the reviewers found the system user-friendly and easy to navigate. Web-based data adjudication depends upon expeditious data collection and verification. Further, ability to use web-based technologies, in addition to clinical expertise, must be considered in selecting EAC members. The automated nature of this system makes it a practical mechanism for ensuring timely endpoint adjudication. The authors believe a similar approach could be useful for handling endpoint adjudication for future clinical trials.

A phase II flexible screening design allowing for interim analysis and comparison with historical control.

PubMed

Wu, Wenting; Bot, Brian; Hu, Yan; Geyer, Susan M; Sargent, Daniel J

2013-07-01

Sargent and Goldberg [1] proposed a randomized phase II flexible screening design (SG design) which took multiple characteristics of candidate regimens into consideration in selecting a regimen for further phase III testing. In this paper, we extend the SG design by including provisions for an interim analysis and/or a comparison to a historical control. By including a comparison with a historical control, a modified SG design not only identifies a more promising treatment but also assures that the regimen has a clinically meaningful level of efficacy as compared to a historical control. By including an interim analysis, a modified SG design could reduce the number of patients exposed to inferior treatment regimens. When compared to the original SG design, the modified designs increase the sample size moderately, but expand the utility of the flexible screening design substantially. Copyright © 2013 Elsevier Inc. All rights reserved.

Re-use of pilot data and interim analysis of pivotal data in MRMC studies: a simulation study

NASA Astrophysics Data System (ADS)

Chen, Weijie; Samuelson, Frank; Sahiner, Berkman; Petrick, Nicholas

2017-03-01

Novel medical imaging devices are often evaluated with multi-reader multi-case (MRMC) studies in which radiologists read images of patient cases for a specified clinical task (e.g., cancer detection). A pilot study is often used to measure the effect size and variance parameters that are necessary for sizing a pivotal study (including sizing readers, non-diseased and diseased cases). Due to the practical difficulty of collecting patient cases or recruiting clinical readers, some investigators attempt to include the pilot data as part of their pivotal study. In other situations, some investigators attempt to perform an interim analysis of their pivotal study data based upon which the sample sizes may be re-estimated. Re-use of the pilot data or interim analyses of the pivotal data may inflate the type I error of the pivotal study. In this work, we use the Roe and Metz model to simulate MRMC data under the null hypothesis (i.e., two devices have equal diagnostic performance) and investigate the type I error rate for several practical designs involving re-use of pilot data or interim analysis of pivotal data. Our preliminary simulation results indicate that, under the simulation conditions we investigated, the inflation of type I error is none or only marginal for some design strategies (e.g., re-use of patient data without re-using readers, and size re-estimation without using the effect-size estimated in the interim analysis). Upon further verifications, these are potentially useful design methods in that they may help make a study less burdensome and have a better chance to succeed without substantial loss of the statistical rigor.

Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients

PubMed Central

2013-01-01

Background This study is to evaluate the predictive value of FDG-PET (PET) in pediatric and adolescent patients suffering from non-Hodgkin lymphoma (pNHL) in comparison to information provided by conventional imaging methods (CIM). Methods Imaging was performed at baseline and at interim (after 2 cycles of chemotherapy). The response assessment in PET was carried out visually and semi-quantitatively, the latter one by use of percentage decrease in SUVmax from baseline to interim (ΔSUVmax). The PET-based results were compared to the findings by CIM. Progression-free survival (PFS) was analyzed using Kaplan-Meier curves (KM) and log-rank test. Results The final study included 16 patients (mean follow-up time, 60.2 months (range, 4.0 to 85.7 months)). Relapse occurred in four patients. Visual PET compared to CIM revealed higher sensitivity (3/4 vs 1/4) and NPV (6/7 vs 10/13), and equal PPV (3/9 vs 1/3), but lower specificity (6/12 vs 10/12) and accuracy (9/16 vs 11/16). False-positive findings in PET at interim were predominantly observed in patients presenting bulky disease (5/6), whereas CIM was true-negative in all of these cases. KM analyses revealed no significant differences in 5-year PFS neither for CIM (76.9% vs 66.7%; p = 0.67) nor for visual PET (85.7% vs 66.7%; p = 0.34) nor for ΔSUVmax (88.9% vs 57.1%; p = 0.12). Conclusions The predictive value of iPET in pediatric patients suffering from NHL was limited due to considerably high amount of false-positive findings, especially in patients suffering from bulky disease. However, due to our limited sample size, final conclusions cannot be drawn and, thus, call for further evaluation of PET in pNHL in larger and more homogenous patient series. PMID:24139528

Stability of Beriplast P fibrin sealant: storage and reconstitution.

PubMed

Eberhard, Ulrich; Broder, Martin; Witzke, Günther

2006-04-26

This study was performed to investigate the stability of Beriplast P fibrin sealant (FS) across a range of storage conditions, both pre- and post-reconstitution. Storage stability of the FS was evaluated during long-term refrigeration (24 months) with or without interim storage at elevated temperatures (40 degrees C for 1 week and 25 degrees C for 1 and 3 months). Stability of individual FS components was assessed by measuring: fibrinogen content, Factor XIII activity (FXIII), thrombin activity and aprotinin potency. The package integrity of each component was also checked (sterility testing, moisture content and pH). Storage stability was also evaluated by testing the reconstituted product for adhesion (tearing force testing after mixing the solutions) and sterility. Reconstitution stability was evaluated following 3-months' storage, for up to 50 h post-reconstitution using the same tests as for the storage stability investigations. Pre-defined specifications were met for fibrinogen content, Factor XIII activity, and thrombin activity, demonstrating storage stability. Package integrity and the functionality and sterility of the reconstituted product were confirmed throughout. Reconstitution stability was demonstrated for up to 50 h following reconstitution, in terms of both tearing force and sterility tests. In conclusion, the storage stability of Beriplast P was demonstrated over a range of 24-month storage schedules including interim exposure to elevated temperature, and the reconstituted product was stable for up to 50 h.

40 CFR 265.221 - Design and operating requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effective date of a prohibition pursuant to § 268.5 of this chapter, within this 48-month period. [50 FR... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... each replacement of an existing surface impoundment unit must install two or more liners, and a...

40 CFR 265.226 - Monitoring and inspection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... operating level for two consecutive months, the amount of liquids in the sumps must be recorded at least... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... period. (2) After the final cover is installed, the amount of liquids removed from each leak detection...

40 CFR 265.226 - Monitoring and inspection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... operating level for two consecutive months, the amount of liquids in the sumps must be recorded at least... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... period. (2) After the final cover is installed, the amount of liquids removed from each leak detection...

40 CFR 265.221 - Design and operating requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... effective date of a prohibition pursuant to § 268.5 of this chapter, within this 48-month period. [50 FR... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... each replacement of an existing surface impoundment unit must install two or more liners, and a...

40 CFR 265.221 - Design and operating requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... effective date of a prohibition pursuant to § 268.5 of this chapter, within this 48-month period. [50 FR... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... each replacement of an existing surface impoundment unit must install two or more liners, and a...

40 CFR 265.226 - Monitoring and inspection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... operating level for two consecutive months, the amount of liquids in the sumps must be recorded at least... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... period. (2) After the final cover is installed, the amount of liquids removed from each leak detection...

40 CFR 265.221 - Design and operating requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... effective date of a prohibition pursuant to § 268.5 of this chapter, within this 48-month period. [50 FR... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... each replacement of an existing surface impoundment unit must install two or more liners, and a...

40 CFR 265.112 - Closure plan; amendment of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND.... By May 19, 1981, or by six months after the effective date of the rule that first subjects a facility... description of other activities necessary during the partial and final closure periods to ensure that all...

40 CFR 265.226 - Monitoring and inspection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... operating level for two consecutive months, the amount of liquids in the sumps must be recorded at least... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... period. (2) After the final cover is installed, the amount of liquids removed from each leak detection...

40 CFR 265.221 - Design and operating requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... effective date of a prohibition pursuant to § 268.5 of this chapter, within this 48-month period. [50 FR... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... each replacement of an existing surface impoundment unit must install two or more liners, and a...

40 CFR 265.226 - Monitoring and inspection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... operating level for two consecutive months, the amount of liquids in the sumps must be recorded at least... (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND... period. (2) After the final cover is installed, the amount of liquids removed from each leak detection...

Wide-bandwidth high-resolution search for extraterrestrial intelligence

NASA Technical Reports Server (NTRS)

Horowitz, Paul

1992-01-01

This interim report summarizes the research accomplished during the initial 6-month period of the grant. Activities associated with antenna configurations, the channelizing downconverter, the fast Fourier transform array, the DSP (digital signal processing) array, and the backend and UNIX workstation are discussed. Publications submitted during the reporting period are listed.

EARLY TRAINING PROJECT. INTERIM REPORT.

ERIC Educational Resources Information Center

GRAY, SUSAN W.; KLAUS, RUPERT A.

THE EARLY TRAINING PROJECT ATTEMPTED TO IMPROVE THE INTELLECTUAL FUNCTIONING AND PERSONAL ADJUSTMENT OF CULTURALLY DISADVANTAGED CHILDREN THROUGH SPECIAL EXPERIENCES IN THE 15- OR 24-MONTHS PRECEDING FIRST GRADE AND IN THE FIRST YEAR OF SCHOOL. THE PROCEDURES OF THE PROJECT CONSISTED OF TWO TRAINING SEQUENCES. THE FIRST SEQUENCE INVOLVED TWO…

CNN Newsroom Classroom Guides, February 2002.

ERIC Educational Resources Information Center

Cable News Network, Atlanta, GA.

These classroom guides, designed to accompany the daily CNN (Cable News Network) Newsroom broadcasts for the month of February 2002, provide program rundowns, suggestions for class activities and discussion, student handouts, and a list of related news terms. Top stories include: Afghanistan's interim leader is making a global impression (February…

Altarum restricted use technology study : interim report, deliverable 3.1 : list of invitees for the focus group

DOT National Transportation Integrated Search

2005-09-01

This study, an 18-month effort, seeks to apply restricted use technology to the mandates of MDOT. For Deliverable 3.1 described in the Work Plan governing the Altarum Restricted Use Technology Study, the Altarum project team is required to provide a ...

75 FR 75884 - Regulations Regarding Income-Related Monthly Adjustment Amounts to Medicare Beneficiaries...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... premiums. This new subpart implements changes made to the Social Security Act (Act) by the Affordable Care... SOCIAL SECURITY ADMINISTRATION 20 CFR Part 418 [Docket No. SSA-2010-0029] RIN 0960-AH22... Coverage Premiums AGENCY: Social Security Administration. ACTION: Interim final rule with request for...

14 CFR 1274.933 - Summary of recipient reporting responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... bar exists, otherwise within 2 years 1274.913 Patent Rights—Retention by the Recipient (Small Business... As required 1274.911 Patent Rights(Paragraph (b)(4)) Interim Report of Reportable Items Every 12 months 1274.912 Patent Rights—Retention by the Recipient (Large Business)(Paragraph (e)(3)(i)) Final...

Conditional power and predictive power based on right censored data with supplementary auxiliary information.

PubMed

Sun, Libo; Wan, Ying

2018-04-22

Conditional power and predictive power provide estimates of the probability of success at the end of the trial based on the information from the interim analysis. The observed value of the time to event endpoint at the interim analysis could be biased for the true treatment effect due to early censoring, leading to a biased estimate of conditional power and predictive power. In such cases, the estimates and inference for this right censored primary endpoint are enhanced by incorporating a fully observed auxiliary variable. We assume a bivariate normal distribution of the transformed primary variable and a correlated auxiliary variable. Simulation studies are conducted that not only shows enhanced conditional power and predictive power but also can provide the framework for a more efficient futility interim analysis in terms of an improved accuracy in estimator, a smaller inflation in type II error and an optimal timing for such analysis. We also illustrated the new approach by a real clinical trial example. Copyright © 2018 John Wiley & Sons, Ltd.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

PubMed Central

Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

2017-01-01

Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration ClinicalTrials.gov NCT01310738 PMID:28662034

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

PubMed

Martín, M; Chan, A; Dirix, L; O'Shaughnessy, J; Hegg, R; Manikhas, A; Shtivelband, M; Krivorotko, P; Batista López, N; Campone, M; Ruiz Borrego, M; Khan, Q J; Beck, J T; Ramos Vázquez, M; Urban, P; Goteti, S; Di Tomaso, E; Massacesi, C; Delaloge, S

2017-02-01

Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II. © 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.

The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma.

PubMed

Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-07-01

The aim of the present study was to assess the value of interim 18 F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy. The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18 F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients' best clinical response, assessed at a median of 21.4 months (range 6.3-41.9 months) was used as reference. According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46). The application of the recently proposed PERCIMT to interim 18 F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.

Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

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

Halasz, Lia M.; Jacene, Heather A.; Catalano, Paul J.

2012-08-01

Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT.more » Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.« less

Conditional estimation using prior information in 2-stage group sequential designs assuming asymptotic normality when the trial terminated early.

PubMed

Shimura, Masashi; Maruo, Kazushi; Gosho, Masahiko

2018-04-23

Two-stage designs are widely used to determine whether a clinical trial should be terminated early. In such trials, a maximum likelihood estimate is often adopted to describe the difference in efficacy between the experimental and reference treatments; however, this method is known to display conditional bias. To reduce such bias, a conditional mean-adjusted estimator (CMAE) has been proposed, although the remaining bias may be nonnegligible when a trial is stopped for efficacy at the interim analysis. We propose a new estimator for adjusting the conditional bias of the treatment effect by extending the idea of the CMAE. This estimator is calculated by weighting the maximum likelihood estimate obtained at the interim analysis and the effect size prespecified when calculating the sample size. We evaluate the performance of the proposed estimator through analytical and simulation studies in various settings in which a trial is stopped for efficacy or futility at the interim analysis. We find that the conditional bias of the proposed estimator is smaller than that of the CMAE when the information time at the interim analysis is small. In addition, the mean-squared error of the proposed estimator is also smaller than that of the CMAE. In conclusion, we recommend the use of the proposed estimator for trials that are terminated early for efficacy or futility. Copyright © 2018 John Wiley & Sons, Ltd.

Executive Director Fred Spilhaus Steps Down; Interim Leader Takes AGU Reins

NASA Astrophysics Data System (ADS)

Weiss, Peter

2009-02-01

After 39 years as AGU executive director, Fred Spilhaus has stepped down from his post; he will become executive director emeritus. At a 27 January 2009 staff meeting at AGU headquarters, in Washington, D. C., three of the Union officers introduced Robert T. Van Hook, who will serve as interim executive director while AGU conducts a worldwide search for a new executive director. The search is expected to start in the summer of 2009 and to take from 6 to 18 months. ``AGU is a growing, vibrant organization that wishes to thoughtfully chart its course for the coming decades,'' Van Hook said. ``I am a professional interim executive, here to build on Fred Spilhaus's legacy. I want to help this extraordinary Union of researchers, teachers, and students take careful stock of where it is today, where it wants to go tomorrow, and what kind of staff leader it needs to help it get there,'' he said. ``My job is to get you ready for the next executive director,'' Van Hook told AGU staff, noting that he is not a candidate for the position himself.

IMPACT ON SURVIVAL OF 12 VERSUS 3 MONTHLY CYCLES OF PACLITAXEL (175 MG/M2) ADMINISTERED TO PATIENTS WITH ADVANCED OVARIAN CANCER WHO ATTAINED A COMPLETE RESPONSE TO PRIMARY PLATINUM-PACLITAXEL: FOLLOW-UP OF A SOUTHWEST ONCOLOGY GROUP AND GYNECOLOGIC ONCOLOGY GROUP PHASE 3 TRIAL

PubMed Central

Markman, Maurie; Liu, PY; Moon, James; Monk, Bradley J.; Copeland, Larry; Wilczynski, Sharon; Alberts, David

2009-01-01

Objectives A SWOG/GOG phase 3 trial exploring the impact of 12-monthly cycles of paclitaxel given to patients with advanced ovarian cancer who achieved a complete response to primary chemotherapy was discontinued by the Data Safety and Monitoring Committee when a prospectively-defined interim analysis revealed a highly statistically significant improvement in progression-free survival (PFS). At study closure, it was too early to assess the impact on overall survival. Methods Patients (n = 296) received either 3 or 12 monthly cycles of paclitaxel (175 mg/m2 over 3-hours). Results Of the 146 patients on the 3-cycle arm, 9 (6%) received > 3-cycles. Median (12 versus 3 cycle; intention-to-treat analysis) updated PFS (all pts) 22 versus 14 months, p=0.006; overall survival (all pts) 53 versus 48 months, p=0.34. Conclusion Twelve cycles of single agent maintenance paclitaxel significantly improves PFS. Explanations for the lack of a favorable influence on overall survival include: (a) treatment at relapse equalized outcome; (b) the sample size was insufficient to reveal a difference; (c) “crossover” of patients from 3 cycles to longer treatment masked a potential difference. An ongoing phase 3 trial will hopefully provide a definitive answer to the question of the impact of this maintenance strategy on overall survival. PMID:19447479

A Translational Approach to Validate in Vivo Anti-tumor Effects of Chloroquine on Breast Cancer Risk

DTIC Science & Technology

2014-05-01

performed at one month post- activation to ensure appropriate accruals with the sampling method, Respondent Driven Sampling (RDS), was encouraging...Add another country/ year of service *Repeat these questions as many times as the RPCV has tours of service. Are you currently active duty...chains.  Interim  analyses  were  performed  at  one  and  two  months  post-­‐ activation  to  ensure  appropriate

Medical examination of Rongelap people six months after exposure to fallout

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

Bond, V.P.; Conard, R.A.; Robertson, J.S.

1955-04-01

Follow-up medical examinations were made of the Marshallese inhabitants of Rongelap Atoll 6 months after they had been exposed to atomic bomb fallout radiation during the Operation CASTLE test series in March, 1954. During the early acute period following exposure, these people had shown systemic effects and marked hematological changes resulting from penetrating gamma radiation; extensive superficial skin lesions and epilation associated principally with beta and soft gamma radiation from fallout material deposited on uncovered skin areas; and minimal internal contamination with fission products, resulting principally from ingestion of fallout material. At the time of the 6-month resurvey the individuals,more » in general, appeared healthy and normally active, and no deaths had occurred in the interim period. Chest X-rays of all individuals revealed no abnormalities ascribable to the fallout radiation. Analysis of hematological data obtained failed to demonstrate a significant effect of measles on the peripheral blood count. Neutrophile, lymphocyte, and platelet counts were not significantly different from counts taken on the 74th post-exposure day, and none of these values had returned to control levels.« less

Precipitation Seasonality over the Indian Subcontinent: Assessment of Gauge, Reanalyses and Satellite Products

NASA Astrophysics Data System (ADS)

Renwick, J. A.; Rana, S.; McGregor, J.

2015-12-01

This work addresses the seasonal (winter, pre-monsoon, monsoon and post-monsoon) performance of seven precipitation products from three different data sources: gridded station data, satellite-derived data and reanalyses products over the Indian Subcontinent, for a period of 10 years (1997/98 to 2006/07). Precipitation products evaluated are the Asian Precipitation - Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE), the Climate Prediction Center unified gauge (CPC-uni), the Global Precipitation Climatology project (GPCP), Tropical Rainfall Measuring Mission (TRMM) post real-time research products (3B42-V6 and 3B42-V7), the Climate Forecast System Reanalysis (CFSR) and the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim). Several verification measures are employed to assess the accuracy of the data. All datasets capture the large-scale characteristics of the seasonal mean precipitation distribution, albeit with pronounced seasonal and/or regional differences. Compared to APHRODITE, the gauge-only (CPC-uni) and the satellite-derived precipitation products (GPCP, 3B42-V6 and 3B42-V7) capture the summer monsoon rainfall variability better than CFSR and ERA-Interim. Similar conclusions were drawn for the post-monsoon season, with the exception of 3B42-V7, which underestimates post-monsoon precipitation. Over mountainous regions 3B42-V7 shows an appreciable improvement over 3B42-V6 and other gauge-based precipitation products. Significantly large biases/errors occur during the winter months, which is likely related to the uncertainty in observations that artificially inflate the existing error in reanalyses and satellite retrievals.

A Process Evaluation of Project Developmental Continuity. Interim Report VI: Executive Summary. Recommendations for Continuing the Impact Study.

ERIC Educational Resources Information Center

Granville, Arthur C.; Love, John M.

This brief report summarizes the analysis and conclusions presented in detail in Interim Report VI regarding the feasibility of conducting a longitudinal study of Project Developmental Continuity (PDC). This project is a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and…

Interim Assessment Data: A Case Study on Modifying Instruction Based on Benchmark Feedback

ERIC Educational Resources Information Center

Lange, Tracey M.

2014-01-01

The role of data analysis in the jobs of instructional leaders has become as commonplace as teachers creating lesson plans and taking roll in the classroom. Teachers and building leaders routinely use interim assessment data to develop thoughtful and robust instructional plans that address identified areas of student need. The link between the…

Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study).

PubMed

Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N

2012-07-15

The Step Study tested whether an adenovirus serotype 5 (Ad5)-vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03-1.92; P= .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P=1.0) over all follow-up time. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination.

48 CFR 1852.216-77 - Award fee for end item contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Contractor's performance for the entire contract will be evaluated to determine total earned award fee. No award fee or base fee will be paid to the Contractor if the final award fee evaluation is “poor... the Contractor's interim performance every 6* months to monitor Contractor performance prior to...

Back from the Brink: Harvard Gets it Right. Carnegie Perspectives

ERIC Educational Resources Information Center

Ehrlich, Tom

2007-01-01

Eighteen months after soundly criticizing a new Harvard general education that proposed to abandon the concept of a structured general education, substituting a minimum distribution requirement under which students could choose a few courses from hundreds offered by the faculty, the writer applauds the shift, encouraged by interim president Derek…

32 CFR 733.3 - Information and policy on support of dependents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... so would lend excessive credence to administrative tools which have been designed for use only within... armed forces). Interim support for each family member shall be either $200.00 per supported family... of 1/3 gross pay, per month. (4) Both spouses in the armed forces. (i) No children of the marriage...

Early Language Development in Blind and Severely Visually Impaired Children. Interim Report on Pilot Study.

ERIC Educational Resources Information Center

Moore, Vanessa; McConachie, Helen

This study investigated variables that might be associated with outcome differences in language development of 10 children (ages 10-20 months) with blindness or severe visual impairments, attending a developmental vision clinic in southern England. Subjects' early patterns of expressive language development were examined and related to observed…

14 CFR 60.21 - Interim qualification of FSTDs for new aircraft types or models.

Code of Federal Regulations, 2011 CFR

2011-01-01

... aircraft, even though the aircraft manufacturer's aircraft data package is preliminary, if the sponsor...) Within twelve months of the release of the final aircraft data package by the aircraft manufacturer, but... apply for initial qualification in accordance with § 60.15 based on the final aircraft data package...

14 CFR 60.21 - Interim qualification of FSTDs for new aircraft types or models.

Code of Federal Regulations, 2014 CFR

2014-01-01

... aircraft, even though the aircraft manufacturer's aircraft data package is preliminary, if the sponsor...) Within twelve months of the release of the final aircraft data package by the aircraft manufacturer, but... apply for initial qualification in accordance with § 60.15 based on the final aircraft data package...

14 CFR 60.21 - Interim qualification of FSTDs for new aircraft types or models.

Code of Federal Regulations, 2010 CFR

2010-01-01

... aircraft, even though the aircraft manufacturer's aircraft data package is preliminary, if the sponsor...) Within twelve months of the release of the final aircraft data package by the aircraft manufacturer, but... apply for initial qualification in accordance with § 60.15 based on the final aircraft data package...

14 CFR 60.21 - Interim qualification of FSTDs for new aircraft types or models.

Code of Federal Regulations, 2013 CFR

2013-01-01

... aircraft, even though the aircraft manufacturer's aircraft data package is preliminary, if the sponsor...) Within twelve months of the release of the final aircraft data package by the aircraft manufacturer, but... apply for initial qualification in accordance with § 60.15 based on the final aircraft data package...

14 CFR 60.21 - Interim qualification of FSTDs for new aircraft types or models.

Code of Federal Regulations, 2012 CFR

2012-01-01

... aircraft, even though the aircraft manufacturer's aircraft data package is preliminary, if the sponsor...) Within twelve months of the release of the final aircraft data package by the aircraft manufacturer, but... apply for initial qualification in accordance with § 60.15 based on the final aircraft data package...

An evaluation of the impact of the Virginia driver improvement program on negligent driving : 12-month report [interim report].

DOT National Transportation Integrated Search

1982-01-01

This study sought to evaluate the impact of the four basic treatment combinations of the rehabilitation component of the Virginia driver improvement program. It was found that receipt of a warning letter from the Division of Motor Vehicles had no eff...

EPA issues interim final waste minimization guidance

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

Bergeson, L.L.

1993-08-01

The U.S. Environmental Protection Agency (EPA) has released a new and detailed interim final guidance to assist hazardous waste generators in certifying they have a waste minimization program in place under the Resource Conservation and Recovery Act (RCRA). EPA's guidance identifies the basic elements of a waste minimization program in place that, if present, will allow people to certify they have implemented a program to reduce the volume and toxicity of hazardous waste to the extent economically practical. The guidance is directly applicable to generators of 1000 or more kilograms per month of hazardous waste, or large-quantity generators, and tomore » owners and operators of hazardous waste treatment, storage or disposal facilities who manage their own hazardous waste on site. Small-quantity generators that generate more than 100 kilograms, but less than 1,000 kilograms, per month of hazardous waste are not subject to the same program in place certification requirement. Rather, they must certify on their manifests that they have made a good faith effort to minimize their waste generation.« less

Predictors of functional level and quality of life at 6 months after a first-ever stroke: the KOSCO study.

PubMed

Chang, Won Hyuk; Sohn, Min Kyun; Lee, Jongmin; Kim, Deog Young; Lee, Sam-Gyu; Shin, Yong-Il; Oh, Gyung-Jae; Lee, Yang-Soo; Joo, Min Cheol; Han, Eun Young; Kang, Chung; Kim, Yun-Hee

2016-06-01

Predicting functional outcome and quality of life (QOL) is critical to the treatment of patients with stroke. The purpose of this study was to analyze the factors influencing functional status and QOL of stroke patients 6 months after a first-ever stroke. This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation Study, designed to include 10 years of follow-up for first-ever stroke patients. This study analyzed data from 2857 patients who completed face-to-face assessments with the functional independence measurement (FIM) and Euro Quality of Life-5D (EQ-5D) at 6 months after stroke onset. A multivariate regression analysis was used to analyze factors that potentially influenced FIM and EQ-5D results at 6 months after stroke. Of the patients in this study, 80.1 % suffered from ischemic stroke and 19.9 % experienced hemorrhagic stroke. The independent predictors of functional independency measured by FIM at 6 months after stroke were age, initial stroke severity, duration of hospitalization, and functional level at discharge in terms of motor, ambulation, and language. For QOL measured by EQ-5D at 6 months after stroke, age, duration of hospitalization, and motor function at discharge were significant predictors. In conclusion, proper treatment to achieve maximal functional gain at discharge may be an important factor in improving functional independency and QOL in chronic stage stroke survivors. These results provide useful information for establishing comprehensive and systematic care for stroke patients.

The skill of ECMWF long range Forecasting System to drive impact models for health and hydrology in Africa

NASA Astrophysics Data System (ADS)

Di Giuseppe, F.; Tompkins, A. M.; Lowe, R.; Dutra, E.; Wetterhall, F.

2012-04-01

As the quality of numerical weather prediction over the monthly to seasonal leadtimes steadily improves there is an increasing motivation to apply these fruitfully to the impacts sectors of health, water, energy and agriculture. Despite these improvements, the accuracy of fields such as temperature and precipitation that are required to drive sectoral models can still be poor. This is true globally, but particularly so in Africa, the region of focus in the present study. In the last year ECMWF has been particularly active through EU research founded projects in demonstrating the capability of its longer range forecasting system to drive impact modeling systems in this region. A first assessment on the consequences of the documented errors in ECMWF forecasting system is therefore presented here looking at two different application fields which we found particularly critical for Africa - vector-born diseases prevention and hydrological monitoring. A new malaria community model (VECTRI) has been developed at ICTP and tested for the 3 target regions participating in the QWECI project. The impacts on the mean malaria climate is assessed using the newly realized seasonal forecasting system (Sys4) with the dismissed system 3 (Sys3) which had the same model cycle of the up-to-date ECMWF re-analysis product (ERA-Interim). The predictive skill of Sys4 to be employed for malaria monitoring and forecast are also evaluated by aggregating the fields to country level. As a part of the DEWFORA projects, ECMWF is also developing a system for drought monitoring and forecasting over Africa whose main meteorological input is precipitation. Similarly to what is done for the VECTRI model, the skill of seasonal forecasts of precipitation is, in this application, translated into the capability of predicting drought while ERA-Interim is used in monitoring. On a monitoring level, the near real-time update of ERA-Interim could compensate the lack of observations in the regions. However, ERA-Interim suffers from biases and drifts that limit its application for drought monitoring purposes in some regions.

One-year clinical outcomes of BioMatrix™-Biolimus A9™ eluting stent: the e-BioMatrix multicenter post marketing surveillance registry in India.

PubMed

Mehta, Ashwin B; Chandra, Praveen; Dalal, Jamshed; Shetty, Prabhakar; Desai, Devang; Chocklingam, K; Prajapati, Jayesh; Kumar, Pramod; Magarkar, Vilas; Vasawada, Apurva; Goyal, B K; Kumar, Viveka; Rao, V Suryaprakash; Babu, Ramesh; Parikh, Pritesh; Kaul, Upendra; Patil, Aruna; Mhetre, Tushar; Rangnekar, Hrishikesh

2013-01-01

The e-BioMatrix is a post marketing multicenter registry with an objective to evaluate the 2 year clinical safety and efficacy outcomes in patients treated with BioMatrix™ - Biolimus A9™ (BA9™) drug eluting stents (DES). Drug-eluting stents still have late-stage disadvantages that might be attributable to the permanent polymer. BioMatrix a new generation DES containing anti-proliferative drug Biolimus A9™ incorporating a biodegradable abluminal coating that leaves a polymer-free stent after drug release enhancing strut coverage while preventing neointimal hyperplasia. This interim analysis consists of a total of 1189 patients with 1418 lesions treated with BioMatrix stent who entered this multicenter registry in India. We analyzed the incidence of major adverse cardiac events (MACE) and stent thrombosis (ST) at 1, 6, and 12 months with an extended follow-up of 2 years. Recommended antiplatelet regimen included clopidogrel and aspirin for 12 months. The mean age was 57.6 ± 10.9 years, 81.8% were males, comorbidity index was 1.20 ± 1.33, 68% presented with acute coronary syndrome, 49% had hypertension and 40.8% had diabetes mellitus. One-year clinical follow-up was completed in 987 patients at the time of interim analysis. The incidence of MACE is 0.45 for 1544 person-year follow-up. There were only 03 cases of ST (01 late ST) reported during this time. This registry demonstrates excellent one-year clinical safety and efficacy of BioMatrix stents. The 1-year result shows that BioMatrix stent may be a suitable alternative as compared to contemporary DESs which are currently available in the market for simple as well complex disease. Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

PubMed

Choueiri, Toni K; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul N; Rini, Brian I; Donskov, Frede; Hammers, Hans; Hutson, Thomas E; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J; Bjarnason, Georg A; Géczi, Lajos; Keam, Bhumsuk; Maroto, Pablo; Heng, Daniel Y C; Schmidinger, Manuela; Kantoff, Philip W; Borgman-Hagey, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M; Tannir, Nizar M; Motzer, Robert J

2015-11-05

Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate. Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).

A global validation of ERA-Interim integrated water vapor estimates using ground-based GNSS observations

NASA Astrophysics Data System (ADS)

Ahmed, F.; Dousa, J.; Hunegnaw, A.; Teferle, F. N.; Bingley, R.

2017-12-01

Integrated water vapor (IWV) derived from climate reanalysis models, such as the European Centre for Medium-range Weather Forecasts (ECMWF) ReAnalysis-Interim (ERA-Interim), is widely used in many atmospheric applications. Therefore, it is of interest to assess the quality of this reanalysis product using available observations. Observations from Global Navigation Satellite Systems (GNSS) are, as of now, available for a period of over 2 decades and their global availability makes it possible to validate the IWV obtained from climate reanalysis models in different geographical and climatic regions. In this study, primarily, three 5-year long homogeneously reprocessed GNSS-derived IWV datasets containing over 400 globally distributed ground-based GNSS stations have been used to validate the IWV estimates obtained from the ERA-Interim climate reanalysis model in 25 different climate zones. The IWV from ERA-Interim has been obtained by vertically integrating the specific humidity at all model levels above the locations of GNSS stations. It has been studied how the difference between the ERA-Interim IWV and the GNSS-derived IWV varies with respect to the different climate zones as well as with respect to the difference in the model orography and latitude. The results show a dependence of the ability of ERA-Interim to model the IWV on difference in climate types and latitude. This dependence, however, is dictated by the concentration of water vapor in different climate zones and at different latitudes. Furthermore, as a secondary focus of this study, the weighted mean atmospheric temperature (Tm) obtained from ERA-Interim has been compared to its equivalent obtained using two widely used approximations globally.

Interim reliability-evaluation program: analysis of the Browns Ferry, Unit 1, nuclear plant. Appendix C - sequence quantification

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

Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

1982-07-01

This report describes a risk study of the Browns Ferry, Unit 1, nuclear plant. The study is one of four such studies sponsored by the NRC Office of Research, Division of Risk Assessment, as part of its Interim Reliability Evaluation Program (IREP), Phase II. This report is contained in four volumes: a main report and three appendixes. Appendix C generally describes the methods used to estimate accident sequence frequency values. Information is presented concerning the approach, example collection, failure data, candidate dominant sequences, uncertainty analysis, and sensitivity analysis.

Have first-time medical school deans been serving longer than we thought? A 50-year analysis.

PubMed

Keyes, Joseph A; Alexander, Hershel; Jarawan, Hani; Mallon, William T; Kirch, Darrell G

2010-12-01

To describe the lengths of service of deans at accredited U.S. MD-granting medical schools from academic years 1959 to 2008 and to determine whether the median length of service of deans changed over time. The authors used the database of the Council of Deans of the Association of American Medical Colleges to seek data, from July 1, 1959 to June 30, 2009, on lengths of service of 842 deans and interim deans at all 125 accredited U.S. MD-granting medical schools existing in 2007. All but 8 schools verified their data, which included the date of the beginning of service, the date of the end of service, and whether the individual served in a permanent or interim capacity. Across five-year cohorts of the first-time deans and interim deans studied, the median length of service was 4.4 years. When the authors excluded individuals who were interim deans exclusively and focused the analysis on the 639 persons who were "permanent" deans, the median length of service was 6.0 years across five-year cohorts. Analysis of one-year cohorts of deans showed similar results (median = 6.1 years), although the medians for six of the seven most recent one-year cohorts ranged from 5.0 to 5.7 years. Through cohort analysis, the median length of service of permanent medical school deans was longer than that found in previous studies, and it has remained relatively stable.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 1: Findings from the PDC Implementation Study.

ERIC Educational Resources Information Center

Smith, Allen G.; And Others

This third year interim report, one of a series of documents on the evaluation of Project Developmental Continuity (PDC), presents findings from three major analyses of program implementation; measurement of the extent each program has implemented the basic PDC Guidelines; a description of patterns of that implementation; and analysis of some…

Comparisons of Cooperative and Non-Cooperative Students: An Analysis of Student Accounting System Data. Interim Report, June, 1981.

ERIC Educational Resources Information Center

Frazier, Don

The major purpose of this study was to identify unique effects of cooperative vocational education. This interim report is of results of the analyses of existing data bases. Comparisons of cooperative and non-cooperative vocational programs are made on the following variables: enrollments by age, sex and race, school status, work status,…

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.

PubMed

Strosberg, Jonathan; El-Haddad, Ghassan; Wolin, Edward; Hendifar, Andrew; Yao, James; Chasen, Beth; Mittra, Erik; Kunz, Pamela L; Kulke, Matthew H; Jacene, Heather; Bushnell, David; O'Dorisio, Thomas M; Baum, Richard P; Kulkarni, Harshad R; Caplin, Martyn; Lebtahi, Rachida; Hobday, Timothy; Delpassand, Ebrahim; Van Cutsem, Eric; Benson, Al; Srirajaskanthan, Rajaventhan; Pavel, Marianne; Mora, Jaime; Berlin, Jordan; Grande, Enrique; Reed, Nicholas; Seregni, Ettore; Öberg, Kjell; Lopera Sierra, Maribel; Santoro, Paola; Thevenet, Thomas; Erion, Jack L; Ruszniewski, Philippe; Kwekkeboom, Dik; Krenning, Eric

2017-01-12

Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ( 177 Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177 Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ( 177 Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177 Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177 Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177 Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177 Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Treatment with 177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177 Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

Effectiveness and Tolerability of THC/CBD Oromucosal Spray for Multiple Sclerosis Spasticity in Italy: First Data from a Large Observational Study.

PubMed

Trojano, Maria; Vila, Carlos

2015-01-01

The prospective, non-interventional Mobility Improvement (MOVE) 2 study was designed to provide real life data on clinical outcomes of patients with treatment-resistant multiple sclerosis (MS) spasticity receiving routine treatment with tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®), subsequent to its approval in European countries. This interim analysis reports on MOVE 2 patients from Italy. Interim data from 322 patients (58.3% female; mean age 51.1 ± 10.2 years) were analyzed. From baseline to month 3 of treatment (Visit 3), the mean 0-10 Numerical Rating Scale (NRS) score decreased by -19.1% (-1.6 points, p < 0.0001) and the mean modified Ashworth score decreased from 2.6 to 2.3 points (p < 0.0001). At Visit 3, 24.6% of 203 patients with available data were clinically relevant responders (≥30% improvement from baseline NRS score; p < 0.001 vs. baseline). The mean reported dose of THC:CBD oromucosal spray was 6.1 ± 2.5 sprays/day at Visit 1 (1 month) and 5.1 ± 2.6 sprays/day at Visit 3 (range 1-12 sprays/day at both timepoints). Forty-one (13.1%) patients reported at least one adverse event (AE), which included 3 serious AEs (1 unrelated). AEs with an incidence ≥1% were dizziness (5.6%), confusion (2.5%), nausea (1.25%) and somnolence (1.25%). In everyday clinical practice in Italy, THC:CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant patients. © 2015 S. Karger AG, Basel.

EVALUATION OF THE EFFECTIVENESS OF COATINGS IN REDUCING DISLODGEABLE ARSENIC, CHROMIUM, AND COPPER FROM CCA TREATED WOOD, INTERIM DATA REPORT

EPA Science Inventory

EPA is approximately 20 months into a project to evaluate the performance of wood coatings as a way to prevent arsenic, chromium and copper exposure from the surfaces of CCA treated wood. Potential dermal exposure, as measured by wipe sampling dislodgeable CCA chemical from wood ...

17 CFR 210.3-03 - Instructions to income statement requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... include statements of income and cash flows (which may be unaudited) for the twelve-month period ending on the date of the most recent balance sheet being filed, in lieu of the statements of income and cash flows for the interim periods specified. (c) If a period or periods reported on include operations of a...

17 CFR 210.3-03 - Instructions to income statement requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... include statements of income and cash flows (which may be unaudited) for the twelve-month period ending on the date of the most recent balance sheet being filed, in lieu of the statements of income and cash flows for the interim periods specified. (c) If a period or periods reported on include operations of a...

17 CFR 210.3-03 - Instructions to income statement requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... include statements of income and cash flows (which may be unaudited) for the twelve-month period ending on the date of the most recent balance sheet being filed, in lieu of the statements of income and cash flows for the interim periods specified. (c) If a period or periods reported on include operations of a...

Interim Feasibility Report and Environmental Impact Statement for Oliver Lock Replacement (BWT) Black Warrior-Tombigbee Rivers, Alabama. Revised.

DTIC Science & Technology

1983-12-01

low flow conditions experienced daring summer months in the river above Oliver Lock and Dam (U.S. Army 1981) contribute to depresed water quality and...hence, depresed aquatic resources. These low flow conditions can concentrate pollutants being discharged into the river, resulting in not only toxic

Extended-Day Kindergarten versus Half-Day Kindergarten: What One School District Decided.

ERIC Educational Resources Information Center

Firlik, Russell

The New Canaan Public Schools reduced its extended-day (21 hours per week) kindergarten program to half-day sessions (15 hours per week) in an interim program during a 2-year school construction-expansion phase. During a 9-month planning process, an ad hoc committee representing equal membership of teachers and parents from three elementary…

Educational Information System for Ontario. Second Interim Report, March 1976-February 1977.

ERIC Educational Resources Information Center

Auster, Ethel; Lawton, Stephen B.

This report of the EISO project, the responsibility of which is the operation of an online bibliographic search service for educators of Ontario, concentrates on research findings collected after EISO had been operational for 16 months. The organization, role, and level of satisfaction of EISO users are treated, the system's impact on a school…

Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint.

PubMed

Tang, Zhongwen

2015-01-01

An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

Predictive probability methods for interim monitoring in clinical trials with longitudinal outcomes.

PubMed

Zhou, Ming; Tang, Qi; Lang, Lixin; Xing, Jun; Tatsuoka, Kay

2018-04-17

In clinical research and development, interim monitoring is critical for better decision-making and minimizing the risk of exposing patients to possible ineffective therapies. For interim futility or efficacy monitoring, predictive probability methods are widely adopted in practice. Those methods have been well studied for univariate variables. However, for longitudinal studies, predictive probability methods using univariate information from only completers may not be most efficient, and data from on-going subjects can be utilized to improve efficiency. On the other hand, leveraging information from on-going subjects could allow an interim analysis to be potentially conducted once a sufficient number of subjects reach an earlier time point. For longitudinal outcomes, we derive closed-form formulas for predictive probabilities, including Bayesian predictive probability, predictive power, and conditional power and also give closed-form solutions for predictive probability of success in a future trial and the predictive probability of success of the best dose. When predictive probabilities are used for interim monitoring, we study their distributions and discuss their analytical cutoff values or stopping boundaries that have desired operating characteristics. We show that predictive probabilities utilizing all longitudinal information are more efficient for interim monitoring than that using information from completers only. To illustrate their practical application for longitudinal data, we analyze 2 real data examples from clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 3: Assessment of Program Impact Through the Head Start Year.

ERIC Educational Resources Information Center

Granville, Arthur C.; And Others

This interim report, part of a series of documents examining the feasibility of the longitudinal evaluation of Project Developmental Continuity (PDC), presents the results of an analysis of PDC impact at the Head Start level, using Spring 1977 data. PDC is a Head Start Demonstration Program aimed at providing educational and developmental…

Effectiveness Monitoring Report, MWMF Tritium Phytoremediation Interim Measures.

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

Hitchcock, Dan; Blake, John, I.

2003-02-10

This report describes and presents the results of monitoring activities during irrigation operations for the calendar year 2001 of the MWMF Interim Measures Tritium Phytoremediation Project. The purpose of this effectiveness monitoring report is to provide the information on instrument performance, analysis of CY2001 measurements, and critical relationships needed to manage irrigation operations, estimate efficiency and validate the water and tritium balance model.

Associating extreme precipitation events to parent cyclones in gridded data

NASA Astrophysics Data System (ADS)

Rhodes, Ruari; Shaffrey, Len; Gray, Sue

2015-04-01

When analysing the relationship of regional precipitation to its parent cyclone, it is insufficient to consider the cyclone's region of influence as a fixed radius from the centre due to the irregular shape of rain bands. A new method is therefore presented which allows the use of objective feature tracking data in the analysis of regional precipitation. Utilising the spatial extent of precipitation in gridded datasets, the most appropriate cyclone(s) may be associated with regional precipitation events. This method is applied in the context of an analysis of the influence of clustering and stalling of extra-tropical cyclones in the North Atlantic on total precipitation accumulations over England and Wales. Cyclone counts and residence times are presented for historical records (ERA-Interim) and future projections (HadGEM2-ES) of extreme (> 98th percentile) precipitation accumulations over England and Wales, for accumulation periods ranging from one day to one month.

Activities and interim outcomes of a multi-site development project to promote cognitive support technology use and employment success among postsecondary students with traumatic brain injuries.

PubMed

Hendricks, Deborah J; Sampson, Elaine; Rumrill, Phillip; Leopold, Anne; Elias, Eileen; Jacobs, Karen; Nardone, Amanda; Scherer, Marcia; Stauffer, Callista

2015-01-01

This article describes the activities and interim outcomes of a multi-site development project called Project Career, designed to promote cognitive support technology (CST) use and employment success for college and university students with traumatic brain injuries (TBIs). To obtain early intervention results from participants in Project Career's first 18 months of operation. Fifty-six students with TBI have participated to date across three implementation sites in Massachusetts, Ohio, and West Virginia, with 25 of these participants being military veterans. Descriptive analyses provide information regarding the participants, the barriers they face due to their TBI in obtaining a post-secondary education, and the impact services provided by Project Career have had to date in ameliorating those difficulties. Inferential statistical analyses provide preliminary results regarding program effectiveness. Preliminary results indicate the program is encouraging students to use CST strategies in the form of iPads and cognitive enhancement applications (also known as 'apps'). Significant results indicate participants are more positive, independent, and social; participants have a more positive attitude toward technology after six months in the program; and participants reported significantly improved experiences with technology during their first six months in the program. Participating students are actively preparing for their careers after graduation through a wide range of intensive vocational supports provided by project staff members.

Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)

PubMed Central

Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.

2012-01-01

Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

PubMed

McGarry, Andrew; McDermott, Michael; Kieburtz, Karl; de Blieck, Elisabeth A; Beal, Flint; Marder, Karen; Ross, Christopher; Shoulson, Ira; Gilbert, Peter; Mallonee, William M; Guttman, Mark; Wojcieszek, Joanne; Kumar, Rajeev; LeDoux, Mark S; Jenkins, Mary; Rosas, H Diana; Nance, Martha; Biglan, Kevin; Como, Peter; Dubinsky, Richard M; Shannon, Kathleen M; O'Suilleabhain, Padraig; Chou, Kelvin; Walker, Francis; Martin, Wayne; Wheelock, Vicki L; McCusker, Elizabeth; Jankovic, Joseph; Singer, Carlos; Sanchez-Ramos, Juan; Scott, Burton; Suchowersky, Oksana; Factor, Stewart A; Higgins, Donald S; Molho, Eric; Revilla, Fredy; Caviness, John N; Friedman, Joseph H; Perlmutter, Joel S; Feigin, Andrew; Anderson, Karen; Rodriguez, Ramon; McFarland, Nikolaus R; Margolis, Russell L; Farbman, Eric S; Raymond, Lynn A; Suski, Valerie; Kostyk, Sandra; Colcher, Amy; Seeberger, Lauren; Epping, Eric; Esmail, Sherali; Diaz, Nancy; Fung, Wai Lun Alan; Diamond, Alan; Frank, Samuel; Hanna, Philip; Hermanowicz, Neal; Dure, Leon S; Cudkowicz, Merit

2017-01-10

To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. These data do not justify use of CoQ as a treatment to slow functional decline in HD. NCT00608881. This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD. © 2016 American Academy of Neurology.

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

PubMed

Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

2017-11-01

To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

A prospective trial for laparoscopic adjustable gastric banding in morbidly obese adolescents: an interim report of weight loss, metabolic and quality of life outcomes.

USDA-ARS?s Scientific Manuscript database

The outcome of patients completing 12 months of follow-up in a prospective longitudinal trial of the safety/efficacy of laparoscopic adjustable gastric banding (LAGB), for morbidly obese adolescents aged 14 to 17 years using a Food and Drug Administration Institutional Device Exemption for the use o...

Arsenic Removal from Drinking Water by Adsorptive Media U.S. EPA Demonstration Project at Upper Bodfish in Lake Isabella, CA Interim Evaluation Report

EPA Science Inventory

This report documents the activities performed during and the results obtained from the first 10 months of system operation of an arsenic (As) and uranium (U) removal technology being demonstrated at Upper Bodfish in Lake Isabella, CA. The objectives of the project are to evalua...

Identity Work among Street-Involved Young Mothers

ERIC Educational Resources Information Center

King, Katharine E.; Ross, Lori E.; Bruno, Tara L.; Erickson, Patricia G.

2009-01-01

The Youth Pathways Project tracked the life-course trajectories of street-involved young women (n=75) in Toronto over a one-year period. At first contact, 60% of these women had been pregnant, and 29% of those had children. In the interim leading up to the final interview 12 months later, five participants became pregnant and five had given birth.…

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

PubMed

Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

2017-10-01

The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim analysis. Efficacy assessments were done in all randomly assigned patients (the intention-to-treat population) and the safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01568866, and is no longer enrolling patients. Between June 20, 2012, and June 30, 2014, 1096 patients were assessed for eligibility, of whom 929 were randomly assigned (464 to the carfilzomib group and 465 to the bortezomib group). The cutoff date for this prespecified interim analysis was Jan 3, 2017. Median overall survival was 47·6 months (95% CI 42·5-not evaluable) in the carfilzomib group versus 40·0 months (32·6-42·3) in the bortezomib group (hazard ratio 0·791 [95% CI 0·648-0·964], one-sided p=0·010). Grade 3 or worse adverse events were reported in 377 (81%) of 463 patients in the carfilzomib group and 324 (71%) of 456 patients in the bortezomib group, and serious adverse events in 273 (59%) patients in the carfilzomib group and 182 (40%) in the bortezomib group. The most frequent grade 3 or worse adverse events were anaemia (76 [16%] of 463 patients in the carfilzomib group vs 46 [10%] of 456 patients in the bortezomib group), hypertension (67 [15%] vs 15 [3%]), pneumonia (42 [9%] vs 39 [9%]), thrombocytopenia (41 [9%] vs 43 [9%]), fatigue (31 [7%] vs 35 [8%]), dyspnoea (29 [6%] vs ten [2%]), decreased lymphocyte count (29 [6%] vs nine [2%]), diarrhoea (18 [4%] vs 39 [9%]), and peripheral neuropathy (six [1%] vs 28 [6%]). Treatment-related deaths occurred in five (1%) of 463 patients in the carfilzomib group (pneumonia [n=2], interstitial lung disease [n=1], septic shock [n=1], and unknown [n=1]) and two (<1%) of 456 patients in the bortezomib group (cardiac arrest [n=1] and pneumonia [n=1]). Carfilzomib provided a significant and clinically meaningful reduction in the risk of death compared with bortezomib. To our knowledge, carfilzomib is the first and only multiple myeloma treatment that extends overall survival in the relapsed setting over the current standard of care. This study is informative for deciding which proteasome inhibitor to use for treating this disease. Onyx Pharmaceuticals Inc, an Amgen Inc subsidiary. Copyright © 2017 Elsevier Ltd. All rights reserved.

THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

PubMed

Trojano, Maria

2016-01-01

The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013. Web-based real-time data collection techniques are combined with traditional patients' diaries to capture a wide spectrum of outcomes associated with this innovative cannabis-based medication. After surpassing the recruitment threshold of 300 patients, an interim analysis was performed to determine whether the data collected to date align with those from MOVE 2-Germany and the largest phase III randomized controlled trial (RCT) of THC:CBD oromucosal spray. In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months' observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT. While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity. © 2016 S. Karger AG, Basel.

Functions and requirements document for interim store solidified high-level and transuranic waste

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

Smith-Fewell, M.A., Westinghouse Hanford

1996-05-17

The functions, requirements, interfaces, and architectures contained within the Functions and Requirements (F{ampersand}R) Document are based on the information currently contained within the TWRS Functions and Requirements database. The database also documents the set of technically defensible functions and requirements associated with the solidified waste interim storage mission.The F{ampersand}R Document provides a snapshot in time of the technical baseline for the project. The F{ampersand}R document is the product of functional analysis, requirements allocation and architectural structure definition. The technical baseline described in this document is traceable to the TWRS function 4.2.4.1, Interim Store Solidified Waste, and its related requirements, architecture,more » and interfaces.« less

A Procedure for Structural Weight Estimation of Single Stage to Orbit Launch Vehicles (Interim User's Manual)

NASA Technical Reports Server (NTRS)

Martinovic, Zoran N.; Cerro, Jeffrey A.

2002-01-01

This is an interim user's manual for current procedures used in the Vehicle Analysis Branch at NASA Langley Research Center, Hampton, Virginia, for launch vehicle structural subsystem weight estimation based on finite element modeling and structural analysis. The process is intended to complement traditional methods of conceptual and early preliminary structural design such as the application of empirical weight estimation or application of classical engineering design equations and criteria on one dimensional "line" models. Functions of two commercially available software codes are coupled together. Vehicle modeling and analysis are done using SDRC/I-DEAS, and structural sizing is performed with the Collier Research Corp. HyperSizer program.

Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial.

PubMed

Saussele, Susanne; Richter, Johan; Guilhot, Joelle; Gruber, Franz X; Hjorth-Hansen, Henrik; Almeida, Antonio; Janssen, Jeroen J W M; Mayer, Jiri; Koskenvesa, Perttu; Panayiotidis, Panayiotis; Olsson-Strömberg, Ulla; Martinez-Lopez, Joaquin; Rousselot, Philippe; Vestergaard, Hanne; Ehrencrona, Hans; Kairisto, Veli; Machová Poláková, Katerina; Müller, Martin C; Mustjoki, Satu; Berger, Marc G; Fabarius, Alice; Hofmann, Wolf-Karsten; Hochhaus, Andreas; Pfirrmann, Markus; Mahon, Francois-Xavier

2018-06-01

Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year. The primary endpoint was molecular relapse-free survival, defined by loss of major molecular response (MMR; >0·1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result. Secondary endpoints were a prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy. We considered loss of haematological response, progress to accelerated-phase chronic myeloid leukaemia, or blast crisis as serious adverse events. This study presents the results of the prespecified interim analysis, which was done after the 6-month molecular relapse-free survival status was known for 200 patients. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01596114. Between May 30, 2012, and Dec 3, 2014, we assessed 868 patients with chronic myeloid leukaemia for eligibility, of whom 758 were enrolled. Median follow-up of the 755 patients evaluable for molecular response was 27 months (IQR 21-34). Molecular relapse-free survival for these patients was 61% (95% CI 57-64) at 6 months and 50% (46-54) at 24 months. Of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR. A further six (1%) patients died in chronic-phase chronic myeloid leukaemia after loss of MMR and re-initiation of TKI therapy for reasons unrelated to chronic myeloid leukaemia, and two (<1%) patients lost MMR despite restarting TKI therapy. In the prognostic analysis in 405 patients who received imatinib as first-line treatment (learning sample), longer treatment duration (odds ratio [OR] per year 1·14 [95% CI 1·05-1·23]; p=0·0010) and longer deep molecular response durations (1·13 [1·04-1·23]; p=0·0032) were associated with increasing probability of MMR maintenance at 6 months. The OR for deep molecular response duration was replicated in the validation sample consisting of 171 patients treated with any TKI as first-line treatment, although the association was not significant (1·13 [0·98-1·29]; p=0·08). TKI discontinuation was associated with substantial cost savings (an estimated €22 million). No serious adverse events were reported. Patients with chronic myeloid leukaemia who have achieved deep molecular responses have good molecular relapse-free survival. Such patients should be considered for TKI discontinuation, particularly those who have been in deep molecular response for a long time. Stopping treatment could spare patients from treatment-induced side-effects and reduce health expenditure. ELN Foundation and France National Cancer Institute. Copyright © 2018 Elsevier Ltd. All rights reserved.

An intercomparison of stratospheric gravity wave potential energy densities from METOP GPS radio occultation measurements and ECMWF model data

NASA Astrophysics Data System (ADS)

Rapp, Markus; Dörnbrack, Andreas; Kaifler, Bernd

2018-02-01

Temperature profiles based on radio occultation (RO) measurements with the operational European METOP satellites are used to derive monthly mean global distributions of stratospheric (20-40 km) gravity wave (GW) potential energy densities (EP) for the period July 2014-December 2016. In order to test whether the sampling and data quality of this data set is sufficient for scientific analysis, we investigate to what degree the METOP observations agree quantitatively with ECMWF operational analysis (IFS data) and reanalysis (ERA-Interim) data. A systematic comparison between corresponding monthly mean temperature fields determined for a latitude-longitude-altitude grid of 5° by 10° by 1 km is carried out. This yields very low systematic differences between RO and model data below 30 km (i.e., median temperature differences is between -0.2 and +0.3 K), which increases with height to yield median differences of +1.0 K at 34 km and +2.2 K at 40 km. Comparing EP values for three selected locations at which also ground-based lidar measurements are available yields excellent agreement between RO and IFS data below 35 km. ERA-Interim underestimates EP under conditions of strong local mountain wave forcing over northern Scandinavia which is apparently not resolved by the model. Above 35 km, RO values are consistently much larger than model values, which is likely caused by the model sponge layer, which damps small-scale fluctuations above ˜ 32 km altitude. Another reason is the well-known significant increase of noise in RO measurements above 35 km. The comparison between RO and lidar data reveals very good qualitative agreement in terms of the seasonal variation of EP, but RO values are consistently smaller than lidar values by about a factor of 2. This discrepancy is likely caused by the very different sampling characteristics of RO and lidar observations. Direct comparison of the global data set of RO and model EP fields shows large correlation coefficients (0.4-1.0) with a general degradation with increasing altitude. Concerning absolute differences between observed and modeled EP values, the median difference is relatively small at all altitudes (but increasing with altitude) with an exception between 20 and 25 km, where the median difference between RO and model data is increased and the corresponding variability is also found to be very large. The reason for this is identified as an artifact of the EP algorithm: this erroneously interprets the pronounced climatological feature of the tropical tropopause inversion layer (TTIL) as GW activity, hence yielding very large EP values in this area and also large differences between model and observations. This is because the RO data show a more pronounced TTIL than IFS and ERA-Interim. We suggest a correction for this effect based on an estimate of this artificial EP using monthly mean zonal mean temperature profiles. This correction may be recommended for application to data sets that can only be analyzed using a vertical background determination method such as the METOP data with relatively scarce sampling statistics. However, if the sampling statistics allows, our analysis also shows that in general a horizontal background determination is advantageous in that it better avoids contributions to EP that are not caused by gravity waves.

Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study.

PubMed

Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Tuboi, Suely; Garbes, Pedro; Borkowski, Astrid; Wallace, Derek

2017-06-01

Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4). An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2-17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 10 4 plaque-forming units [PFU] of TDV-1; 6·3 × 10 3 PFU of TDV-2; 3·2 × 10 4 PFU of TDV-3; and 4·0 × 10 5 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1-4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT02302066. 1800 participants were enrolled between Dec 5, 2014, and Feb 13, 2015. 1794 participants were given study injection as follows: 200 participants were given two-dose regimen at 0 and 3 months (group 1), 398 were given one dose at 0 months (group 2), 998 were given one dose at 0 months and will be given (trial ongoing) a booster at 12 months (group 3), and 198 were given placebo (group 4). These 1794 participants were included in the safety set; 562 participants were randomly assigned to the immunogenicity subset, of which 503 were included in the per-protocol set. TDV elicited neutralising antibodies against all DENV serotypes, which peaked at 1 month and remained elevated above baseline at 6 months. At 6 months, GMTs of neutralising antibodies against DENV-1 were 489 (95% CI 321-746) for group 1, 434 (306-615) for group 2, 532 (384-738) for group 3, and 62 (32-120) for group 4; GMTs of neutralising antibodies against DENV-2 were 1565 (1145-2140) for group 1, 1639 (1286-2088) for group 2, 1288 (1031-1610) for group 3, and 86 (44-169) for group 4; GMTs of neutralising antibodies against DENV-3 were 160 (104-248) for group 1, 151 (106-214) for group 2, 173 (124-240) for group 3, and 40 (23-71) for group 4; and GMTs of neutralising antibodies against DENV-4 were 117 (79-175) for group 1, 110 (80-149) for group 2, 93 (69-125) for group 3, and 24 (15-38) for group 4. No vaccine-related serious adverse events occurred; 15 (3%) of 562 participants in the immunogenicity subset reported vaccine-related unsolicited adverse events. The reactogenicity profile of TDV was acceptable, and similar to previous findings with TDV. TDV is safe and immunogenic in individuals aged 2-17 years, irrespective of previous dengue exposure. A second TDV dose induced enhanced immunogenicity against DENV-3 and DENV-4 in children who were seronegative before vaccination. These data supported the initiation of phase 3 evaluation of the efficacy and safety of TDV given in a two-dose schedule 3 months apart, with analyses that take into account baseline age and dengue serostatus. Takeda Vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimal screening and donor management in a public stool bank.

PubMed

Kazerouni, Abbas; Burgess, James; Burns, Laura J; Wein, Lawrence M

2015-12-17

Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.

On the comparisons of tropical relative humidity in the lower and middle troposphere among COSMIC radio occultations, MERRA and ECMWF data sets

NASA Astrophysics Data System (ADS)

Vergados, P.; Mannucci, A. J.; Ao, C. O.; Jiang, J. H.; Su, H.

2015-01-01

The spatial variability of the tropical tropospheric relative humidity (RH) throughout the vertical extent of the troposphere is examined using Global Positioning System Radio Occultation (GPSRO) observations from the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) mission. These high vertical resolution observations capture the detailed structure and moisture budget of the Hadley Cell circulation. We compare the COSMIC observations with the European Center for Medium-range Weather Forecast (ECMWF) Re-Analysis Interim (ERA-Interim) and the Modern-Era Retrospective analysis for Research and Applications (MERRA) climatologies. Qualitatively, the spatial pattern of RH in all data sets matches up remarkably well, capturing distinct features of the general circulation. However, RH discrepancies exist between ERA-Interim and COSMIC data sets, which are noticeable across the tropical boundary layer. Specifically, ERA-Interim shows a drier Inter Tropical Convergence Zone (ITCZ) by 15-20% compared both to COSMIC and MERRA data sets, but this difference decreases with altitude. Unlike ECMWF, MERRA shows an excellent agreement with the COSMIC observations except above 400 hPa, where GPSRO observations capture drier air by 5-10%. RH climatologies were also used to evaluate intraseasonal variability. The results indicate that the tropical middle troposphere at ±5-25° is most sensitive to seasonal variations. COSMIC and MERRA data sets capture the same magnitude of the seasonal variability, but ERA-Interim shows a weaker seasonal fluctuation up to 10% in the middle troposphere inside the dry air subsidence regions of the Hadley Cell. Over the ITCZ, RH varies by maximum 9% between winter and summer.

Land Surface Precipitation and Hydrology in MERRA-2

NASA Technical Reports Server (NTRS)

Reichle, R.; Koster, R.; Draper, C.; Liu, Q.; Girotto, M.; Mahanama, S.; De Lannoy, G.; Partyka, G.

2017-01-01

The Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), provides global, 1-hourly estimates of land surface conditions for 1980-present at 50-km resolution. Outside of the high latitudes, MERRA-2 uses observations-based precipitation data products to correct the precipitation falling on the land surface. This paper describes the precipitation correction method and evaluates the MERRA-2 land surface precipitation and hydrology. Compared to monthly GPCPv2.2 observations, the corrected MERRA-2 precipitation (M2CORR) is better than the precipitation generated by the atmospheric models within the cyclingMERRA-2 system and the earlier MERRA reanalysis. Compared to 3-hourlyTRMM observations, the M2CORR diurnal cycle has better amplitude but less realistic phasing than MERRA-2 model-generated precipitation. Because correcting the precipitation within the coupled atmosphere-land modeling system allows the MERRA-2 near-surface air temperature and humidity to respond to the improved precipitation forcing, MERRA-2 provides more self-consistent surface meteorological data than were available from the earlier, offline MERRA-Land reanalysis. Overall, MERRA-2 land hydrology estimates are better than those of MERRA-Land and MERRA. A comparison against GRACE satellite observations of terrestrial water storage demonstrates clear improvements in MERRA-2 over MERRA in South America and Africa but also reflects known errors in the observations used to correct the MERRA-2 precipitation. The MERRA-2 and MERRA-Land surface and root zone soil moisture skill vs. in situ measurements is slightly higher than that of ERA-Interim Land and higher than that of MERRA (significantly for surface soil moisture). Snow amounts from MERRA-2 have lower bias and correlate better against reference data than do those of MERRA-Land and MERRA, with MERRA-2 skill roughly matching that of ERA-Interim Land. Seasonal anomaly R values against naturalized stream flow measurements in the United States are, on balance, highest for MERRA-2 and ERA-Interim Land, somewhat lower for MERRA-Land, and lower still for MERRA.

Assessing variability of evapotranspiration over the Ganga river basin using water balance computations

NASA Astrophysics Data System (ADS)

Syed, Tajdarul H.; Webster, Peter J.; Famiglietti, James S.

2014-03-01

A thorough assessment of evapotranspiration (ET) pervades several important issues of the 21st century including climate change, food-security, land-management, flood and drought prediction, and water resources assessment and management. Such a proper assessment is of particular importance in the Ganga river basin (GRB) with its backdrop of a rapidly increasing population pressure and unregulated use of water resources. Spatially averaged ET over the GRB is computed as the residual of atmospheric and terrestrial water budget computations using a combination of model simulations and satellite and ground-based observations. The best estimate of monthly ET is obtained as the monthly mean of atmospheric and terrestrial water balance computations for the period 1980-2007. The mean monthly average of ET from these various estimates is 72.3 ± 18.8 mm month-1. Monthly variations of ET peak between July and August and reach a minimum in February. For the entire study period, the rate of change of ET across the GRB is -11 mm yr-2 (i.e., mm/yr/yr). Alongside a notable influence of the 1997-1998 El Niño, results allude to the existence of interim periods during which ET trends varied significantly. More specifically, during the period of 1998-2002, the rate of decline increased to -55.8 mm yr-2, which is almost 5 times the overall trend. Based on the correlation between ET and independent estimates of near-surface temperature and soil moisture, we can infer that the ET over the GRB is primarily limited by moisture availability. The analysis has important potential for use in large-scale water budget assessments and intercomparison studies. The analysis also emphasizes the importance of synergistic use of mutliplatform hydrologic information.

The Family and Medical Leave Act of 1993--Wage and Hour Division, Department of Labor. Interim final rule; request for comments.

PubMed

1993-06-04

This document contains interim regulations implementing the Family and Medical Leave Act of 1993 called ("FMLA" or "the Act"). The Act is effective on August 5, 1993, six months from the date of its enactment. Where a collective bargaining agreement is in effect on August 5, 1993, the Act is effective when the collective bargaining agreement terminates or February 5, 1994, whichever is earlier. The purpose of these regulations is to set forth the requirements of Title I and Title IV of the Act. Title I applies to covered private employers and public agencies (except for most of the Federal Government, which is governed by Title II). Title IV of the Act primarily concerns the relationship between FMLA and other laws, as well as collective bargaining agreements and other employer plans and programs.

Interim Air Purity Guidelines for Dry Deck Shelter (DDS) Operations

DTIC Science & Technology

1990-10-01

The acceptable limits for gaseous contaminants in submarine compressed air for use as diver’s breathing air are derived from the 8-hour Time Weighted...accompanying documentation. Cylinders must be declared as hazardous cargo (" Air , Compressed Non-Flammable Gas") prior to air transport. Analysis of cylinder...capi NAVAL MEDICAL RESEARCH INSTITUTE Bethesda, MD 20889-5055 NMRI 90-109 October 1990 AD-A231 432 INTERIM AIR PURITY GUIDELINES FOR DRY DECK

Terrestrial gravity data analysis for interim gravity model improvement

NASA Technical Reports Server (NTRS)

1987-01-01

This is the first status report for the Interim Gravity Model research effort that was started on June 30, 1986. The basic theme of this study is to develop appropriate models and adjustment procedures for estimating potential coefficients from terrestrial gravity data. The plan is to use the latest gravity data sets to produce coefficient estimates as well as to provide normal equations to NASA for use in the TOPEX/POSEIDON gravity field modeling program.

National NIF Diagnostic Program Fiscal Year 2002 Second Quarter Report

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

MacGowan, B

Since October 2001 the development of the facility diagnostics for NIF has been funded by the NIF Director through the National NIF Diagnostic Program (NNDP). The current emphasis of the NNDP is on diagnostics for the early NIF quad scheduled to be available for experiment commissioning in FY03. During the past six months the NNDP has set in place processes for funding diagnostics, developing requirements for diagnostics, design reviews and monthly status reporting. Those processes are described in an interim management plan for diagnostics (''National NIF Diagnostic Program Interim Plan'', NIF-0081315, April 2002) and a draft Program Execution Plan (''Programmore » Execution Plan for the National NlF Diagnostic Program'', NIF-0072083, October 2001) and documents cited therein. Work has been funded at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Naval Research Laboratory (NRL), Sandia National Laboratories (SNL), Bechtel Nevada at Los Alamos and Santa Barbara. There are no major technical risks with the early diagnostics. The main concerns relate to integration of the diagnostics into the facility, all such issues are being worked. This report is organized to show the schedule and budget status and a summary of Change Control Board actions for the past six months. The following sections then provide short descriptions of the status of each diagnostic. Where design reviews or requirements documents are cited, the documents are available on the Diagnostics file server or on request.« less

Maximum inflation of the type 1 error rate when sample size and allocation rate are adapted in a pre-planned interim look.

PubMed

Graf, Alexandra C; Bauer, Peter

2011-06-30

We calculate the maximum type 1 error rate of the pre-planned conventional fixed sample size test for comparing the means of independent normal distributions (with common known variance) which can be yielded when sample size and allocation rate to the treatment arms can be modified in an interim analysis. Thereby it is assumed that the experimenter fully exploits knowledge of the unblinded interim estimates of the treatment effects in order to maximize the conditional type 1 error rate. The 'worst-case' strategies require knowledge of the unknown common treatment effect under the null hypothesis. Although this is a rather hypothetical scenario it may be approached in practice when using a standard control treatment for which precise estimates are available from historical data. The maximum inflation of the type 1 error rate is substantially larger than derived by Proschan and Hunsberger (Biometrics 1995; 51:1315-1324) for design modifications applying balanced samples before and after the interim analysis. Corresponding upper limits for the maximum type 1 error rate are calculated for a number of situations arising from practical considerations (e.g. restricting the maximum sample size, not allowing sample size to decrease, allowing only increase in the sample size in the experimental treatment). The application is discussed for a motivating example. Copyright © 2011 John Wiley & Sons, Ltd.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

PubMed

Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

2016-05-03

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

PubMed

Eichler, Florian; Duncan, Christine; Musolino, Patricia L; Orchard, Paul J; De Oliveira, Satiro; Thrasher, Adrian J; Armant, Myriam; Dansereau, Colleen; Lund, Troy C; Miller, Weston P; Raymond, Gerald V; Sankar, Raman; Shah, Ami J; Sevin, Caroline; Gaspar, H Bobby; Gissen, Paul; Amartino, Hernan; Bratkovic, Drago; Smith, Nicholas J C; Paker, Asif M; Shamir, Esther; O'Meara, Tara; Davidson, David; Aubourg, Patrick; Williams, David A

2017-10-26

In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM ClinicalTrials.gov number, NCT01896102 ; ClinicalTrialsRegister.eu number, 2011-001953-10 .).

A new methodology for assessment of pectus excavatum correction after bar removal in Nuss procedure: Preliminary study.

PubMed

Gomes-Fonseca, João; Vilaça, João L; Henriques-Coelho, Tiago; Direito-Santos, Bruno; Pinho, António C M; Fonseca, Jaime C; Correia-Pinto, Jorge

2017-07-01

The objective is to present a new methodology to assess quantitatively the impact of bar removal on the anterior chest wall, among patients with pectus excavatum who have undergone the Nuss procedure, and present a preliminary study using this methodology. We propose to acquire, for each patient, the surface of the anterior chest wall using a three-dimensional laser scanner at subsequent time points (short term: before and after surgery; long term: follow-up visit, 6months, and 12months after surgery). After surfaces postprocessing, the changes are assessed by overlapping and measuring the distances between surfaces. In this preliminary study, three time points were acquired and two assessments were performed: before vs after bar removal (early) and before vs 2-8weeks after bar removal (interim). In 21 patients, the signed distances and volumes between surfaces were computed and the data analysis was performed. This methodology revealed useful for monitoring changes in the anterior chest wall. On average, the mean, maximum, and volume variations, in the early assessment, were -0.1±0.1cm, -0.6±0.2cm, and 47.8±22.2cm 3 , respectively; and, in the interim assessment, were -0.5±0.2cm, -1.3±0.4cm, and 122.1±47.3cm 3 , respectively (p<0.05). Data analysis revealed that the time the bar was in situ was inversely and significantly correlated with postretraction and was a relevant predictor of its decrease following surgery (p<0.05). Additionally, gender and age suggested influencing the outcome. This methodology is novel, objective and safe, helping on follow-up of pectus excavatum patients. Moreover, the preliminary study suggests that the time the bar was in situ may be the main determinant of the anterior chest wall retraction following bar removal. Further studies should continue to corroborate and reinforce the preliminary findings, by increasing the sample size and performing long-term assessments. III. Copyright © 2017 Elsevier Inc. All rights reserved.

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

PubMed

Ning, Yang-Min; Brave, Michael; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard

2015-08-01

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14-0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30-0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. ©AlphaMed Press.

Relationship of Eating Patterns and Metabolic Parameters, and Teneligliptin Treatment: Interim Results from Post-marketing Surveillance in Japanese Type 2 Diabetes Patients.

PubMed

Kadowaki, Takashi; Haneda, Masakazu; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Matsukawa, Miyuki; Ueno, Makoto

2018-06-01

Healthy eating is a critical aspect of the prevention and management of type 2 diabetes (T2DM). Disrupted eating patterns can result in poor glucose control and increase the likelihood of diabetic complications. Teneligliptin inhibits dipeptidyl peptidase-4 activity for 24 h and suppresses postprandial hyperglycemia after all three daily meals. This interim analysis of data from the large-scale post-marketing surveillance of teneligliptin (RUBY) in Japan examined eating patterns and their relationship with metabolic parameters and diabetic complications. We also examined whether eating patterns affected safety and efficacy of teneligliptin. We analyzed baseline data from survey forms collected in RUBY between May 2013 and June 2017, including patient characteristics, metabolic parameters, and eating patterns (eating three meals per day or not; timing of evening meal) before teneligliptin treatment was initiated. Safety and efficacy of 12 months' teneligliptin (20-40 mg/day) treatment was assessed. Data from 10,532 patients were available for analysis. Most patients who did not eat three meals per day (n  =757) or who ate their evening meal after 10 PM (n  =206) were 64 years old or younger. At baseline, glycated hemoglobin (HbA1c), fasting blood glucose, triglycerides, total and low-density lipoprotein cholesterol, body mass index, alanine aminotransferase, and aspartate aminotransferase levels were higher in those patients who did not eat three meals per day (p < 0.05) or who ate their evening meal late (p < 0.05). Diabetic complications were more common in patients who did not eat three meals per day. Treatment with teneligliptin reduced HbA1c over 6 or 12 months across all eating patterns, with a low incidence of adverse drug reactions. Eating patterns may be associated with altered metabolic parameters and diabetic complications among Japanese patients with T2DM. Teneligliptin may be well tolerated and improve hyperglycemia in patients with T2DM irrespective of eating patterns. Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co. Ltd. Japic CTI-153047.

TOSCA - first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex.

PubMed

Kingswood, John C; Bruzzi, Paolo; Curatolo, Paolo; de Vries, Petrus J; Fladrowski, Carla; Hertzberg, Christoph; Jansen, Anna C; Jozwiak, Sergiusz; Nabbout, Rima; Sauter, Matthias; Touraine, Renaud; O'Callaghan, Finbar; Zonnenberg, Bernard; Crippa, Stefania; Comis, Silvia; d'Augères, Guillaume Beaure; Belousova, Elena; Carter, Tom; Cottin, Vincent; Dahlin, Maria; Ferreira, José Carlos; Macaya, Alfons; Benedik, Mirjana Perkovic; Sander, Valentin; Youroukos, Sotirios; Castellana, Ramon; Ulker, Bulent; Feucht, Martha

2014-11-26

Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies. TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a 'core' section and subsections or 'petals'. The 'core' section is designed to record general information on patients' background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24 months. A follow-up observation period of up to 5 years is planned. A pre-planned administrative analysis of 'core' data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to data availability in 2014. The results of TOSCA will assist in filling the gaps in understanding the natural history of TSC and help in planning better management and surveillance strategies. This large-scale international registry to study TSC could serve as a model to encourage planning of similar registries for other rare diseases.

Comparative risk assessments for the production and interim storage of glass and ceramic waste forms: Defense waste processing facility

NASA Astrophysics Data System (ADS)

Huang, J. C.; Wright, W. V.

1982-04-01

The Defense Waste Processing Facility (DWPF) for immobilizing nuclear high level waste (HLW) is scheduled to be built. High level waste is produced when reactor components are subjected to chemical separation operations. Two candidates for immobilizing this HLW are borosilicate glass and crystalline ceramic, either being contained in weld sealed stainless steel canisters. A number of technical analyses are being conducted to support a selection between these two waste forms. The risks associated with the manufacture and interim storage of these two forms in the DWPF are compared. Process information used in the risk analysis was taken primarily from a DWPF processibility analysis. The DWPF environmental analysis provided much of the necessary environmental information.

Interim reliability-evaluation program: analysis of the Browns Ferry, Unit 1, nuclear plant. Appendix B - system descriptions and fault trees

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

Mays, S.E.; Poloski, J.P.; Sullivan, W.H.

1982-07-01

This report describes a risk study of the Browns Ferry, Unit 1, nuclear plant. The study is one of four such studies sponsored by the NRC Office of Research, Division of Risk Assessment, as part of its Interim Reliability Evaluation Program (IREP), Phase II. This report is contained in four volumes: a main report and three appendixes. Appendix B provides a description of Browns Ferry, Unit 1, plant systems and the failure evaluation of those systems as they apply to accidents at Browns Ferry. Information is presented concerning front-line system fault analysis; support system fault analysis; human error models andmore » probabilities; and generic control circuit analyses.« less

How well do Reanalysis represent polar lows?

NASA Astrophysics Data System (ADS)

Zappa, G.; Shaffrey, L.; Hodges, K.

2013-12-01

Polar lows are intense maritime mesocyclones forming at high latitudes during polar air outbreaks. The associated high surface winds can be an important cause of coastal damage.They also seem to play a relevant role in the climate system by modulating the oceanic surface heat fluxes. This creates strong interest in understanding whether modern reanalysis datasets are able to represent polar lows, as well as how their representation may be sensitive to the model resolution. In this talk we investigate how ERA-Interim reanalysis represents the polar lows identified by the Norwegian meteorological services and listed in the STARS (Combination of Sea Surface Temperature and AltimeteR Synergy) dataset for the period 2002-2011. The sensitivity to resolution is explored by comparing ERA-Interim to the ECMWF operational analyses (2008-2011), which have three times higher horizontal resolution compared to ERA-Interim. We show that ERAI-Interim has excellent ability to capture the observed polar lows events with up to 90% of the observed events being found in the reanalysis. However, ERA-Interim tends to have polar lows of weaker dynamical intensity, in terms of both winds and vorticity, and with less spatial structure than in the ECMWF operational analyses (See Fig 1). Furthermore, we apply an objective feature tracking algorithm to the 3 hourly vorticity at 850 hPa with constraints on vorticity intensity and atmospheric static stability to objectively identify polar lows in the ERA-Interim reanalysis. We show that for the stronger polar lows the objective climatology shows good agreement with the STARS dataset over the 2002-2011 period. This allows us to extend the polar lows climatology over the whole ERA Interim period. Differences with another reanalysis product (NCEP-CFSR) will be also discussed. Fig 1: Composite of the tangential wind speed at 925 hPa for 34 polar lows observed in the Norwegian sea between 2008-2010 as represented by the ERA-Interim reanalysis (left) and by the ECMWF Operational analysis (right). Positive values indicate cyclonic circulation. The composite is centered on the polar low vorticity maxima and it is presented for a radial cap of 5 degrees of radius on the sphere (~550Km).

Symptomatic treatment in multiple sclerosis-interim analysis of a nationwide registry.

PubMed

Skierlo, S; Rommer, P S; Zettl, U K

2017-04-01

To analyze symptomatic treatment in patients with multiple sclerosis (MS). Multiple sclerosis is a chronic inflammatory disease of the central nervous system, with accumulating disability symptoms like spasticity, voiding disorders, depression, and pain might occur. The nationwide German MS registry was initiated 2001 under guidance of the German MS society (Deutsche MS Gesellschaft). This study was performed as an interim analysis to lay foundation for future work on this topic. A subcohort of 5113 patients was assessed for this interim analysis. The mean age of the patients was 45.3 years; mean EDSS was 4.2. More than two-third of the enrolled patients were females (70.9%). Most frequent symptoms were fatigue (60%), followed by spasticity (52.5%) and voiding disorders (51.7%). The likelihood of treatment was highest for epileptic disorders (68.8%), spasticity (68.5%), pain (60.7%), and depression (58.9%). Multivariate regression analysis showed that retirement was the strongest factor predictive for antispastic treatment (β=.061, P=.005). Almost all patients in this analysis suffer from symptoms due to advanced MS. Treatment for the various symptoms differed tremendously. The likelihood of treatment correlated with the availability of effective therapeutic agents. Clinicians should put more awareness on MS symptoms. Symptomatic treatment may improve quality of life. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vemurafenib: in unresectable or metastatic melanoma.

PubMed

Keating, Gillian M

2012-10-01

Vemurafenib is a first-in-class, small molecule BRAFV600E inhibitor. It is indicated in the US for the treatment of patients with unresectable or metastatic melanoma with the BRAFV600E mutation, and in the EU as monotherapy in adults with BRAFV600 mutation-positive unresectable or metastatic melanoma. Oral vemurafenib improved overall survival (OS) [co-primary endpoint] in patients with unresectable, previously untreated, BRAFV600E mutation-positive, stage IIIC or IV melanoma, according to the results of a randomized, open-label, multicenter, phase III trial (BRIM-3). With vemurafenib versus dacarbazine, the risk of death was significantly reduced by 63% in the interim OS analysis, and by 56%, 38%, and 30% in subsequent updated OS analyses. The median OS duration was 13.6 months in vemurafenib recipients and 9.7 months in dacarbazine recipients in the most recent OS analysis. In the phase III trial, progression-free survival (PFS) [co-primary endpoint] was also significantly improved in vemurafenib versus dacarbazine recipients (median PFS of 5.3 vs 1.6 months), with a significant reduction in the risk of death or disease progression of 74% in the final PFS analysis. Vemurafenib was also associated with a high overall response rate in patients with previously treated, BRAFV600 mutation-positive, stage IV melanoma, according to the results of a noncomparative, multicenter, phase II trial. Patients had received at least one prior systemic treatment for advanced disease (excluding BRAF inhibitors other than sorafenib or MEK inhibitors). The overall response rate (primary endpoint) was 53% (complete response rate of 6% and partial response rate of 47%), with a median duration of response of 6.7 months, and a median OS duration of 15.9 months. Oral vemurafenib was generally well tolerated in patients with metastatic melanoma, with cutaneous adverse events among the most commonly occurring adverse events. Cutaneous squamous cell carcinoma and/or keratoacanthoma were reported in 18% of vemurafenib recipients in the BRIM-3 trial.

76 FR 4369 - Interim Deputation Agreements; Interim BIA Adult Detention Facility Guidelines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... Adult Detention Facility Guidelines AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice. SUMMARY: This notice announces the online publication of the Interim BIA Adult Detention Facility Guidelines and... Indian Affairs Web site. DATES: These Interim BIA Adult Detention Facility Guidelines and Interim Model...

Frequency and Type of Prosthetic Complications Associated with Interim, Immediately Loaded Full-Arch Prostheses: A 2-Year Retrospective Chart Review.

PubMed

Drago, Carl

2016-08-01

The purpose of this report was to retrospectively evaluate implant and immediate full-arch prosthesis survival rates over a 24-month period; patients were consecutively treated with immediate occlusal loading. Dental arch, gender, and implant orientation (vertical vs. tilted) were also noted. All Brånemark System implants (Nobel Active) and interim, all-acrylic resin prostheses placed in patients following an All-on-Four™ protocol, in a single private practice were assessed by retrospective patient chart review. The amount of space provided surgically for implant restorative components and prostheses was determined from measurements of the vertical heights of the interim prostheses in the right/left anterior and posterior segments. These measurements were made in the laboratory. Interim prosthetic repairs (type, frequency, length of time from insertion) were analyzed by type, arch, gender, and implant orientation. Implant survival and insertion torque values were also measured. Inclusion criteria consisted of all Brånemark System implants placed with the All-on-Four protocol from September 1, 2011, until August 31, 2013. Specific dietary instructions were given for the first 7 days immediately postoperatively and for the weeks prior to insertion of the definitive prostheses. One hundred twenty-nine patients, comprising 191 arches (766 implants) from September 1, 2011, until August 31, 2013, were included in the study. One patient experienced implant failure yielding an overall implant survival rate (SR) of 99.5% (762 of 766). Four hundred twenty-six of 430 maxillary implants and 336 of 336 mandibular implants survived for SRs of 99.1% and 100%, respectively. Regarding implant orientation, 415 of 417 tilted implants (SR 99.5%) and 343 of 345 (CSR 95.6%) vertical implants were noted to be clinically stable. Interim, all-acrylic resin prostheses were in place for a mean of 199.2 days; mandibular prostheses were in place for an average of 195.4 days; maxillary prostheses were in place for an average of 202.0 days. Thirty four of the 191 interim prostheses (17.8%) warranted at least one repair during the treatment period. The average overall implant insertion torque value was 60.74 Ncm; mandibular torque values averaged 63.08 Ncm; maxillary torque values averaged 59.00 Ncm. The results from this study suggest that dental arch, gender, and implant orientation for implants placed and immediately restored with interim, all-acrylic resin, full-arch prostheses per the All-on-Four protocol did not have significant statistical or clinical effects on prosthetic complications of the interim prostheses or implant survival. Only one of the 129 patients experienced implant failures, indicating that the All-on-Four treatment protocol used in this study is a viable alternative to other protocols for rehabilitating edentulous patients. © 2015 by the American College of Prosthodontists.

U.S. Policy Toward the Israeli-Egyptian Conflict September 1970-February 1972: The Analysis of a Failure of American Diplomacy.

DTIC Science & Technology

1983-12-01

opportunity existed in the Middle East for the conclusion of an interim settlement in the dispute between Egypt and Israel. Egyptian President Anwar el -Sadat...Richard M. Nixon; Henry A. Kissinger; William P. Rogers; Joseph Sisco; Donald Bergus; Michael Sterner; Golda Meir; Abba Eban; Moshe Dayan; Anwar el ...for the conclusion of an interim settlement in the dispute between Egypt and Israel. Egyptian President Anwar el -Sadat declared his willingness to

Evaluation and Analysis of SEASAT-A Scanning Multichannel Microwave Radiometer (SSMR) Antenna Pattern Correction (APC) Algorithm. Sub-task 4: Interim Mode T Sub B Versus Cross and Nominal Mode T Sub B

NASA Technical Reports Server (NTRS)

Kitzis, J. L.; Kitzis, S. N.

1979-01-01

The brightness temperature data produced by the SMMR Antenna Pattern Correction algorithm are evaluated. The evaluation consists of: (1) a direct comparison of the outputs of the interim, cross, and nominal APC modes; (2) a refinement of the previously determined cos beta estimates; and (3) a comparison of the world brightness temperature (T sub B) map with actual SMMR measurements.

Global trends and variability in integrated water vapour from ground-based GPS data and atmospheric models

NASA Astrophysics Data System (ADS)

Bock, Olivier; Parracho, Ana; Bastin, Sophie; Hourdin, Frededic; Mellul, Lidia

2016-04-01

A high-quality, consistent, global, long-term dataset of integrated water vapour (IWV) was produced from Global Positioning System (GPS) measurements at more than 400 sites over the globe among which 120 sites have more than 15 years of data. The GPS delay data were converted to IWV using surface pressure and weighted mean temperature estimates from ERA-Interim reanalysis. A two-step screening method was developed to detect and remove outliers in the IWV data. It is based on: 1) GPS data processing information and delay formal errors, and 2) intercomparison with ERA-Interim reanalysis data. The GPS IWV data are also homogenized to correct for offsets due to instrumental changes and other unknown factors. The differential homogenization method uses ERA-Interim IWV as a reference. The resulting GPS data are used to document the mean distribution, the global trends and the variability of IWV over the period 1995-2010, and are analysed in coherence with precipitation and surface temperature data (from observations and ERA-Interim reanalysis). These data are also used to assess global climate model simulations extracted from the IPCC AR5 archive. Large coherent spatial patterns of moistening and drying are evidenced but significant discrepancies are also seen between GPS measurements, reanalysis and climate models in various regions. In terms of variability, the monthly mean anomalies are intercompared. The temporal correlation between GPS and the climate model simulations is overall quite small but the spatial variation of the magnitude of the anomalies is globally well simulated. GPS IWV data prove to be useful to validate global climate model simulations and highlight deficiencies in their representation of the water cycle.

Grants for nurse practitioner traineeship programs--PHS. Interim final regulations.

PubMed

1984-08-01

These regulations set forth requirements for grants to schools of nursing, medicine, and public health, to public or nonprofit private hospitals, and to other public or nonprofit private entities to meet the costs of traineeships for training nurse practitioners. A trainee must sign a commitment with the Secretary to practice full-time as a nurse practitioner in a primary medical care health manpower shortage area, designated under section 332 of the Public Health Service Act (the Act), for a period equal to 1 month for each month of traineeship support, after completion of the training. If this obligation is not fulfilled, a trainee must pay back traineeship support. The purpose of these regulations is to respond to the comments on the 1980 interim final regulations and to conform 42 CFR Part 57, Subpart AA, with the Paperwork Reduction Act of 1980, Pub. L. 96-511, and with the Omnibus Budget Reconciliation Act of 1981, Pub. L. 97-35, which requires, among other provisions, that the Secretary provide, by regulation, for the waiver or suspension of the repayment obligation under certain conditions. In addition, other minor changes have been made and Office of Management and Budget (OMB) numbers are cited in those sections which have approved reporting and recordkeeping requirements.

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

24 CFR 35.820 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.820 Section 35...-Possession Multifamily Property § 35.820 Interim controls. HUD shall conduct interim controls in accordance... accordance with § 35.815. Interim controls are considered completed when clearance is achieved in accordance...

Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240).

PubMed

Tewari, Krishnansu S; Sill, Michael W; Penson, Richard T; Huang, Helen; Ramondetta, Lois M; Landrum, Lisa M; Oaknin, Ana; Reid, Thomas J; Leitao, Mario M; Michael, Helen E; DiSaia, Philip J; Copeland, Larry J; Creasman, William T; Stehman, Frederick B; Brady, Mark F; Burger, Robert A; Thigpen, J Tate; Birrer, Michael J; Waggoner, Steven E; Moore, David H; Look, Katherine Y; Koh, Wui-Jin; Monk, Bradley J

2017-10-07

On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m 2 on day 1 or 2) plus paclitaxel (135 mg/m 2 or 175 mg/m 2 on day 1) or topotecan (0·75 mg/m 2 on days 1-3) plus paclitaxel (175 mg/m 2 on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062. Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 [0·37-1·10]; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 [0·66-1·05]; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No fistulas resulted in surgical emergencies, sepsis, or death. The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof-of-concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer. National Cancer Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Energy policy act transportation study: Interim report on natural gas flows and rates

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

NONE

1995-11-17

This report, Energy Policy Act Transportation Study: Interim Report on Natural Gas Flows and Rates, is the second in a series mandated by Title XIII, Section 1340, ``Establishment of Data Base and Study of Transportation Rates,`` of the Energy Policy Act of 1992 (P.L. 102--486). The first report Energy Policy Act Transportation Study: Availability of Data and Studies, was submitted to Congress in October 1993; it summarized data and studies that could be used to address the impact of legislative and regulatory actions on natural gas transportation rates and flow patterns. The current report presents an interim analysis of naturalmore » gas transportation rates and distribution patterns for the period from 1988 through 1994. A third and final report addressing the transportation rates and flows through 1997 is due to Congress in October 2000. This analysis relies on currently available data; no new data collection effort was undertaken. The need for the collection of additional data on transportation rates will be further addressed after this report, in consultation with the Congress, industry representatives, and in other public forums.« less

Pirfenidone for the treatment of Hermansky-Pudlak Syndrome pulmonary fibrosis

PubMed Central

O’Brien, Kevin; Troendle, James; Gochuico, Bernadette R.; Markello, Thomas C.; Salas, Jose; Cardona, Hilda; Yao, Jianhua; Bernardini, Isa; Hess, Richard; Gahl, William A.

2013-01-01

Hermansky-Pudlak syndrome (HPS) type is a rare disorder of oculocutaneous albinism, platelet dysfunction, and in some subtypes, fatal pulmonary fibrosis. There is no effective treatment for the pulmonary fibrosis except lung transplantation, but an initial trial using pirfenidone, an anti-fibrotic agent, showed promising results. The current, randomized, placebo-controlled, prospective, double-blind trial investigated the safety and efficacy of pirfenidone for mild to moderate HPS-1 and 4 pulmonary fibrosis. Subjects were evaluated every 4 months at the National Institutes of Health Clinical Center, and the primary outcome parameter was change in forced vital capacity using repeated measures analysis with random coefficients. Thirty-five subjects with HPS-1 pulmonary fibrosis were enrolled during a 4-year interval; 23 subjects received pirfenidone and 12 received placebo. Four subjects withdrew from the trial, 3 subjects died, and 10 serious adverse events were reported. Both groups experienced similar side effects, especially gastroesophageal reflux. Interim analysis of the primary outcome parameter, performed 12 months after 30 patients were enrolled, showed no statistical difference between the placebo and pirfenidone groups, and the study was stopped due to futility. There were no significant safety concerns. Other clinical trials are indicated to identify single or multiple drug regimens that may be effective in treatment for progressive HPS-1 pulmonary fibrosis. PMID:21420888

Flight set 360L007 (STS-33) insulation component. Volume 3: Final release

NASA Technical Reports Server (NTRS)

Hicken, Steve

1990-01-01

Volume 3 of this postfire report deals with the insulation component of the RSRM. The report is released twice for each flight set. The interim release contract date is on or before 60 days after the last field joint or nozzle to case joint is disassembled at KSC and contain the results of the KSC visual evaluation. The data contained in Volume 3 interim release supersedes the insulation data presented in the KSC 10 day report. The final release contract data is on or before 60 days after the last factory joint is disassembled at the Clearfield H-7 facility and contains the results of all visual evaluations and a thermal safety factor analysis. The data contained in the Volume 3 final release supersedes the interim release and the insulation data presented in the Clearfield 10 day report.

75 FR 984 - Draft Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

... Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites AGENCY... Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at Comprehensive Environmental Response... interim PRGs for dioxin in soil. These draft recommended interim PRGs were calculated using existing, peer...

Pediatric Hodgkin Lymphoma Treated at Cancer Institute, Chennai, India: Long-Term Outcome

PubMed Central

Dhanushkodi, Manikandan; Ganesan, Trivadi S.; Ganesan, Prasanth; Sundersingh, Shirley; Selvaluxmy, Ganesarajah; Swaminathan, Rajaraman; Rama, Ranganathan; Sagar, Tenali Gnana

2017-01-01

Purpose Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy. Outcomes for pediatric HL may vary between developed and developing countries for multiple reasons. This study was conducted to ascertain the outcomes of children with HL at our center and to identify risk factors for recurrent disease. Methods We analyzed the outcomes of 172 consecutive, previously untreated patients with pediatric HL presenting at our center from 2001 to 2010. Patients were treated with either adriamycin, bleomycin, vinblastine, and dacarbazine or adriamycin, bleomycin, vinblastine, cyclophosphamide, vincristine, prednisone, and procarbazine chemotherapy initially, and radiation to bulky sites or a single site of residual disease when appropriate. Results The median duration of follow-up was 77 months. The median age of the patients was 10 years; 127 (74%) of the 172 patients were male. The extent of disease was stage I and II in 59% of the patients. B symptoms were present in 32% of the patients, and 27% had bulky disease. The most common histologic subtype was mixed cellularity (45%). The 5-year overall survival (OS) and progression-free survival (PFS) of the entire cohort were 92.9% and 83.1%, respectively. The 5-year OS rates for patients with stage I, II, III, and IV were 96%, 94.7%, 84%, and 69.8%, respectively. On univariate analysis, advanced stage, response on interim radiologic assessment, and presence of B symptoms significantly predicted inferior PFS and OS. On multivariate analysis, only interim radiologic response significantly predicted PFS (P < .001) and OS (P < .001). Conclusion Overall, the outcomes of patients treated at our center are comparable to those observed in other centers in India and globally. PMID:29094094

Rolling out of kangaroo mother care in secondary level facilities in Bihar-Some experiences.

PubMed

Neogi, Sutapa B; Chauhan, Monika; Sharma, Jyoti; Negandhi, Preeti; Sethy, Ghanshyam

2016-01-01

Preterm birth is one of the leading causes of under-five child deaths worldwide and in India. Kangaroo mother care (KMC) is a powerful and easy-to-use method to promote health and well-being and reduce morbidity and mortality in preterm/low birth weight (LBW) babies. As the part of the roll-out of India Newborn Action Plan interventions, we implemented KMC in select facilities with an objective to assess the responsiveness of public health system to roll out KMC. KMC intervention was implemented in two select high priority districts, Gaya and Purnea in Bihar over the duration of 8 months from August 2015 to March 2016. The implementation of intervention was phased out into; situation analysis, implementation of intervention, and interim assessment. KMC model, as envisaged keeping in mind the building blocks of health system, was established in 6 identified health-care facilities. A pretested simple checklist was used to assess the awareness, knowledge, skills, and practice of KMC during baseline situational analysis and interim assessment phases for comparison. The intervention clearly seemed to improve the awareness among auxiliary nurse midwives/nurses about KMC. Improvements were also observed in the availability of infrastructure required for KMC and support logistics like facility for manual expression of breast milk, cups/suitable devices such as paladi cups for feeding small babies and digital weighing scale. Although the recording of information regarding LBW babies and KMC practice improved, still there is scope for much improvement. There is a commitment at the national level to promote KMC in every facility. The present experience shows the possibility of rolling out KMC in secondary level facilities with support from government functionaries.

Predicting clinical trial results based on announcements of interim analyses

PubMed Central

2014-01-01

Background Announcements of interim analyses of a clinical trial convey information about the results beyond the trial’s Data Safety Monitoring Board (DSMB). The amount of information conveyed may be minimal, but the fact that none of the trial’s stopping boundaries has been crossed implies that the experimental therapy is neither extremely effective nor hopeless. Predicting success of the ongoing trial is of interest to the trial’s sponsor, the medical community, pharmaceutical companies, and investors. We determine the probability of trial success by quantifying only the publicly available information from interim analyses of an ongoing trial. We illustrate our method in the context of the National Surgical Adjuvant Breast and Bowel (NSABP) trial, C-08. Methods We simulated trials based on the specifics of the NSABP C-08 protocol that were publicly available. We quantified the uncertainty around the treatment effect using prior weights for the various possibilities in light of other colon cancer studies and other studies of the investigational agent, bevacizumab. We considered alternative prior distributions. Results Subsequent to the trial’s third interim analysis, our predictive probabilities were: that the trial would eventually be successful, 48.0%; would stop for futility, 7.4%; and would continue to completion without statistical significance, 44.5%. The actual trial continued to completion without statistical significance. Conclusions Announcements of interim analyses provide information outside the DSMB’s sphere of confidentiality. This information is potentially helpful to clinical trial prognosticators. ‘Information leakage’ from standard interim analyses such as in NSABP C-08 is conventionally viewed as acceptable even though it may be quite revealing. Whether leakage from more aggressive types of adaptations is acceptable should be assessed at the design stage. PMID:24607270

Mapping probabilities of extreme continental water storage changes from space gravimetry

NASA Astrophysics Data System (ADS)

Kusche, J.; Eicker, A.; Forootan, E.; Springer, A.; Longuevergne, L.

2016-08-01

Using data from the Gravity Recovery And Climate Experiment (GRACE) mission, we derive statistically robust "hot spot" regions of high probability of peak anomalous—i.e., with respect to the seasonal cycle—water storage (of up to 0.7 m one-in-five-year return level) and flux (up to 0.14 m/month). Analysis of, and comparison with, up to 32 years of ERA-Interim reanalysis fields reveals generally good agreement of these hot spot regions to GRACE results and that most exceptions are located in the tropics. However, a simulation experiment reveals that differences observed by GRACE are statistically significant, and further error analysis suggests that by around the year 2020, it will be possible to detect temporal changes in the frequency of extreme total fluxes (i.e., combined effects of mainly precipitation and floods) for at least 10-20% of the continental area, assuming that we have a continuation of GRACE by its follow-up GRACE Follow-On (GRACE-FO) mission.

IUS/TUG orbital operations and mission support study. Volume 2: Interim upper stage operations

NASA Technical Reports Server (NTRS)

1975-01-01

Background data and study results are presented for the interim upper stage (IUS) operations phase of the IUS/tug orbital operations study. The study was conducted to develop IUS operational concepts and an IUS baseline operations plan, and to provide cost estimates for IUS operations. The approach used was to compile and evaluate baseline concepts, definitions, and system, and to use that data as a basis for the IUS operations phase definition, analysis, and costing analysis. Both expendable and reusable IUS configurations were analyzed and two autonomy levels were specified for each configuration. Topics discussed include on-orbit operations and interfaces with the orbiter, the tracking and data relay satellites and ground station support capability analysis, and flight control center sizing to support the IUS operations.

The use of group sequential, information-based sample size re-estimation in the design of the PRIMO study of chronic kidney disease.

PubMed

Pritchett, Yili; Jemiai, Yannis; Chang, Yuchiao; Bhan, Ishir; Agarwal, Rajiv; Zoccali, Carmine; Wanner, Christoph; Lloyd-Jones, Donald; Cannata-Andía, Jorge B; Thompson, Taylor; Appelbaum, Evan; Audhya, Paul; Andress, Dennis; Zhang, Wuyan; Solomon, Scott; Manning, Warren J; Thadhani, Ravi

2011-04-01

Chronic kidney disease is associated with a marked increase in risk for left ventricular hypertrophy and cardiovascular mortality compared with the general population. Therapy with vitamin D receptor activators has been linked with reduced mortality in chronic kidney disease and an improvement in left ventricular hypertrophy in animal studies. PRIMO (Paricalcitol capsules benefits in Renal failure Induced cardia MOrbidity) is a multinational, multicenter randomized controlled trial to assess the effects of paricalcitol (a selective vitamin D receptor activator) on mild to moderate left ventricular hypertrophy in patients with chronic kidney disease. Subjects with mild-moderate chronic kidney disease are randomized to paricalcitol or placebo after confirming left ventricular hypertrophy using a cardiac echocardiogram. Cardiac magnetic resonance imaging is then used to assess left ventricular mass index at baseline, 24 and 48 weeks, which is the primary efficacy endpoint of the study. Because of limited prior data to estimate sample size, a maximum information group sequential design with sample size re-estimation is implemented to allow sample size adjustment based on the nuisance parameter estimated using the interim data. An interim efficacy analysis is planned at a pre-specified time point conditioned on the status of enrollment. The decision to increase sample size depends on the observed treatment effect. A repeated measures analysis model, using available data at Week 24 and 48 with a backup model of an ANCOVA analyzing change from baseline to the final nonmissing observation, are pre-specified to evaluate the treatment effect. Gamma-family of spending function is employed to control family-wise Type I error rate as stopping for success is planned in the interim efficacy analysis. If enrollment is slower than anticipated, the smaller sample size used in the interim efficacy analysis and the greater percent of missing week 48 data might decrease the parameter estimation accuracy, either for the nuisance parameter or for the treatment effect, which might in turn affect the interim decision-making. The application of combining a group sequential design with a sample-size re-estimation in clinical trial design has the potential to improve efficiency and to increase the probability of trial success while ensuring integrity of the study.

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

40 CFR 57.803 - Issuance of tentative determination; notice.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determination. (1) The EPA staff shall formulate and prepare: (i) A “Staff Computational Analysis,” using the... Computational Analysis, discussing the estimated cost of interim controls, and assessing the effect upon the...

Filling the gaps in meteorological continuous data measured at FLUXNET sites with ERA-Interim reanalysis

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

Vuichard, N.; Papale, D.

In this study, exchanges of carbon, water and energy between the land surface and the atmosphere are monitored by eddy covariance technique at the ecosystem level. Currently, the FLUXNET database contains more than 500 registered sites, and up to 250 of them share data (free fair-use data set). Many modelling groups use the FLUXNET data set for evaluating ecosystem models' performance, but this requires uninterrupted time series for the meteorological variables used as input. Because original in situ data often contain gaps, from very short (few hours) up to relatively long (some months) ones, we develop a new and robustmore » method for filling the gaps in meteorological data measured at site level. Our approach has the benefit of making use of continuous data available globally (ERA-Interim) and a high temporal resolution spanning from 1989 to today. These data are, however, not measured at site level, and for this reason a method to downscale and correct the ERA-Interim data is needed. We apply this method to the level 4 data (L4) from the La Thuile collection, freely available after registration under a fair-use policy. The performance of the developed method varies across sites and is also function of the meteorological variable. On average over all sites, applying the bias correction method to the ERA-Interim data reduced the mismatch with the in situ data by 10 to 36 %, depending on the meteorological variable considered. In comparison to the internal variability of the in situ data, the root mean square error (RMSE) between the in situ data and the unbiased ERA-I (ERA-Interim) data remains relatively large (on average over all sites, from 27 to 76 % of the standard deviation of in situ data, depending on the meteorological variable considered). The performance of the method remains poor for the wind speed field, in particular regarding its capacity to conserve a standard deviation similar to the one measured at FLUXNET stations.« less

Filling the gaps in meteorological continuous data measured at FLUXNET sites with ERA-Interim reanalysis

DOE PAGES

Vuichard, N.; Papale, D.

2015-07-13

In this study, exchanges of carbon, water and energy between the land surface and the atmosphere are monitored by eddy covariance technique at the ecosystem level. Currently, the FLUXNET database contains more than 500 registered sites, and up to 250 of them share data (free fair-use data set). Many modelling groups use the FLUXNET data set for evaluating ecosystem models' performance, but this requires uninterrupted time series for the meteorological variables used as input. Because original in situ data often contain gaps, from very short (few hours) up to relatively long (some months) ones, we develop a new and robustmore » method for filling the gaps in meteorological data measured at site level. Our approach has the benefit of making use of continuous data available globally (ERA-Interim) and a high temporal resolution spanning from 1989 to today. These data are, however, not measured at site level, and for this reason a method to downscale and correct the ERA-Interim data is needed. We apply this method to the level 4 data (L4) from the La Thuile collection, freely available after registration under a fair-use policy. The performance of the developed method varies across sites and is also function of the meteorological variable. On average over all sites, applying the bias correction method to the ERA-Interim data reduced the mismatch with the in situ data by 10 to 36 %, depending on the meteorological variable considered. In comparison to the internal variability of the in situ data, the root mean square error (RMSE) between the in situ data and the unbiased ERA-I (ERA-Interim) data remains relatively large (on average over all sites, from 27 to 76 % of the standard deviation of in situ data, depending on the meteorological variable considered). The performance of the method remains poor for the wind speed field, in particular regarding its capacity to conserve a standard deviation similar to the one measured at FLUXNET stations.« less

A comparison of daily evaporation downscaled using WRFDA model and GLEAM dataset over the Iberian Peninsula.

NASA Astrophysics Data System (ADS)

José González-Rojí, Santos; Sáenz, Jon; Ibarra-Berastegi, Gabriel

2017-04-01

GLEAM dataset was presented a few years ago and since that moment, it has just been used for validation of evaporation in a few places of the world (Australia and Africa). The Iberian Peninsula is composed of different soil types and it is affected by different weather regimes, with different climate regions. It is this feature which makes it a very interesting zone for the study of the meteorological cycle, including evaporation. For that purpose, a numerical downscaling exercise over the Iberian Peninsula was run nesting the WRF model inside ERA Interim. Two model configurations were tested in two experiments spanning the period 2010-2014 after a one-year spin-up (2009). In the first experiment (N), boundary conditions drive the model. The second experiment (D) is configured the same way as the N case, but 3DVAR data assimilation is run every six hours (00Z, 06Z, 12Z and 18Z) using observations obtained from the PREPBUFR dataset. For both N and D runs and ERA Interim, the evaporation of the model runs was compared to GLEAM v3.0b and v3.0c datasets over the Iberian Peninsula, both at the daily and monthly time scales. GLEAM v3.0a was not used for validation as it uses for forcing radiation and air temperature data from ERA Interim. Results show that the experiment with data assimilation (D) improve the results obtained for N experiment. Moreover, correlations values are comparable to the ones obtained with ERA Interim. However, some negative correlation values are observed at Portuguese and Mediterranean coasts for both WRF runs. All of these problematic points are considered as urban sites by the NOAH land surface model. Because of that, the model is not able to simulate a correct evaporation value. Even with these discrepancies, better results than for ERA Interim are observed for seasonal Biases and daily RMSEs over Iberian Peninsula, obtaining the best values inland. Minimal differences are observed for the two GLEAM datasets selected.

Assessment of Proposed Cab Glass Coating for FAA Control Towers

DTIC Science & Technology

2015-11-16

report would be prepared after the initial coating and evaluation (with sprayed water) and then a final report after the 6 month study period to assess...Distribution A: Approved for public release. AFRL-RH-WP-TR-2015-0074 Assessment of Proposed Cab Glass Coating for FAA Control...REPORT TYPE Interim 3. DATES COVERED (From - To) 30 Jun 2014 – 1 Nov 2015 4. TITLE AND SUBTITLE Assessment of Proposed Cab Glass Coating

836: Developing a Cooperative Communication System for Safe, Effective, and Efficient Patient Care

DTIC Science & Technology

2014-01-01

since tool institution. There was an average rate of 40 positive sepsis identification tool (SIT) triggers per 1000 patient days. In a 6 month...period 28% of patients with a positive SIT had sepsis and 6% had severe sepsis. Interim review showed 67% received first fluid bolus within 20 minutes...for ulcer prevention, including changing the practice of positioning mechanically ventilated and sedated patients , rethinking the use of extended

An exploratory study of the health harms and utilisation of health services of frequent legal high users under the interim regulated legal high market in central Auckland.

PubMed

Wilkins, Chris; Prasad, Jitesh; Wong, K C; Rychert, Marta; Graydon-Guy, Thomas

2016-03-11

To explore health problems and the accessing of health services by frequent legal high users under an interim regulated legal market in central Auckland. Frequent legal high users (monthly+) were recruited from outside eight randomly-selected, licensed, legal high stores in central Auckland from 23 April-7 May, 2014. Eligible participants were emailed a unique invitation to complete an on-line survey; 105 completed the survey. Twenty-seven percent had suffered mental illness during their lifetimes. Eighty percent used synthetic cannabinoids (SC), and 20% 'party pills'. Forty-seven percent of SC users used daily or more often. Other drugs used included alcohol (80%), cannabis (59%), 'ecstasy' (18%) and methamphetamine (15%). Fifty-eight percent of SC users were classified as SC dependent. The most common problems reported from SC use were: insomnia (29%); 'vomiting/nausea' (25%); 'short temper/agitation' (21%); 'anxiety' (21%); 'strange thoughts' (16%); and 'heart palpitations' (14%). The health services most commonly accessed by SC users were: a 'doctor/GP' (9%); 'counsellor' (9%); 'DrugHelp/MethHelp' websites (7%); 'Alcohol & Drug Helpline' (4%); 'ambulance' (3%); 'A&E' (3%); and hospitalisation (3%). Frequent use of interim licensed SC products was associated with health problems, including dependency. Further research is required to determine the health risks of these products.

Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test.

PubMed

Hsueh, Eddy C; DeBloom, James R; Lee, Jonathan; Sussman, Jeffrey J; Covington, Kyle R; Middlebrook, Brooke; Johnson, Clare; Cook, Robert W; Slingluff, Craig L; McMasters, Kelly M

2017-08-29

A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS). Median follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18-87) and median Breslow thickness was 1.2 mm (range 0.2-12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each). Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01), while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis. Interim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP's ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients. ClinicalTrials.gov, NCT02355574  and NCT02355587.

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.

Impact of Short Daily Hemodialysis on Restless Legs Symptoms and Sleep Disturbances

PubMed Central

Schiller, Brigitte; Burkart, John M.; Daoui, Rachid; Kraus, Michael A.; Lee, Yoojin; Miller, Brent W.; Teitelbaum, Isaac; Williams, Amy W.; Finkelstein, Fredric O.

2011-01-01

Summary Background and objectives Restless legs syndrome (RLS) and sleep disturbances are common among in-center hemodialysis patients and are associated with increased morbidity/mortality. Design, setting, participants, & measurements The FREEDOM study is an ongoing prospective cohort study investigating the benefits of home short daily hemodialysis (SDHD) (6 times/week). In this interim report, we examine the long-term effect of SDHD on the prevalence and severity of RLS, as measured by the International Restless Legs Syndrome (IRLS) Study Group rating scale, and sleep disturbances, as measured by the Medical Outcomes Study sleep survey. Results 235 participants were included in this report (intention-to-treat cohort), of which 127 completed the 12-month follow-up (per-protocol cohort). Mean age was 52 years, 55% had an arteriovenous fistula, and 40% suffered from RLS. In the per-protocol analysis, among patients with RLS, the mean IRLS score improved significantly at month 12, after adjustment for use of RLS-related medications (18 versus 11). Among patients with moderate-to-severe RLS (IRLS score ≥15), there was an even greater improvement in the IRLS score (23 versus 13). The intention-to-treat analysis yielded similar results. Over 12 months, there was decline in the percentage of patients reporting RLS (35% versus 26%) and those reporting moderate-to-severe RLS (59% versus 43%). There was a similar and sustained 12-month improvement in several scales of the sleep survey, after adjustment for presence of RLS and use of anxiolytics and hypnotics. Conclusions Home SDHD is associated with long-term improvement in the prevalence and severity of RLS and sleep disturbances. PMID:21415315

Flight Set 360T004 (STS-30) Insulation Component, Interim Release, Volume 3

NASA Technical Reports Server (NTRS)

Passman, James A.

1989-01-01

The insulation component of the Redesigned Solid Rocket Motor (RSRM) is discussed. The results of all visual evaluations and a thermal safety factor analysis are given. The data contained here supersedes the interim release and the insulation data presented in the Clearfield 10 day report. The objective is to document the postflight condition of the internal and external insulation of nozzle to case joints, the case field joints, the igniter to case joints, and the acreage insulation which made up RSRM-4A and RSRM-4B.

Interim Calibration Report for the SMMR Simulator

NASA Technical Reports Server (NTRS)

Gloersen, P.; Cavalieri, D.

1979-01-01

The calibration data obtained during the fall 1978 Nimbus-G underflight mission with the scanning multichannel microwave radiometer (SMMR) simulator on board the NASA CV-990 aircraft were analyzed and an interim calibration algorithm was developed. Data selected for the analysis consisted of in flight sky, first-year sea ice, and open water observations, as well as ground based observations of fixed targets with varied temperatures of selected instrument components. For most of the SMMR channels, a good fit to the selected data set was obtained with the algorithm.

Exploring the Links in Monthly to Decadal Variability of the Atmospheric Water Balance Over the Wettest Regions in ERA-20C

NASA Astrophysics Data System (ADS)

Nogueira, M.

2017-10-01

Monthly-to-decadal variability of the regional precipitation over Intertropical Convergence Zone and north-Atlantic and north-Pacific storm tracks was investigated using ERA-20C reanalysis. Satellite-based precipitation (P) and evaporation (E) climatological patterns were well reproduced by ERA-20C. Regional P and E monthly time series displayed 20% differences, but these decreased rapidly with time scale ( 10% at yearly time scales). Spectral analysis showed good scale-by-scale statistical agreement between ERA-20C and observations. Using ERA-Interim showed no improvement despite the much wider range of information assimilated (including satellites). Remarkably high Detrended Cross-Correlation Analysis coefficients (ρDCCA > 0.7 and often ρDCCA > 0.9) revealed tight links between the nonperiodic variability of P, moisture divergence (DIV), and pressure velocity (ω) at monthly-to-decadal time scales over all the wet regions. In contrast, ρDCCA was essentially nonsignificant between nonperiodic P and E or sea surface temperature (SST). Thus, the nonperiodic monthly-to-decadal variability of precipitation in these regions is almost fully controlled by dynamics and not by local E or SST (suggested by Clausius-Clapeyron relation). Analysis of regional nonperiodic standard deviations and power spectra (and respective spectral exponents, β) provided further robustness to this conclusion. Finally, clear transitions in β for P, DIV, and ω between tropical and storm track regions were found. The latter is dominated by transient storms, with energy accumulation at synoptic scales and β < 0.1 at monthly-to-decadal time scales, implying that variability and information creation decrease rapidly with time scale. Larger β values (0.2 to 0.4) were found in the tropics, implying longer-range autocorrelations and slower decreasing variability and information creation with time scale, consistent with the important forcing from internal modes of variability (e.g., El Niño-Southern Oscillation).

IVHS Countermeasures for Rear-End Collision, Task 1 Vol. V: 1985 NASS Case Analysis

DOT National Transportation Integrated Search

1994-02-15

The Task 1 Interim Report consists of six volumes. This Volume, Volume V, 1985 NASS Analysis, presents the results of the analysis of the 1985 NASS crash data. Data from 1985 was selected for analysis because it provided more insight into roadway var...

Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

PubMed

Saida, Takahiko; Yokoyama, Kazumasa; Sato, Ryusuke; Makioka, Haruki; Iizuka, Yukihiko; Hase, Masakazu; Ling, Yan; Torii, Shinichi

2017-12-01

Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis. During the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs). The safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing-remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period. The safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation. Biogen Japan Ltd (Tokyo, Japan).

Analysis of extreme summers and prior late winter/spring conditions in central Europe

NASA Astrophysics Data System (ADS)

Träger-Chatterjee, C.; Müller, R. W.; Bendix, J.

2013-05-01

Drought and heat waves during summer in mid-latitudes are a serious threat to human health and agriculture and have negative impacts on the infrastructure, such as problems in energy supply. The appearance of such extreme events is expected to increase with the progress of global warming. A better understanding of the development of extremely hot and dry summers and the identification of possible precursors could help improve existing seasonal forecasts in this regard, and could possibly lead to the development of early warning methods. The development of extremely hot and dry summer seasons in central Europe is attributed to a combined effect of the dominance of anticyclonic weather regimes and soil moisture-atmosphere interactions. The atmospheric circulation largely determines the amount of solar irradiation and the amount of precipitation in an area. These two variables are themselves major factors controlling the soil moisture. Thus, solar irradiation and precipitation are used as proxies to analyse extreme sunny and dry late winter/spring and summer seasons for the period 1958-2011 in Germany and adjacent areas. For this purpose, solar irradiation data from the European Center for Medium Range Weather Forecast 40-yr and interim re-analysis dataset, as well as remote sensing data are used. Precipitation data are taken from the Global Precipitation Climatology Project. To analyse the atmospheric circulation geopotential data at 850 hPa are also taken from the European Center for Medium Range Weather Forecast 40-yr and interim re-analysis datasets. For the years in which extreme summers in terms of high solar irradiation and low precipitation are identified, the previous late winter/spring conditions of solar irradiation and precipitation in Germany and adjacent areas are analysed. Results show that if the El Niño-Southern Oscillation (ENSO) is not very intensely developed, extremely high solar irradiation amounts, together with extremely low precipitation amounts during late winter/spring, might serve as precursor of extremely sunny and dry summer months to be expected.

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

PubMed Central

Wolff, Antonio C.; Lazar, Ann A.; Bondarenko, Igor; Garin, August M.; Brincat, Stephen; Chow, Louis; Sun, Yan; Neskovic-Konstantinovic, Zora; Guimaraes, Rodrigo C.; Fumoleau, Pierre; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

2013-01-01

Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation. PMID:23233719

5 CFR 772.102 - Interim personnel actions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Interim personnel actions. 772.102 Section 772.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.102 Interim personnel actions. When an employee or...

5 CFR 772.102 - Interim personnel actions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interim personnel actions. 772.102 Section 772.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) INTERIM RELIEF General § 772.102 Interim personnel actions. When an employee or...

Certification and verification for Northrup model NSC-01-0732 fresnel lens concentrating solar collector

NASA Technical Reports Server (NTRS)

1979-01-01

Structural analysis and certification of the collector system is presented. System verification against the interim performance criteria is presented and indicated by matrices. The verification discussion, analysis, and test results are also given.

Interim Expertise

ERIC Educational Resources Information Center

Anyaso, Hilary Hurd

2009-01-01

The Registry for College and University Presidents places former executives in interim presidential and other senior-level posts and is familiar with the challenges interim executives and institutions encounter in times of leadership transitions. However, the one big advantage interims bring to institutions, says Registry Vice President Kevin J.…

40 CFR 155.56 - Interim registration review decision.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Interim registration review decision... PROGRAMS REGISTRATION STANDARDS AND REGISTRATION REVIEW Registration Review Procedures § 155.56 Interim registration review decision. The Agency may issue, when it determines it to be appropriate, an interim...

Manufacturing Technology for Apparel Automation. Phases 1 and 2.

DTIC Science & Technology

1987-07-15

Modularized Work Unit Groups . . . . . . . 12 i +,. :.Aooesston For :".. NTIS GR.AA1 ’- " "D T I C T A B Unannounced [] ~Justification i Availability...The monthly interim reports are summarized in this semiannual report. Activity to date has included work performed by Ms. Carol Carrere Dr. T. G. Clapp...Management. Provide, in accordance with paragraph 3.1 of the Statement of Work (SOW), North Carolina State University’s Technical Proposal, Manufacturing

Empowerment, PTSD and revictimization among women who have experienced intimate partner violence.

PubMed

Dardis, Christina M; Dichter, Melissa E; Iverson, Katherine M

2018-08-01

Empowerment is associated with lower posttraumatic stress disorder (PTSD) symptoms and intimate partner violence (IPV) revictimization, but the direction of these associations remains unknown. Two models were assessed: one in which empowerment is protective against future IPV revictimization and PTSD symptoms, and one in which PTSD symptoms lead to reductions in empowerment and increases in IPV revictimization. Drawn from a probability-based access survey panel of U.S. adults, the present sample included 101 women veterans who experienced past-year IPV. Baseline demographics were assessed (T0), with surveys conducted at Time 1 (T1; 18-month interim), and Time 2 (T2; 6-month interim). Cross-lagged panel models assessed the two models separately among women who reported only T1 psychological IPV victimization (58%) and women who reported T1 physical and/or sexual IPV victimization. Among psychological IPV victims, T1 empowerment was significantly associated with decreased T2 PTSD symptoms, whereas among women who reported physical and/or sexual IPV victimization, T1 empowerment was significantly associated with decreased T2 IPV revictimization. The model in which PTSD symptoms confer risk for lower empowerment was not supported; however, higher T1 PTSD symptoms were associated with increased IPV revictimization among women who reported psychological IPV only. Findings can inform interventions for IPV survivors. Copyright © 2018 Elsevier B.V. All rights reserved.

Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group.

PubMed

Borchmann, Peter; Haverkamp, Heinz; Lohri, Andreas; Mey, Ulrich; Kreissl, Stefanie; Greil, Richard; Markova, Jana; Feuring-Buske, Michaela; Meissner, Julia; Dührsen, Ulrich; Ostermann, Helmut; Keller, Ulrich; Maschmeyer, Georg; Kuhnert, Georg; Dietlein, Markus; Kobe, Carsten; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Diehl, Volker; Engert, Andreas

2017-04-01

Advanced stage Hodgkin's lymphoma represents a heterogeneous group of patients with different risk profiles. Data suggests that interim PET assessment during chemotherapy is superior to baseline international prognostic scoring in terms of predicting long-term treatment outcome in patients with Hodgkin's lymphoma. We therefore hypothesised that early interim PET-imaging after two courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) might be suitable for guiding treatment in patients with advanced stage Hodgkin's lymphoma. We aimed to assess whether intensifying standard chemotherapy (BEACOPP escalated ) by adding rituximab would improve progression-free survival in patients with positive PET after two courses of chemotherapy. In this open-label, international, randomised, phase 3 study, we recruited patients aged 18-60 years with newly diagnosed, advanced stage Hodgkin's lymphoma from 160 hospitals and 77 private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. Interim PET-imaging was done after two cycles of BEACOPP escalated and centrally assessed by an expert panel. Patients with a positive PET after 2 cycles of BEACOPP escalated chemotherapy (PET-2) were randomly assigned (1:1) to receive six additional courses of either BEACOPP escalated (BEACOPP escalated group) or BEACOPP escalated plus rituximab (R-BEACOPP escalated group). PET-2 was assessed using a 5-point scale with 18 FDG uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3) defined as positive. BEACOPP escalated was given as previously described; rituximab was given intravenously at a dose of 375 mg/m 2 (maximum total dose 700 mg), the first administration starting 24 h before starting the fourth cycle of BEACOPP escalated (day 0 and day 3 in cycle 4, day 1 in cycles 5-8). Randomisation was done centrally and used the minimisation method including a random component, stratified according to centre, age, stage, international prognostic score, and sex. The primary efficacy endpoint was 5 year progression-free survival, analysed in the intention-to-treat population. We are reporting this second planned interim analysis as the final report of the trial. The trial is registered with ClinicalTrials.gov, number NCT00515554. Between May 14, 2008, and May 31, 2011, we enrolled 1100 patients. 440 patients had a positive PET-2 and were randomly assigned to either the BEACOPP escalated group (n=220) or the R-BEACOPP escalated group (n=220). With a median follow-up of 33 months (IQR 25-42) for progression-free survival, estimated 3 year progression-free survival was 91·4% (95% CI 87·0-95·7) for patients in the BEACOPP escalated group and 93·0% (89·4-96·6) for those in the R-BEACOPP escalated group (difference 1·6%, 95% CI -4·0 to 7·3; log rank p=0·99). Common grade 3-4 adverse events were leucopenia (207 [95%] of 218 patients in the BEACOPP escalated group vs 211 [96%] of 220 patients in the R-BEACOPP escalated group), and severe infections (51 [23%] vs 43 [20%] patients). Based on a futility analysis, the independent data monitoring committee recommended publication of this second planned interim analysis as the final result. Six (3%) of 219 patients in the BEACOPP escalated group and ten (5%) of 220 in the R-BEACOPP escalated group died; fatal treatment-related toxic effects occurred in one (<1%) patient in the BEACOPP escalated group and three (1%) in the R-BEACOPP escalated group, all of them due to infection. The addition of rituximab to BEACOPP escalated did not improve the progression-free survival of PET-2 positive patients with advanced stage Hodgkin's lymphoma. However, progression-free survival for PET-2 positive patients was much better than expected, exceeding even the outcome of PET-2-unselected patients in the previous HD15 trial. Thus, PET-2 cannot identify patients at high-risk for treatment failure in the context of the very effective German Hodgkin Study Group standard treatment for advanced stage Hodgkin's lymphoma. Deutsche Krebshilfe; Swiss State Secretariat for Education, Research and Innovation (SERI); and Roche Pharma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of SST anomalies in low latitudes on atmospheric heat transport to the Arctic

NASA Astrophysics Data System (ADS)

Alekseev, Genrikh; Kuzmina, Svetlana; Glok, Natalia

2017-04-01

The purpose of the study is to assess the influence of SST anomalies in the low latitudes of the Atlantic, Indian and Pacific oceans to climatic change of the winter atmospheric meridional heat transport (MAHT) to the Arctic and to propose the mechanisms of this influence. Estimates of sensible and latent heat transport to the Arctic through the "Atlantic Gate" at 70 ° N in winter (December-February) 1980-2015 fulfilled on base ERA / Interim and monthly SST from HadISST were used. Multi-dimensional cross-correlation analysis was applied. The area and month in each ocean were found with maximal correlations between SST and winter MAHT. Mean SST in selected areas for each month of 1980-2015 were calculated and its correlations with MAHT were estimated. The correlation coefficients equal from 0.57 to 0.42, and after removing the noise increased up to 0.75 with MAHT lag from 27 to 30 months. The SST and MAHT series include together with positive trend the 5-7 years fluctuations. The mechanism of SST anomalies influence on winter MAHT to the Arctic includes the interaction of atmospheric (Hadley and Ferrel circulations, jet streams, NAO) and oceanic (Gulf Stream, the North Atlantic, the Norwegian currents) circulation patterns. To justify the proposed scheme the evaluation of the links between SST anomalies, the NAO index, the Atlantic water inflow to the Barents Sea, are investigated. The study is supported with RFBR project 15-05-03512.

17 CFR 210.8-03 - Interim financial statements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (§ 249.308(a) of this chapter) must be reviewed by an independent public accountant using professional... interim financial statements have been reviewed by an independent public accountant, a report of the accountant on the review must be filed with the interim financial statements. Interim financial statements...

24 CFR 35.1330 - Interim controls.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Interim controls. 35.1330 Section... Lead-Paint Hazard Evaluation and Hazard Reduction Activities § 35.1330 Interim controls. Interim controls of lead-based paint hazards identified in a risk assessment shall be conducted in accordance with...

7 CFR 1738.21 - Interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1738.21 Section 1738.21... Interim financing. (a) Upon notification by RUS that an applicant's application is considered complete, the applicant may enter into an interim financing agreement with a lender other than RUS or use its...

An Approach for Evaluating the Technical Quality of Interim Assessments

ERIC Educational Resources Information Center

Li, Ying; Marion, Scott; Perie, Marianne; Gong, Brian

2010-01-01

Increasing numbers of schools and districts have expressed interest in interim assessment systems to prepare for summative assessments and to improve teaching and learning. However, with so many commercial interim assessments available, schools and districts are struggling to determine which interim assessment is most appropriate to their needs.…

47 CFR 51.611 - Interim wholesale rates.

Code of Federal Regulations, 2010 CFR

2010-10-01

... selecting a particular discount rate. The same discount percentage rate shall be used to establish interim... 47 Telecommunication 3 2010-10-01 2010-10-01 false Interim wholesale rates. 51.611 Section 51.611... Resale § 51.611 Interim wholesale rates. (a) If a state commission cannot, based on the information...

7 CFR 15a.71 - Interim procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Interim procedures. 15a.71 Section 15a.71 Agriculture Office of the Secretary of Agriculture EDUCATION PROGRAMS OR ACTIVITIES RECEIVING OR BENEFITTING FROM FEDERAL FINANCIAL ASSISTANCE Procedures (Interim) § 15a.71 Interim procedures. For the purposes of...

77 FR 55230 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-01; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0068] Japan Lessons-Learned Project Directorate Interim... Commission (NRC). ACTION: Japan Lessons-Learned Project Directorate interim staff guidance; issuance. SUMMARY...-Learned Project Directorate Interim Staff Guidance (JLD-ISG), JLD-ISG-2012-01, ``Compliance with Order EA...

77 FR 55231 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-02; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0069] Japan Lessons-Learned Project Directorate Interim...-Learned Project Directorate interim staff guidance; issuance. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing the Final Japan Lessons-Learned Project Directorate Interim...

7 CFR 1735.75 - Interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Interim financing. 1735.75 Section 1735.75... Involving Loan Funds § 1735.75 Interim financing. (a) A borrower may submit a written request for RUS approval of interim financing if it is necessary to close an acquisition before the loan to finance the...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2014 CFR

2014-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2010 CFR

2010-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2013 CFR

2013-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2012 CFR

2012-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

13 CFR 120.890 - Source of interim financing.

Code of Federal Regulations, 2011 CFR

2011-01-01

....890 Section 120.890 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Interim Financing § 120.890 Source of interim financing. A Project may... experience or qualifications, SBA may require the interim loan to be managed by a third party such as a bank...

Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting.

PubMed

Dal-Ré, Rafael; Ross, Joseph S; Marušić, Ana

2016-07-01

To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 13610 - Office of New Reactors; Interim Staff Guidance on Implementation of a Seismic Margin Analysis for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... Staff Guidance on Implementation of a Seismic Margin Analysis for New Reactors Based on Probabilistic... Seismic Margin Analysis for New Reactors Based on Probabilistic Risk Assessment,'' (Agencywide Documents.../COL-ISG-020 ``Implementation of a Seismic Margin Analysis for New Reactors Based on Probabilistic Risk...

Treatment of posttraumatic reflex sympathetic dystrophy syndrome (RSDS) with intravenous blocks of a mixture of corticosteroid and lidocaine: a retrospective review of 17 consecutive cases.

PubMed

Tountas, A A; Noguchi, A

1991-01-01

Seventeen consecutive patients with posttraumatic reflex sympathetic dystrophy syndrome (RSDS) were treated with one or more regional i.v. blocks of methylprednisolone sodium succinate and lidocaine HCL after physical therapy and oral medications had failed to produce satisfactory relief of their symptoms. In 12 of these patients the upper extremity was affected, and in five, it was the lower extremity. A fracture of the distal radius was the most frequent predisposing event. The average delay between injury and the manifestation of RSDS was 2.5 months (range 2 days to almost 6 months). The index treatment in all cases started within 3 months of the onset of symptoms. The number of i.v. blocks given ranged from one to four (average 2.4). The side effects and complications were negligible. The treatment, which in most cases was given exclusively on an outpatient basis, was well tolerated by all patients except one. Assessment of 16 of them at 6 months showed that 11 had total or almost total relief of their symptoms. When 15 of the patients were reassessed at an average follow-up of 28 months (range 12-48 months), it was noted that none of the patients with an early satisfactory response experienced recurrence of their symptoms. The condition of the symptomatic patients in the interim had improved overall. Analysis of the cases with an unsatisfactory outcome suggested that the primary reason for failure was inadequate treatment rather than ineffectiveness of the treatment used. It was concluded that this method is simple, safe, and well tolerated and should be regarded as a first choice for posttraumatic RSDS.

Abiraterone and increased survival in metastatic prostate cancer.

PubMed

de Bono, Johann S; Logothetis, Christopher J; Molina, Arturo; Fizazi, Karim; North, Scott; Chu, Luis; Chi, Kim N; Jones, Robert J; Goodman, Oscar B; Saad, Fred; Staffurth, John N; Mainwaring, Paul; Harland, Stephen; Flaig, Thomas W; Hutson, Thomas E; Cheng, Tina; Patterson, Helen; Hainsworth, John D; Ryan, Charles J; Sternberg, Cora N; Ellard, Susan L; Fléchon, Aude; Saleh, Mansoor; Scholz, Mark; Efstathiou, Eleni; Zivi, Andrea; Bianchini, Diletta; Loriot, Yohann; Chieffo, Nicole; Kheoh, Thian; Haqq, Christopher M; Scher, Howard I

2011-05-26

Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group. The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).

Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study.

PubMed

Li, Wenhua; Zhao, Xiaoying; Wang, Huijie; Liu, Xin; Zhao, Xinmin; Huang, Mingzhu; Qiu, Lixin; Zhang, Wen; Chen, Zhiyu; Guo, Weijian; Li, Jin; Zhu, Xiaodong

2017-06-06

Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy. Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety. The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (< 120 g/L) was associated with poorer PFS with maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%). This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

Comparative Analysis of Languages for Machine Processing. Interim Report.

ERIC Educational Resources Information Center

Zierer, Ernesto; And Others

This report gives the results obtained in the semantic and syntactic analysis of the Japanese particles "de,""ni,""e," and "wo" in comparison to their equivalents in English, German, and Spanish. The study is based on the so-called "Correlational Analysis" as proposed by Ernst von Glaserfeld. The…

Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

PubMed

Diéras, Véronique; Miles, David; Verma, Sunil; Pegram, Mark; Welslau, Manfred; Baselga, José; Krop, Ian E; Blackwell, Kim; Hoersch, Silke; Xu, Jin; Green, Marjorie; Gianni, Luca

2017-06-01

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m 2 self-administered orally twice daily on days 1-14 on each 21-day cycle, plus lapatinib 1250 mg orally once daily on days 1-21). Randomisation was stratified by world region (USA vs western Europe vs or other), number of previous chemotherapy regimens for unresectable, locally advanced, or metastatic disease (0 or 1 vs >1), and disease involvement (visceral vs non-visceral). The coprimary efficacy endpoints were progression-free survival (per independent review committee assessment) and overall survival. Efficacy was analysed in the intention-to-treat population; safety was analysed in all patients who received at least one dose of study treatment, with patients analysed according to the treatment actually received. On May 30, 2012, the study protocol was amended to allow crossover from control to trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified overall survival efficacy boundary. This study is registered with ClinicalTrials.gov, number NCT00829166. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]). This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Droughts and Excessive Moisture Events in Southern Siberia in the Late XXth - Early XXIst Centuries

NASA Astrophysics Data System (ADS)

Ryazanova, A. A.; Voropay, N. N.

2017-11-01

In recent years much research has been devoted to global and regional climate changes. Special attention was paid to climate extremes, such as droughts and excessive moisture events. In this study the moisture and aridity of Southern Siberia are estimated using web-GIS called “CLIMATE”. The system “CLIMATE” is part of a hardware and software cloud storage complex for data analysis of various climatic data sets, with algorithms for searching, extracting, processing, and visualizing the data. The ECMWF ERA-Interim reanalysis data for Southern Siberia (50-65°N, 60-120°E) from 1979 to 2010 with a grid cell of 0.75×0.75° is used. Some hydrothermal conditions are estimated using the so-called Ped index (Si), which is a normalized indicator of the ratio of air temperature to precipitation. The mountain regions of Eastern Siberia are becoming more and more arid each month during the last 30 years. In Western Siberia, aridity increases in May and decreases in June, in the other months positive and negative trends are found. The greatest differences between the trends of the aridity index (Si), air temperature, and precipitation are observed in July.

Steps towards a consistent Climate Forecast System Reanalysis wave hindcast (1979-2016)

NASA Astrophysics Data System (ADS)

Stopa, Justin E.; Ardhuin, Fabrice; Huchet, Marion; Accensi, Mickael

2017-04-01

Surface gravity waves are being increasingly recognized as playing an important role within the climate system. Wave hindcasts and reanalysis products of long time series (>30 years) have been instrumental in understanding and describing the wave climate for the past several decades and have allowed a better understanding of extreme waves and inter-annual variability. Wave hindcasts have the advantage of covering the oceans in higher space-time resolution than possible with conventional observations from satellites and buoys. Wave reanalysis systems like ECWMF's ERA-Interim directly included a wave model that is coupled to the ocean and atmosphere, otherwise reanalysis wind fields are used to drive a wave model to reproduce the wave field in long time series. The ERA Interim dataset is consistent in time, but cannot adequately resolve extreme waves. On the other hand, the NCEP Climate Forecast System (CFSR) wind field better resolves the extreme wind speeds, but suffers from discontinuous features in time which are due to the quantity and quality of the remote sensing data incorporated into the product. Therefore, a consistent hindcast that resolves the extreme waves still alludes us limiting our understanding of the wave climate. In this study, we systematically correct the CFSR wind field to reproduce a homogeneous wave field in time. To verify the homogeneity of our hindcast we compute error metrics on a monthly basis using the observations from a merged altimeter wave database which has been calibrated and quality controlled from 1985-2016. Before 1985 only few wave observations exist and are limited to a select number of wave buoys mostly in the North Hemisphere. Therefore we supplement our wave observations with seismic data which responds to nonlinear wave interactions created by opposing waves with nearly equal wavenumbers. Within the CFSR wave hindcast, we find both spatial and temporal discontinuities in the error metrics. The Southern Hemisphere often has wind speed biases larger than the Northern Hemisphere and we propose a simple correction to reduce these features by applying a taper shaped by a half-Hanning window. The discontinuous features in time are corrected by scaling the entire wind field by percentages ranging typically ranging from 1-3%. Our analysis is performed on monthly time series and we expect the monthly statistics to be more adequate for climate studies.

Data Analysis of GPM Constellation Satellites-IMERG and ERA-Interim precipitation products over West of Iran

NASA Astrophysics Data System (ADS)

Sharifi, Ehsan; Steinacker, Reinhold; Saghafian, Bahram

2016-04-01

Precipitation is a critical component of the Earth's hydrological cycle. The primary requirement in precipitation measurement is to know where and how much precipitation is falling at any given time. Especially in data sparse regions with insufficient radar coverage, satellite information can provide a spatial and temporal context. Nonetheless, evaluation of satellite precipitation is essential prior to operational use. This is why many previous studies are devoted to the validation of satellite estimation. Accurate quantitative precipitation estimation over mountainous basins is of great importance because of their susceptibility to hazards. In situ observations over mountainous areas are mostly limited, but currently available satellite precipitation products can potentially provide the precipitation estimation needed for meteorological and hydrological applications. One of the newest and blended methods that use multi-satellites and multi-sensors has been developed for estimating global precipitation. The considered data set known as Integrated Multi-satellitE Retrievals (IMERG) for GPM (Global Precipitation Measurement) is routinely produced by the GPM constellation satellites. Moreover, recent efforts have been put into the improvement of the precipitation products derived from reanalysis systems, which has led to significant progress. One of the best and a worldwide used model is developed by the European Centre for Medium Range Weather Forecasts (ECMWF). They have produced global reanalysis daily precipitation, known as ERA-Interim. This study has evaluated one year of precipitation data from the GPM-IMERG and ERA-Interim reanalysis daily time series over West of Iran. IMERG and ERA-Interim yield underestimate the observed values while IMERG underestimated slightly and performed better when precipitation is greater than 10mm. Furthermore, with respect to evaluation of probability of detection (POD), threat score (TS), false alarm ratio (FAR) and probability of false detection (POFD) IMERG yields a better value of POD, TS, FAR and POFD in comparison to era-Interim. Overall, ERA-Interim product produced fewer robust results when compared to IMERG.

MUC-4 Test Results and Analysis

DTIC Science & Technology

1992-01-01

PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 MUC3 MUC4 STEMS 15,285 INFLECTED FORMS 14,56 1 TOTALS est at 10,000...34 . As an indication of system development during MUC4 , we can compare our TST3 results with our results on th e MUC-4 interim test (TST2) . The relevant... MUC4 Interim Test) Summary Scores SLOT POS ACT COR PAR INC ICR IPA SPU MIS NON REC PRE OVG inc-total 529 1189 160 63 24 0 23 942 282 718 36 16 79 perp

12 CFR 552.2-2 - Procedures for organization of interim Federal stock association.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Procedures for organization of interim Federal stock association. (a) Applications for permission to organize... chapter or § 552.2-1(b)(3) of this part. (b) Approval of an application for permission to organize an... the interim was chartered to facilitate. Applications for permission to organize an interim Federal...

Detailed Skylab ECS consumables analysis for the interim revision flight plan (November, 1972, SL-1 launch)

NASA Technical Reports Server (NTRS)

Wells, C.; Kolkhorst, H. E.

1971-01-01

The consumables analysis was performed for the Skylab 2, 3, and 4 Preliminary Reference Interim Revision Flight Plan. The analysis and the results are based on the mission requirements as specified in the flight plan and on other available data. The results indicate that the consumables requirements for the Skylab missions allow for remaining margins (percent) of oxygen, nitrogen, and water nominal as follows: 83.5, 90.8, and 88.7 for mission SL-2; 57.1, 64.1, and 67.3 for SL-3; and 30.8, 44.3, and 46.5 for SL-4. Performance of experiment M509 as scheduled in the flight plan results in venting overboard the cluster atmosphere. This is due to the addition of nitrogen for propulsion and to the additional oxygen introduced into the cabin when the experiment is performed with the crewman suited.

Impact evaluation of Morgantown PRT 1975-1976 ridership: Interim Analysis

DOT National Transportation Integrated Search

1977-06-01

An analysis of the ridership levels of the Morgantown PRT system during its : initial period of operation, the 1975-1976 academic year, is presented. PRT ridership : by day, weekly ridership trends in terms of exogeneous events, the influence of : fe...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

40 CFR 265.13 - General waste analysis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false General waste analysis. 265.13 Section 265.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL...

Interim analysis report : model deployment of a regional, multi-modal 511 traveler information system

DOT National Transportation Integrated Search

2004-02-17

This document presents the results of the analysis of baseline, or "pre-enhancement," data describing the operation of the existing 511 telephone traveler information system operated by the Arizona Department of Transportation (ADOT). The model deplo...

Brief Intervention for Truant Youth Sexual Risk Behavior and Alcohol Use: A Parallel Process Growth Model Analysis

PubMed Central

Dembo, Richard; Briones-Robinson, Rhissa; Ungaro, Rocio; Barrett, Kimberly; Gulledge, Laura; Winters, Ken C.; Belenko, Steven; Karas, Lora M.; Wareham, Jennifer

2011-01-01

Truant youths represent a challenging, yet very promising group of at-risk youth to study. In addition to problems in school, they frequently experience troubled family situations, emotional/ psychological problems, involvement in substance use, and delinquency. Given the problems often experienced by truant youth, it is likely they are engaging in alcohol use and sexual risk behavior at a higher rate, than the general youth population. Identification of these youths’ problems and early placement into effective intervention services would benefit them, their families, and society. The current study presents interim findings from an ongoing, NIDA-funded experimental, Brief Intervention (BI) study involving truant youths and their parent/guardians. Baseline, 3-month, 6-month, and 12-month follow up data were analyzed to determine whether alcohol use and sexual risk behaviors were longitudinally related, examine the effects of the intervention on longitudinal alcohol use and sexual risk behaviors, identify latent subgroups of youths in the data for alcohol use and sexual risk behaviors, and determine whether the intervention influenced these subgroups. Results indicated alcohol use and sexual risk were longitudinally related. Subgroups of youth were also identified based on alcohol use and sexual risk behavior levels and trends. Further, limited treatment effects were observed for alcohol use. Implications of the results for future research and service delivery are considered. PMID:25242878

Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

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

Simontacchi, Gabriele; Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it; Ciammella, Patrizia

Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwentmore » blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage HL patients treated with combined modality therapy; the continuation of chemotherapy followed by radiation therapy is able to obtain durable, complete remission in most i-FDG-PET-positive patients.« less

The 1986/87 Army Communications Objectives Measurement System: Supplementary Tabulations of Enlisted Markets

DTIC Science & Technology

1988-07-01

and SEdward 11oke (We tat) 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month, Day) 15. PAGE COUNT Interim FROM 86/10 TO 87/06...TABULATIONS OF ENLISTED MARKETS 1. INTRODUCTION The Aray Communications Objectives Measurement System survey has been designed to provide timely information to...1987. During that time 6774 youth, ages 16 through 24, com- pleted the 30 minute ACOMS youth interview. A similar volume is also available for the

An Investigation of Factors Influencing Learning in the Mentally Retarded, and Their Use in the Design of Instructional Materials; Effects of a Set for Delayed Response on Recall by MR's. Interim Report.

ERIC Educational Resources Information Center

Seitz, Sue; Morris, Dan

In a study on short term memory, 32 educable mentally retarded subjects (mean IQ 62.68, mean mental age 103.78 months) were randomly assigned to each of the four experimental conditions. An automated machine presented the stimuli (32 three-letter words) and the interference items (a list of random numbers read aloud between stimuli presentations).…

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report.

PubMed

Grech, Victor; Grixti, Cynthia

2010-06-02

Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation.

76 FR 14559 - Federal Acquisition Regulation; Justification and Approval of Sole-Source 8(a) Contracts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... Space Administration (NASA). ACTION: Interim rule. SUMMARY: DoD, GSA, and NASA are issuing an interim..., and NASA are issuing an interim rule amending the FAR, to implement section 811 of the National... meetings, DoD, GSA, and NASA weighed the costs and benefits of publishing this rule as proposed or interim...

Interim Administrators in Higher Education: A National Study

ERIC Educational Resources Information Center

Huff, Marie Thielke; Neubrander, Judy

2015-01-01

The focus of this paper is on the roles and experiences of interim administrators in higher education. A survey was given to current and recent interim administrators in four-year public universities and colleges across the United States. The goals were to identify the advantages and disadvantages of using and serving as interims, and to solicit…

Interim Draft: Biological Sampling and Analysis Plan Outline ...

EPA Pesticide Factsheets

Standard Operation Procedures This interim sampling and analysis plan (SAP) outline was developed specifically as an outline of the output that will be generated by a developing on-line tool called the MicroSAP. The goal of the MicroSAP tool is to assist users with development of SAPs needed for site characterization, verification sampling, and post decontamination sampling stages of biological sampling and analysis activities in which the EPA would be responsible for conducting sampling. These activities could include sampling and analysis for a biological contamination incident, a research study, or an exercise. The development of this SAP outline did not consider the initial response of an incident, as it is assumed that the initial response would have been previously completed by another agency during the response, or the clearance phase, as it is assumed that separate committee would be established to make decisions regarding clearing a site. This outline also includes considerations for capturing the associated data quality objectives in the SAP.

Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial.

PubMed

Martins, Cesário L; Garly, May-Lill; Balé, Carlito; Rodrigues, Amabelia; Ravn, Henrik; Whittle, Hilton C; Lisse, Ida M; Aaby, Peter

2008-07-24

To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age. Randomised clinical trial. 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group. Urban area in Guinea-Bissau. Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age. Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age. 28% of the children tested at 4.5 months of age had protective levels of maternal antibodies against measles at enrolment. After early vaccination against measles 92% had measles antibodies at 9 months of age. A measles outbreak offered a unique situation for testing the efficacy of early measles vaccination. During the outbreak, 96 children developed measles; 19% of unvaccinated children had measles before 9 months of age. The monthly incidence of measles among the 441 children enrolled in the treatment arm was 0.7% and among the 892 enrolled in the control arm was 3.1%. Early vaccination with the Edmonston-Zagreb measles vaccine prevented infection; vaccine efficacy for children with serologically confirmed measles and definite clinical measles was 94% (95% confidence interval 77% to 99%), for admissions to hospital for measles was 100% (46% to 100%), and for measles mortality was 100% (-42% to 100%). The number needed to treat to prevent one case of measles between ages 4.5 months and 9 months during the epidemic was 7.2 (6.8 to 9.2). The treatment group tended to have lower overall mortality (mortality rate ratio 0.18, 0.02 to 1.36) although this was not significant. In low income countries, maternal antibody levels against measles may be low and severe outbreaks of measles can occur in infants before the recommended age of vaccination at 9 months. Outbreaks of measles may be curtailed by measles vaccination using the Edmonston-Zagreb vaccine as early as 4.5 months of age. TRIAL REGISTRATION CLINICAL TRIALS: NCT00168558 [ClinicalTrials.gov].

RESEARCH METHOD FOR SAMPLING AND ANALYSIS OF FIBROUS AMPHIBOLE IN VERMICULITE ATTIC INSULATION

EPA Science Inventory

NRMRL hosted a meeting on July 17-18, 2003 entitled, "Analytical Method for Bulk Analysis of Vermiculite." The purpose of this effort was to produce an interim research method for use by U.S. EPA's Office of Research and Development (ORD) for the analysis of bulk vermiculite for...

78 FR 8295 - Guarantees for Bonds Issued for Community or Economic Development Purposes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

.... V. Rulemaking Analysis A. Executive Order (E.O.) 12866; Regulatory Impact Analysis It has been... Budget. The Regulatory Impact Analysis prepared by the CDFI Fund for the interim rule is provided below... Community Investment Impact System (CIIS), which collects data from CDFIs that have received awards from the...

Adaptive graph-based multiple testing procedures

PubMed Central

Klinglmueller, Florian; Posch, Martin; Koenig, Franz

2016-01-01

Multiple testing procedures defined by directed, weighted graphs have recently been proposed as an intuitive visual tool for constructing multiple testing strategies that reflect the often complex contextual relations between hypotheses in clinical trials. Many well-known sequentially rejective tests, such as (parallel) gatekeeping tests or hierarchical testing procedures are special cases of the graph based tests. We generalize these graph-based multiple testing procedures to adaptive trial designs with an interim analysis. These designs permit mid-trial design modifications based on unblinded interim data as well as external information, while providing strong family wise error rate control. To maintain the familywise error rate, it is not required to prespecify the adaption rule in detail. Because the adaptive test does not require knowledge of the multivariate distribution of test statistics, it is applicable in a wide range of scenarios including trials with multiple treatment comparisons, endpoints or subgroups, or combinations thereof. Examples of adaptations are dropping of treatment arms, selection of subpopulations, and sample size reassessment. If, in the interim analysis, it is decided to continue the trial as planned, the adaptive test reduces to the originally planned multiple testing procedure. Only if adaptations are actually implemented, an adjusted test needs to be applied. The procedure is illustrated with a case study and its operating characteristics are investigated by simulations. PMID:25319733

Interim analyses in 2 x 2 crossover trials.

PubMed

Cook, R J

1995-09-01

A method is presented for performing interim analyses in long term 2 x 2 crossover trials with serial patient entry. The analyses are based on a linear statistic that combines data from individuals observed for one treatment period with data from individuals observed for both periods. The coefficients in this linear combination can be chosen quite arbitrarily, but we focus on variance-based weights to maximize power for tests regarding direct treatment effects. The type I error rate of this procedure is controlled by utilizing the joint distribution of the linear statistics over analysis stages. Methods for performing power and sample size calculations are indicated. A two-stage sequential design involving simultaneous patient entry and a single between-period interim analysis is considered in detail. The power and average number of measurements required for this design are compared to those of the usual crossover trial. The results indicate that, while there is minimal loss in power relative to the usual crossover design in the absence of differential carry-over effects, the proposed design can have substantially greater power when differential carry-over effects are present. The two-stage crossover design can also lead to more economical studies in terms of the expected number of measurements required, due to the potential for early stopping. Attention is directed toward normally distributed responses.

76 FR 15919 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition To List the Berry...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

...We, the U.S. Fish and Wildlife Service (Service), announce a 12-month finding on a petition to list the Berry Cave salamander (Gyrinophilus gulolineatus) as endangered under the Endangered Species Act of 1973, as amended (Act). After review of all available scientific and commercial information, we find that listing the Berry Cave salamander is warranted. Currently, however, listing is precluded by higher priority actions to amend the Lists of Endangered and Threatened Wildlife and Plants. Upon publication of this 12-month petition finding, we will add the Berry Cave salamander to our candidate species list. We will develop a proposed rule to list the Berry Cave salamander as our priorities allow. We will make any determination on critical habitat during development of the proposed listing rule. During any interim period, we will address the status of the candidate taxon through our annual Candidate Notice of Review (CNOR).

78 FR 49422 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition to List the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

...We, the U.S. Fish and Wildlife Service (Service), announce a 12-month finding on a petition to list the rattlesnake-master borer moth (Papaipema eryngii) as an endangered or a threatened species under the Endangered Species Act of 1973, as amended (Act). After review of the best available scientific and commercial information, we find that listing the rattlesnake-master borer moth is warranted. Currently, however, listing the rattlesnake-master borer moth is precluded by higher priority actions to amend the Lists of Endangered and Threatened Wildlife and Plants. Upon publication of this 12-month petition finding, we will add the rattlesnake-master borer moth to our candidate species list. We will develop a proposed rule to list the rattlesnake- master borer moth as our priorities allow. In any interim period, we will address the status of the candidate taxon through our annual Candidate Notice of Review (CNOR).

On the comparisons of tropical relative humidity in the lower and middle troposphere among COSMIC radio occultations and MERRA and ECMWF data sets

NASA Astrophysics Data System (ADS)

Vergados, P.; Mannucci, A. J.; Ao, C. O.; Jiang, J. H.; Su, H.

2015-04-01

The spatial variability of the tropical tropospheric relative humidity (RH) throughout the vertical extent of the troposphere is examined using Global Positioning System Radio Occultation (GPSRO) observations from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) mission. These high vertical resolution observations capture the detailed structure and moisture budget of the Hadley Cell circulation. We compare the COSMIC observations with the European Center for Medium-range Weather Forecast (ECMWF) Reanalysis Interim (ERA-Interim) and the Modern-Era Retrospective analysis for Research and Applications (MERRA) climatologies. Qualitatively, the spatial pattern of RH in all data sets matches up remarkably well, capturing distinct features of the general circulation. However, RH discrepancies exist between ERA-Interim and COSMIC data sets that are noticeable across the tropical boundary layer. Specifically, ERA-Interim shows a drier Intertropical Convergence Zone (ITCZ) by 15-20% compared to both COSMIC and MERRA data sets, but this difference decreases with altitude. Unlike ECMWF, MERRA shows an excellent agreement with the COSMIC observations except above 400 hPa, where GPSRO observations capture drier air by 5-10%. RH climatologies were also used to evaluate intraseasonal variability. The results indicate that the tropical middle troposphere at ±5-25° is most sensitive to seasonal variations. COSMIC and MERRA data sets capture the same magnitude of the seasonal variability, but ERA-Interim shows a weaker seasonal fluctuation up to 10% in the middle troposphere inside the dry air subsidence regions of the Hadley Cell. Over the ITCZ, RH varies by maximum 9% between winter and summer.

IVHS Countermeasures for Rear-End Collisions, Task 1 Vol. III: 1991 NASS CDS Case Analysis

DOT National Transportation Integrated Search

1994-02-15

This report is from the NHTSA sponsored program, "IVHS Countermeasures for Rear-End Collisions". The Task 1 Interim Report consists of six volumes. This Volume, Volume III, 1991 NASS CDS Clinical Case Analysis presents the results of a clinical case ...

42 CFR 418.307 - Periodic interim payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) MEDICARE PROGRAM HOSPICE CARE Payment for Hospice Care § 418.307 Periodic interim payments... payments. The biweekly interim payment amount is based on the total estimated Medicare payments for the...

Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

PubMed Central

Bhagat, Shaum P.; Bass, Johnnie K.; White, Stephanie T.; Qaddoumi, Ibrahim; Wilson, Matthew W.; Wu, Jianrong; Rodriguez-Galindo, Carlos

2016-01-01

Objective Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children. Methods A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f2= 793–7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3–4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels. Results Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f2=7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels. Conclusions Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3–4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity. PMID:20667604

[Response to US review rules on patent subject matter of traditional Chinese medicine compositions].

PubMed

Liu, Pan; Cao, Ya-di; Gong, Rui-Juan; Liu, Wei

2018-02-01

The United States Patent and Trademark Office(USPTO) issued Interim Guidance on Patent Subject Matter Eligibility on December 16， 2014， bringing certain effects to the review rules on patent application of Chinese medicine compositions. Based on the Interim Guidance， cases analysis was used in this paper to analyze the patent subject matter issues of traditional Chinese medicine compositions in the United States. The researches have shown that the application documents should be properly written in the United States when the patent for Chinese medicine compositions is applied， which can improve the probability of authorization. Copyright© by the Chinese Pharmaceutical Association.

Mobile source air toxics mitigation measures.

DOT National Transportation Integrated Search

2013-10-01

In accordance with the Federal Highway Administration (FHWA) Interim Guidance Update on Mobile Source Air Toxic Analysis in NEPA Documents (September 30, 2009), transportation projects subject to the National Environmental Policy Act (NEPA) mus...

Safe Passage Data Analysis: Interim Report

DOT National Transportation Integrated Search

1993-04-01

The purpose of this report is to describe quantitatively the costs and benefits of screener : proficiency evaluation and reporting systems (SPEARS) equipment, particularly computer-based : instruction (CBI) systems, compared to current methods of tra...

Analysis of the factors that impact the reliability of high level waste canister materials

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

Boyd, W.K.; Hall, A.M.

1977-09-19

The analysis encompassed identification and analysis of potential threats to canister integrity arising in the course of waste solidification, interim storage at the fuels reprocessing plant, wet and dry shipment, and geologic storage. Fabrication techniques and quality assurance requirements necessary to insure optimum canister reliability were considered taking into account such factors as welding procedure, surface preparation, stress relief, remote weld closure, and inspection methods. Alternative canister materials and canister systems were also considered in terms of optimum reliability in the face of threats to the canister's integrity, ease of fabrication, inspection, handling and cost. If interim storage in airmore » is admissible, the sequence suggested comprises producing a glass-type waste product in a continuous ceramic melter, pouring into a carbon steel or low-alloy steel canister of moderately heavy wall thickness, storing in air upright on a pad and surrounded by a concrete radiation shield, and thereafter placing in geologic storage without overpacking. Should the decision be to store in water during the interim period, then use of either a 304 L stainless steel canister overpacked with a solution-annealed and fast-cooled 304 L container, or a single high-alloy canister, is suggested. The high alloy may be Inconel 600, Incoloy Alloy 800, or Incoloy Alloy 825. In either case, it is suggested that the container be overpacked with a moderately heavy wall carbon steel or low-alloy steel cask for geologic storage to ensure ready retrievability. 19 figs., 5 tables.« less

Safety and efficacy of long-term treatment with teneligliptin: Interim analysis of a post-marketing surveillance of more than 10,000 Japanese patients with type 2 diabetes mellitus.

PubMed

Kadowaki, Takashi; Haneda, Masakazu; Ito, Hiroshi; Ueno, Makoto; Matsukawa, Miyuki; Yamakura, Tomoko; Sasaki, Kazuyo; Kimura, Mayumi; Iijima, Hiroaki

2018-02-01

This post-marketing surveillance examined the safety and efficacy of long-term teneligliptin therapy in Japanese patients. We report interim results (cut-off date: 28 June 2017) of a 3-year PMS undertaken in subjects with type 2 diabetes mellitus (T2DM). Survey items included demographics, treatments, adverse drug reactions (ADRs), and laboratory variables. A subgroup analysis was also performed across three age groups (<65 years; 65 to <75 years; ≥75 years). Main outcome measures were incidence of ADRs, laboratory variables, and change in glycated hemoglobin (HbA1c) from baseline over time. Of 11,677 patients registered, data from 10,532 patients (6,338 males/4,194 females) were analyzed for the safety analysis set; the median administration period was 731 days. Overall, ADRs and serious ADRs were reported in 364 (3.46%) and 91 patients (0.86%), respectively. The most common ADRs were all hypoglycemia (0.32%), constipation (0.27%), and hepatic function abnormal (0.24%). No change in mean body weight occurred, and a reduction in mean HbA1c was observed until 2 years. The safety and efficacy profiles did not differ markedly among the three age groups. These interim results show that teneligliptin was well tolerated and improved hyperglycemia in Japanese patients with T2DM in clinical practice.

Near-surface wind speed statistical distribution: comparison between ECMWF System 4 and ERA-Interim

NASA Astrophysics Data System (ADS)

Marcos, Raül; Gonzalez-Reviriego, Nube; Torralba, Verónica; Cortesi, Nicola; Young, Doo; Doblas-Reyes, Francisco J.

2017-04-01

In the framework of seasonal forecast verification, knowing whether the characteristics of the climatological wind speed distribution, simulated by the forecasting systems, are similar to the observed ones is essential to guide the subsequent process of bias adjustment. To bring some light about this topic, this work assesses the properties of the statistical distributions of 10m wind speed from both ERA-Interim reanalysis and seasonal forecasts of ECMWF system 4. The 10m wind speed distribution has been characterized in terms of the four main moments of the probability distribution (mean, standard deviation, skewness and kurtosis) together with the coefficient of variation and goodness of fit Shapiro-Wilks test, allowing the identification of regions with higher wind variability and non-Gaussian behaviour at monthly time-scales. Also, the comparison of the predicted and observed 10m wind speed distributions has been measured considering both inter-annual and intra-seasonal variability. Such a comparison is important in both climate research and climate services communities because it provides useful climate information for decision-making processes and wind industry applications.

Impact of quality management monitoring and intervention on central venous catheter dysfunction in the outpatient chemotherapy infusion setting.

PubMed

Bansal, Anu; Binkert, Christoph A; Robinson, Malcolm K; Shulman, Lawrence N; Pellerin, Linda; Davison, Brian

2008-08-01

To assess the utility of maintaining and analyzing a quality-management database while investigating a subjectively perceived increase in the incidence of tunneled catheter and port dysfunction in a cohort of oncology outpatients. All 152 patients undergoing lytic therapy (2-4 mg alteplase) of a malfunctioning indwelling central venous catheter (CVC) from January through June 2004 at a single cancer center in the United States were included in a quality-management database. Patients were categorized by time to device failure and the initial method of catheter placement (surgery vs interventional radiology). Data were analyzed after 3 months, and areas of possible improvement were identified and acted upon. Three months of follow-up data were then collected and similarly analyzed. In a 6-month period, 152 patients treated for catheter malfunction received a total of 276 doses of lytic therapy. A 3-month interim analysis revealed a disproportionately high rate (34%) of early catheter malfunction (ECM; <30 days from placement). Postplacement radiographs demonstrated suboptimal catheter positioning in 67% of these patients, all of whom had surgical catheter placement. There was a 50% absolute decrease in the number of patients presenting with catheter malfunction in the period from April through June (P < .001). Evaluation of postplacement radiographs in these patients demonstrated a 50% decrease in the incidence of suboptimal positioning (P < .05). Suboptimal positioning was likely responsible for some, but not all, cases of ECM. Maintenance of a quality-management database is a relatively simple intervention that can have a clear and important impact on the quality and cost of patient care.

FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma

PubMed Central

Prowell, Tatiana M.; Ibrahim, Amna; Farrell, Ann T.; Justice, Robert; Mitchell, Shan Sun; Sridhara, Rajeshwari; Pazdur, Richard

2010-01-01

This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel®), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-α versus those receiving temsirolimus alone or in combination with IFN-α. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-α arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-α did not lead to a significant difference in OS compared with IFN-α alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-α arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-α and provides an additional treatment option for patients with advanced RCC. PMID:20332142

Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study.

PubMed

Ashina, Messoud; Dodick, David; Goadsby, Peter J; Reuter, Uwe; Silberstein, Stephen; Zhang, Feng; Gage, Julia R; Cheng, Sunfa; Mikol, Daniel D; Lenz, Robert A

2017-09-19

To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM). Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data. Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28-822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo. One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM. NCT01952574. This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life. © 2017 American Academy of Neurology.

A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial.

PubMed

Davidson, A; Veillard, A-S; Tognela, A; Chan, M M K; Hughes, B G M; Boyer, M; Briscoe, K; Begbie, S; Abdi, E; Crombie, C; Long, J; Boyce, A; Lewis, C R; Varma, S; Broad, A; Muljadi, N; Chinchen, S; Espinoza, D; Coskinas, X; Pavlakis, N; Millward, M; Stockler, M R

2015-11-01

We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392. © The Author 2015. 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.

Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

PubMed

Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

2013-02-10

In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection.

PubMed

Dubberke, Erik R; Mullane, Kathleen M; Gerding, Dale N; Lee, Christine H; Louie, Thomas J; Guthertz, Harriet; Jones, Courtney

2016-09-01

Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods.  A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results.  VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions.  Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

PubMed

Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

2013-10-01

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials. The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

Replacement of a hopeless maxillary central incisor: a technique for the fabrication of an immediate implant-supported interim restoration.

PubMed

Graiff, Lorenzo; Vigolo, Paolo

2012-04-01

Placement of a dental implant and an interim restoration in the esthetic zone immediately following tooth extraction is now a common procedure. However, in such clinical situations, the fabrication of an appropriate interim restoration may be challenging. The aim of this article is to present a technique for modifying the extracted tooth so it can be used as an implant-supported interim restoration.

REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia

PubMed Central

Boyd, Roslyn N; Ziviani, Jenny; Sakzewski, Leanne; Novak, Iona; Badawi, Nadia; Pannek, Kerstin; Elliott, Catherine; Greaves, Susan; Guzzetta, Andrea; Whittingham, Koa; Valentine, Jane; Morgan, Cathy; Wallen, Margaret; Eliasson, Ann-Christin; Findlay, Lisa; Ware, Robert; Fiori, Simona; Rose, Stephen

2017-01-01

Objectives Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. Methods and analysis 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. Ethics and dissemination Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. Trial registration number Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results. PMID:28928195

Interim analysis of STR effectiveness

DOT National Transportation Integrated Search

1978-01-01

The present report describes the status of the NHTSA Short Term Rehabilitation Study (STR) as of December, 1977, and summarizes the progress of data collection efforts by the eleven participating ASAP projects. Outcome measures considered as indicati...

Palbociclib for Advanced Breast Cancer

Cancer.gov

An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

ZWD time series analysis derived from NRT data processing. A regional study of PW in Greece.

NASA Astrophysics Data System (ADS)

Pikridas, Christos; Balidakis, Kyriakos; Katsougiannopoulos, Symeon

2015-04-01

ZWD (Zenith Wet/non-hydrostatic Delay) estimates are routinely derived Near Real Time from the new established Analysis Center in the Department of Geodesy and Surveying of Aristotle University of Thessaloniki (DGS/AUT-AC), in the framework of E-GVAP (EUMETNET GNSS water vapour project) since October 2014. This process takes place on an hourly basis and yields, among else, station coordinates and tropospheric parameter estimates for a network of 90+ permanent GNSS (Global Navigation Satellite System) stations. These are distributed at the wider part of Hellenic region. In this study, temporal and spatial variability of ZWD estimates were examined, as well as their relation with coordinate series extracted from both float and fixed solution of the initial phase ambiguities. For this investigation, Bernese GNSS Software v5.2 was used for the acquisition of the 6 month dataset from the aforementioned network. For time series analysis we employed techniques such as the Generalized Lomb-Scargle periodogram and Burg's maximum entropy method due to inefficiencies of the Discrete Fourier Transform application in the test dataset. Through the analysis, interesting results for further geophysical interpretation were drawn. In addition, the spatial and temporal distributions of Precipitable Water vapour (PW) obtained from both ZWD estimates and ERA-Interim reanalysis grids were investigated.

Global Trends and Variability in Integrated Water Vapor from Ground-Based GPS Data and Climate Models

NASA Astrophysics Data System (ADS)

Bock, O.; Parracho, A. C.; Bastin, S.; Hourdin, F.

2016-12-01

A high-quality, consistent, global, long-term dataset of integrated water vapor (IWV) was produced from Global Positioning System (GPS) measurements at more than 400 sites over the globe among which 120 sites have more than 15 years of data. The GPS delay data were converted to IWV using surface pressure and weighted mean temperature estimates from ERA-Interim reanalysis. A two-step screening method was developed to detect and remove outliers in the IWV data. It is based on: 1) GPS data processing information and delay formal errors, and 2) inter-comparison with ERA-Interim reanalysis data. The GPS IWV data are also homogenized to correct for offsets due to instrumental changes and other unknown factors. The differential homogenization method uses ERA-Interim IWV as a reference. The resulting GPS data are used to document the mean distribution, the global trends and the variability of IWV over the period 1995-2010, and to assess global climate model simulations extracted from the IPCC AR5 archive. Large coherent spatial patterns of moistening and drying are evidenced but significant discrepancies are also seen between GPS measurements, reanalysis and climate models in various regions. In terms of variability, the monthly mean anomalies are inter-compared. The temporal correlation between GPS and the climate model simulations is overall quite small but the spatial variation of the magnitude of the anomalies is globally well simulated. GPS IWV data prove to be useful to validate global climate model simulations and highlight deficiencies in their representation of the water cycle.

Comparison of trends and abrupt changes of the South Asia high from 1979 to 2014 in reanalysis and radiosonde datasets

NASA Astrophysics Data System (ADS)

Shi, Chunhua; Huang, Ying; Guo, Dong; Zhou, Shunwu; Hu, Kaixi; Liu, Yu

2018-05-01

The South Asian High (SAH) has an important influence on atmospheric circulation and the Asian climate in summer. However, current comparative analyses of the SAH are mostly between reanalysis datasets and there is a lack of sounding data. We therefore compared the climatology, trends and abrupt changes in the SAH in the Japanese 55-year Reanalysis (JRA-55) dataset, the National Centers for Environmental Prediction Climate Forecast System Reanalysis (NCEP-CFSR) dataset, the European Center for Medium-Range Weather Forecasts Reanalysis Interim (ERA-interim) dataset and radiosonde data from China using linear analysis and a sliding t-test. The trends in geopotential height in the control area of the SAH were positive in the JRA-55, NCEP-CFSR and ERA-interim datasets, but negative in the radiosonde data in the time period 1979-2014. The negative trends for the SAH were significant at the 90% confidence level in the radiosonde data from May to September. The positive trends in the NCEP-CFSR dataset were significant at the 90% confidence level in May, July, August and September, but the positive trends in the JRA-55 and ERA-Interim were only significant at the 90% confidence level in September. The reasons for the differences in the trends of the SAH between the radiosonde data and the three reanalysis datasets in the time period 1979-2014 were updates to the sounding systems, changes in instrumentation and improvements in the radiation correction method for calculations around the year 2000. We therefore analyzed the trends in the two time periods of 1979-2000 and 2001-2014 separately. From 1979 to 2000, the negative SAH trends in the radiosonde data mainly agreed with the negative trends in the NCEP-CFSR dataset, but were in contrast with the positive trends in the JRA-55 and ERA-Interim datasets. In 2001-2014, however, the trends in the SAH were positive in all four datasets and most of the trends in the radiosonde and NCEP-CFSR datasets were significant. It is therefore better to use the NCEP-CFSR dataset than the JRA-55 and ERA-Interim datasets when discussing trends in the SAH.

International validation study for interim PET in ABVD-treated, advanced-stage hodgkin lymphoma: interpretation criteria and concordance rate among reviewers.

PubMed

Biggi, Alberto; Gallamini, Andrea; Chauvie, Stephane; Hutchings, Martin; Kostakoglu, Lale; Gregianin, Michele; Meignan, Michel; Malkowski, Bogdan; Hofman, Michael S; Barrington, Sally F

2013-05-01

At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α. The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.

Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report

PubMed Central

2010-01-01

Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186

COBRA System Engineering Processes to Achieve SLI Strategic Goals

NASA Technical Reports Server (NTRS)

Ballard, Richard O.

2003-01-01

The COBRA Prototype Main Engine Development Project was an endeavor conducted as a joint venture between Pratt & Whitney and Aerojet to conduct risk reduction in LOX/LH2 main engine technology for the NASA Space Launch Initiative (SLI). During the seventeen months of the project (April 2001 to September 2002), approximately seventy reviews were conducted, beginning with the Engine Systems Requirements Review (SRR) and ending with the Engine Systems Interim Design Review (IDR). This paper discusses some of the system engineering practices used to support the reviews and the overall engine development effort.

Guidance: Interim Municipal Settlement Policy

EPA Pesticide Factsheets

Interim guidance and fact sheets regarding settlements involving municipalities or municipal waste under Section 122 CERCLA as amended by SARA. Interim policy sets forth the criteria by which EPA generally determines whether to exercise enforcement discretion to pursue MSW generators and transporters as PRPs.

Photomorphic analysis techniques: An interim spatial analysis using satellite remote sensor imagery and historical data

NASA Technical Reports Server (NTRS)

Keuper, H. R.; Peplies, R. W.; Gillooly, R. P.

1977-01-01

The use of machine scanning and/or computer-based techniques to provide greater objectivity in the photomorphic approach was investigated. Photomorphic analysis and its application in regional planning are discussed. Topics included: delineation of photomorphic regions; inadequacies of existing classification systems; tonal and textural characteristics and signature analysis techniques; pattern recognition and Fourier transform analysis; and optical experiments. A bibliography is included.

Science Opportunities Enabled by NASA's Constellation System: Interim Report

NASA Astrophysics Data System (ADS)

Committee On Science Opportunities Enabled By Nasa'S Constellation System, National Research Council

To begin implementation of the Vision for Space Exploration (recently renamed "United States Space Exploration Policy"), NASA has begun development of new launch vehicles and a human-carrying spacecraft that are collectively called the Constellation System. In November 2007, NASA asked the NRC to evaluate the potential for the Constellation System to enable new space science opportunities. For this interim report, 11 existing "Vision Mission" studies of advanced space science mission concepts inspired by earlier NASA forward-looking studies were evaluated. The focus was to assess the concepts and group them into two categories: more-deserving or less deserving of future study. This report presents a description of the Constellation System and its opportunities for enabling new space science opportunities, and a systematic analysis of the 11 Vision Mission studies. For the final report, the NRC issued a request for information to the relevant communities to obtain ideas for other mission concepts that will be assessed by the study committee, and several issues addressed only briefly in the interim report will be explored more fully.

NAVSTAR GPS Simulation and Analysis Program (Interim Report)

DOT National Transportation Integrated Search

1983-10-01

This study assesses the capability of the planned NAVSTAR Global Positioning System (GPS) to meet civil navigation requirements. When it becomes operational in about 1983, NAVSTAR GPS will provide accurate two-dimensional and three-dimensional servic...

75 FR 65349 - Decision To Evaluate a Petition To Designate a Class of Employees From BWX Technologies Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

...: Lynchburg, Virginia. Job Titles and/or Job Duties: All Atomic Weapons Employer employees. Period of..., Interim Director, Division of Compensation Analysis and Support, National Institute for Occupational...

75 FR 4822 - Decision To Evaluate a Petition To Designate a Class of Employees for the Lawrence Livermore...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...: Lawrence Livermore National Laboratory. Location: Livermore, California. Job Titles and/or Job Duties: All... L. Hinnefeld, Interim Director, Office of Compensation Analysis and Support, National Institute for...

Road weather connected vehicle applications : benefit-cost analysis interim report.

DOT National Transportation Integrated Search

2013-01-01

RWMP is currently engaged in a project to evaluate the potential benefits of road weather connected vehicle applications. Of particular interest are the potential improvements in safety, reductions in travel time, improved travel reliability, reducti...

Benefit-Risk Summary of Nivolumab for Patients With Metastatic Squamous Cell Lung Cancer After Platinum-Based Chemotherapy: A Report From the US Food and Drug Administration.

PubMed

Kazandjian, Dickran; Khozin, Sean; Blumenthal, Gideon; Zhang, Lijun; Tang, Shenghui; Libeg, Meredith; Kluetz, Paul; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

2016-01-01

Metastatic squamous non-small-cell lung cancer (SQ NSCLC) is a serious and life-threatening malignant condition with unmet medical need. In late December 2014, the US Food and Drug Administration (FDA) obtained the data monitoring committee report of a planned interim analysis of a trial in second-line SQ NSCLC (CM017) that demonstrated an overall survival benefit for patients treated with nivolumab compared with docetaxel. In that trial, 272 patients with metastatic SQ NSCLC patients had been randomized to receive nivolumab (n = 135) or docetaxel (n = 137). Median overall survival was 9.2 months for patients randomized to nivolumab and 6.0 months for those randomized to docetaxel (hazard ratio, 0.59; 95% CI, 0.44-0.79; P < .001). The safety of nivolumab was evaluated in a single-arm trial of 117 patients in previously treated metastatic SQ NSCLC and was consistent with the safety profile in melanoma, with rare but serious immune-mediated adverse events managed with corticosteroids and dose interruption. The FDA granted nivolumab traditional approval on March 4, 2015, for treatment of metastatic SQ NSCLC with progression during or after platinum-based chemotherapy. The approval provides an important treatment option for these patients, affecting routine care and clinical trials.

Postabortion contraception a decade after legalization of abortion in Nepal.

PubMed

Rocca, Corinne H; Puri, Mahesh; Harper, Cynthia C; Blum, Maya; Dulal, Bishnu; Henderson, Jillian T

2014-08-01

To assess the contraceptive information received and methods chosen, received, and used among women having abortions one decade after legalization of abortion in Nepal. We examined postabortion contraception with questionnaires at baseline and six months among women obtaining legal abortions (n=838) at four facilities in 2011. Multivariate regression analysis was used to measure factors associated with method information, choice, receipt, and use. One-third of participants received no information on effective methods, and 56% left facilities without a method. The majority of women who chose to use injectables and pills were able to do so (88% and 75%, respectively). However, only 44% of women choosing long-acting reversible contraceptives and 5% choosing sterilization had initiated use of the method by six months. Levels of contraceptive use after medical abortion were on par with those after aspiration abortion. Nulliparous women were far less likely than parous women to receive information and use methods. Women living without husbands or partners were also less likely to receive information and supplies, or to use methods. Improvements in postabortion counseling and provision are needed. Ensuring that women choosing long-acting and permanent contraceptive methods are able to obtain either them or interim methods is essential. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Changes in the zonal mean flow, temperature, and planetary waves observed in the Northern Hemisphere mid-winter months during the last decades

NASA Astrophysics Data System (ADS)

Rakushina, E. V.; Ermakova, T. S.; Pogoreltsev, A. I.

2018-06-01

Four sets of data: the UK Met Office, Modern Era Retrospective-analysis for Research and Applications (MERRA), Japanese 55-year Reanalysis data (JRA-55), and ERA-Interim data (ERA) have been used to estimate the climatic variability of the zonal mean flow, temperature, and Stationary Planetary Waves (SPW1, SPW2) from the troposphere up to the lower mesosphere levels. The composites of the meteorological fields during mid-winter month have been averaged over the first (1995-2005) and second (2006-2016) 11 years intervals and have been compared mainly paying attention to interannual and intraseasonal variability. Results show that changes in the mean fields and SPW2 are weaker and statistical significance of these changes is lower in comparison with the changes observed in the intraseasonal variability of these characteristics. All data sets demonstrate a decrease of SPW1 amplitude at the higher-middle latitudes in the lower stratosphere and opposite effect in the upper stratosphere. However, there is an increase of the intraseasonal variability for all meteorological parameters and this rise is statistically significant. The results obtained show that UK Met Office data demonstrate stronger changes and increase of the intraseasonal variability in comparison with other data sets.

INTERIM ANALYSIS OF THE CONTRIBUTION OF HIGH-LEVEL EVIDENCE FOR DENGUE VECTOR CONTROL.

PubMed

Horstick, Olaf; Ranzinger, Silvia Runge

2015-01-01

This interim analysis reviews the available systematic literature for dengue vector control on three levels: 1) single and combined vector control methods, with existing work on peridomestic space spraying and on Bacillus thuringiensis israelensis; further work is available soon on the use of Temephos, Copepods and larvivorous fish; 2) or for a specific purpose, like outbreak control, and 3) on a strategic level, as for example decentralization vs centralization, with a systematic review on vector control organization. Clear best practice guidelines for methodology of entomological studies are needed. There is a need to include measuring dengue transmission data. The following recommendations emerge: Although vector control can be effective, implementation remains an issue; Single interventions are probably not useful; Combinations of interventions have mixed results; Careful implementation of vector control measures may be most important; Outbreak interventions are often applied with questionable effectiveness.

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

28 CFR 94.41 - Interim emergency payment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Interim emergency payment. 94.41 Section 94.41 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CRIME VICTIM SERVICES International Terrorism Victim Expense Reimbursement Program Payment of Claims § 94.41 Interim emergency payment...

76 FR 4369 - Special Law Enforcement Commissions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Special Law Enforcement Commissions AGENCY... of the Interim Special Law Enforcement Commission Policy, Rules and Procedures, the Interim Special Law Enforcement Commission Protocols and the Interim Domestic Violence Waiver that will be used by the...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Interim transport and termination pricing. 51... SERVICES (CONTINUED) INTERCONNECTION Reciprocal Compensation for Transport and Termination of Telecommunications Traffic § 51.715 Interim transport and termination pricing. (a) Upon request from a...

47 CFR 51.715 - Interim transport and termination pricing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Interim transport and termination pricing. 51... SERVICES (CONTINUED) INTERCONNECTION Reciprocal Compensation for Transport and Termination of Telecommunications Traffic § 51.715 Interim transport and termination pricing. (a) Upon request from a...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2014 CFR

2014-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

33 CFR 385.9 - Implementation principles.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of the Plan at specific time intervals during implementation. Interim targets to evaluate progress on... accordance with § 385.39. Interim goals and interim targets shall be consistent with each other. (c... ensure that new information resulting from changed or unforeseen circumstances, new scientific and...

Investigation of Kelvin wave periods during Hai-Tang typhoon using Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Kishore, P.; Jayalakshmi, J.; Lin, Pay-Liam; Velicogna, Isabella; Sutterley, Tyler C.; Ciracì, Enrico; Mohajerani, Yara; Kumar, S. Balaji

2017-11-01

Equatorial Kelvin waves (KWs) are fundamental components of the tropical climate system. In this study, we investigate Kelvin waves (KWs) during the Hai-Tang typhoon of 2005 using Empirical Mode Decomposition (EMD) of regional precipitation, zonal and meridional winds. For the analysis, we use daily precipitation datasets from the Global Precipitation Climatology Project (GPCP) and wind datasets from the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-analysis (ERA-Interim). As an additional measurement, we use in-situ precipitation datasets from rain-gauges over the Taiwan region. The maximum accumulated precipitation was approximately 2400 mm during the period July 17-21, 2005 over the southwestern region of Taiwan. The spectral analysis using the wind speed at 950 hPa found in the 2nd, 3rd, and 4th intrinsic mode functions (IMFs) reveals prevailing Kelvin wave periods of ∼3 days, ∼4-6 days, and ∼6-10 days, respectively. From our analysis of precipitation datasets, we found the Kelvin waves oscillated with periods between ∼8 and 20 days.

Modeling surface response of the Greenland Ice Sheet to interglacial climate

NASA Astrophysics Data System (ADS)

Rau, Dominik; Rogozhina, Irina

2013-04-01

We present a new parameterization of surface mass balance (SMB) of the Greenland Ice Sheet (GIS) under interglacial climate conditions validated against recent satellite observations on a regional scale. Based on detailed analysis of the modeled surface melting and refreezing rates, we conclude that the existing SMB parameterizations fail to capture either spatial pattern or amplitude of the observed surface response of the GIS. This is due to multiple simplifying assumptions adopted by the majority of modeling studies within the frame of the positive degree day method. Modeled spatial distribution of surface melting is found to be highly sensitive to a choice of daily temperature standard deviation (SD) and degree-day factors, which are generally assumed to have uniform distribution across the entire Greenland region. However, the use of uniform SD distribution and the range of commonly used SD values are absolutely unsupported by the ERA-40 and ERA-Interim climate data. In this region, SD distribution is highly inhomogeneous and characterized by low amplitudes during the summer months in the areas where most surface ice melting occurs. In addition, the use of identical degree day factors on both the eastern and western slopes of the GIS results in overestimation of surface runoff along the western coast of Greenland and significant underestimation along its eastern coast. Our approach is to make use of (i) spatially and seasonally variable SDs derived from ERA-40 and ERA-Interim time series, and (ii) spatially variable degree-day factors, measured across Greenland, Arctic Canada, Norway, Spitsbergen and Iceland. We demonstrate that the new approach is extremely efficient for modeling the evolution of the GIS during the observational period and the entire Holocene interglacial.

Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: A phase 3, randomized controlled trial.

PubMed

Mahableshwarkar, Atul R; Calabrese, Joseph R; Macek, Thomas A; Budur, Kumar; Adefuye, Adedeji; Dong, Xinxin; Hanson, Elizabeth; Sachs, Gary S

2017-10-15

The optimal long-term management strategy for bipolar I disorder patients is not yet established. Evidence supports the rationale for circadian rhythm regulation to prevent mood episode relapse in bipolar patients. This study evaluated the efficacy and safety of a new sublingual formulation of the melatonin receptor agonist ramelteon (ramelteon SL) as adjunctive therapy in the maintenance treatment of bipolar I patients. In a double-blinded trial in the United States and Latin America, adult bipolar I disorder patients stable for ≥ 8 weeks before baseline and with a mood episode 8 weeks to 9 months before screening, were randomized to once-daily ramelteon SL 0.1mg (n = 164), 0.4mg (n = 160), or 0.8mg (n = 154), or placebo (n = 164), in addition to their existing treatment. The primary endpoint was time from randomization to relapse of symptoms. The prespecified futility criterion in a planned, unblinded, independent interim analysis was the failure of all ramelteon SL doses to achieve a conditional power ≥ 30% compared with placebo. No significant differences between any dose of ramelteon SL and placebo were observed. The study was terminated after meeting the futility criteria. Ramelteon SL was well tolerated, with a safety profile consistent with that for oral ramelteon. A low rate of relapse events precluded detection of any statistically significant difference between groups. The study failed to demonstrate the efficacy of ramelteon SL as adjunctive maintenance therapy for bipolar disorder. Interim analyses for futility in clinical studies are valuable in preventing unnecessary exposure of subjects to interventions. Copyright © 2017. Published by Elsevier B.V.

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.

PubMed

Santos, Raul D; Duell, P Barton; East, Cara; Guyton, John R; Moriarty, Patrick M; Chin, Wai; Mittleman, Robert S

2015-03-01

To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. CLINICALTRIALS.GOV: NCT00694109. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

PubMed Central

Santos, Raul D.; Duell, P. Barton; East, Cara; Guyton, John R.; Moriarty, Patrick M.; Chin, Wai; Mittleman, Robert S.

2015-01-01

Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were −28, −27, −27, and −28%; and in apolipoprotein B −29, −28, −30, and −31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. Clinicaltrials.gov NCT00694109. PMID:24366918

78 FR 55339 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

...The Federal Deposit Insurance Corporation (FDIC) is adopting an interim final rule that revises its risk-based and leverage capital requirements for FDIC-supervised institutions. This interim final rule is substantially identical to a joint final rule issued by the Office of the Comptroller of the Currency (OCC) and the Board of Governors of the Federal Reserve System (Federal Reserve) (together, with the FDIC, the agencies). The interim final rule consolidates three separate notices of proposed rulemaking that the agencies jointly published in the Federal Register on August 30, 2012, with selected changes. The interim final rule implements a revised definition of regulatory capital, a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for FDIC-supervised institutions subject to the advanced approaches risk-based capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator. The interim final rule incorporates these new requirements into the FDIC's prompt corrective action (PCA) framework. In addition, the interim final rule establishes limits on FDIC-supervised institutions' capital distributions and certain discretionary bonus payments if the FDIC-supervised institution does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk-based capital requirements. The interim final rule amends the methodologies for determining risk-weighted assets for all FDIC-supervised institutions. The interim final rule also adopts changes to the FDIC's regulatory capital requirements that meet the requirements of section 171 and section 939A of the Dodd-Frank Wall Street Reform and Consumer Protection Act. The interim final rule also codifies the FDIC's regulatory capital rules, which have previously resided in various appendices to their respective regulations, into a harmonized integrated regulatory framework. In addition, the FDIC is amending the market risk capital rule (market risk rule) to apply to state savings associations. The FDIC is issuing these revisions to its capital regulations as an interim final rule. The FDIC invites comments on the interaction of this rule with other proposed leverage ratio requirements applicable to large, systemically important banking organizations. This interim final rule otherwise contains regulatory text that is identical to the common rule text adopted as a final rule by the Federal Reserve and the OCC. This interim final rule enables the FDIC to proceed on a unified, expedited basis with the other federal banking agencies pending consideration of other issues. Specifically, the FDIC intends to evaluate this interim final rule in the context of the proposed well- capitalized and buffer levels of the supplementary leverage ratio applicable to large, systemically important banking organizations, as described in a separate Notice of Proposed Rulemaking (NPR) published in the Federal Register August 20, 2013. The FDIC is seeking commenters' views on the interaction of this interim final rule with the proposed rule regarding the supplementary leverage ratio for large, systemically important banking organizations.

Impacts of carpool utilization on the Katy Freeway Transitway 42-month after evaluation. Interim report, September 1984-September 1989

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

Hawkins, H.G.; Christiansen, D.L.

1989-09-01

A major commitment has been made in the Houston area to develop physically separated transitways in the medians of freeways. The lanes are reserved for high-occupancy vehicles. Phase 1 of the first completed transitway opened on the Katy Freeway (I-10) in October 1984. The research study, funded jointly by the Metropolitan Transit Authority of Harris County and the Texas State Department of Highways and Public Transportation, was initiated in order to conduct a comprehensive analysis of the effects of permitting carpools to utilize the transitway. The report documents data collected in October 1988, 3.5 years after carpool utilization of themore » transitway began. The report compares the 1988 data to similar data collected before carpool utilization was permitted (March 1985) and after carpool utilization was permitted (April 1986, October 1987). These comparisons address numerous concerns and provide an indication of the effectiveness of allowing carpools on the transitway.« less

Impacts of carpool utilization on the Katy Freeway transitway 30-month after evaluation. Interim report, September 1984-April 1988

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

Christiansen, D.L.; McCasland, W.R.

1988-09-01

A major commitment has been made in the Houston area to develop physically separated transitways in the medians of freeways. The lanes are reserved for high-occupancy vehicles. Phase I of the first completed transitway opened on the Katy Freeway (I-10) in October 1984. Phase 2 opened in June 1987. To increase potential utilization of the facility, carpools began using the transitway on a test basis in April 1985. The research study, funded jointly by the Metropolitan Transit Authority of Harris County and the Texas State Department of Highways and Public Transportation, was initiated to undertake a comprehensive analysis of themore » effects of permitting carpool utilization. The report documents the data collected in October 1987, 2.5 years after carpool utilization of the transitway was permitted. In the report, these data are compared to similar data collected both before carpool utilization was permitted and on several occasions after carpool utilization was permitted.« less

Assessment of wave energy potential along the south coast of Java Island

NASA Astrophysics Data System (ADS)

Song, Qingyang; Mayerle, Roberto

2018-04-01

The south coast of Java Island has a great potential for wave energy. A long-term analysis of a 10-year wave dataset obtained from the ERA-Interim database is performed for preliminary wave energy assessment in this area, and it was seen that the annual median power is expected to exceed 20kW/m along the coast. A coastal wave model with an unstructured grid was run to reveal the wave conditions and to assess the wave energy potential along the coast in detail. The effect of swells and local wind on the wave conditions is investigated. Annual median wave power, water depth and distance from the coast are selected as criteria for the identification of suitable locations for wave energy conversion. Two zones within the study area emerge to be suitable for wave energy extraction. Swells from the southwest turned out to be the major source of wave energy and highest monthly median wave power reached about 33kW/m.

Antireflux Versus Conventional Plastic Stent in Malignant Biliary Obstruction: A Prospective Randomized Study.

PubMed

Vihervaara, Hanna; Grönroos, Juha M; Hurme, Saija; Gullichsen, Risto; Salminen, Paulina

2017-01-01

Endoscopic stents are used to relieve obstructive jaundice. The purpose of this prospective randomized study was to compare the patency of antireflux and conventional plastic biliary stent in relieving distal malignant biliary obstruction. All jaundiced patients admitted to hospital with suspected unresectable malignant distal biliary stricture between October 2009 and September 2010 were evaluated for the study. Eligible patients were randomized either to antireflux or conventional plastic stent arms. The primary endpoint was stent patency and the follow-up was continued either until the stent was occluded or until 6 months after the stent placement. At an interim analysis, antireflux stents (ARSs; n = 6) had a significantly shorter median patency of 34 (8-49) days compared with the conventional stent (n = 7) patency of 167 (38-214) days (P = .0003). Based on these results, the study was terminated due to ethical concerns. According to these results, the use of this ARS is not recommended.

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study.

PubMed

Skinner, S Rachel; Szarewski, Anne; Romanowski, Barbara; Garland, Suzanne M; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Del Rosario-Raymundo, M Rowena; Verheijen, René H M; Quek, Swee Chong; da Silva, Daniel P; Kitchener, Henry; Fong, Kah Leng; Bouchard, Céline; Money, Deborah M; Ilancheran, Arunachalam; Cruickshank, Margaret E; Levin, Myron J; Chatterjee, Archana; Stapleton, Jack T; Martens, Mark; Quint, Wim; David, Marie-Pierre; Meric, Dorothée; Hardt, Karin; Descamps, Dominique; Geeraerts, Brecht; Struyf, Frank; Dubin, Gary

2014-12-20

Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women. In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26-35 and 36-45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40·3 months. This study is registered with ClinicalTrials.gov, number NCT00294047. The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81·1%, 97·7% CI 52·1-94·0), in the 26-35 years age group (83·5%, 45·0-96·8), and in the 36-45 years age group (77·2%, 2·8-96·9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79·1%, 97·7% CI 27·6-95·9) and HPV 45 (76·9%, 18·5-95·6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination. In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45. GlaxoSmithKline Biologicals SA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

42 CFR 417.574 - Interim settlement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Interim settlement. 417.574 Section 417.574 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... PLANS Medicare Payment: Cost Basis § 417.574 Interim settlement. (a) Determination. Within 30 days...

14 CFR 136.41 - Interim operating authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Interim operating authority. 136.41 Section 136.41 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... technology, as appropriate, and (9) Shall allow for modifications of the interim operating authority based on...

14 CFR 136.41 - Interim operating authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Interim operating authority. 136.41 Section 136.41 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... technology, as appropriate, and (9) Shall allow for modifications of the interim operating authority based on...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Interim hybrid IBOC DAB operation. 73.404 Section 73.404 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The...

10 CFR 590.403 - Emergency interim orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Opinions and Orders § 590.403 Emergency interim... and issue an emergency interim order authorizing the import or export of natural gas. After issuance...

EPA Interim Evaluation of 2016-2017 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2016-2017 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2016-2017 milestones, recognizing the achievements made in 2016.

EPA Interim Evaluation of 2012-2013 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2012-2013 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2012-2013 milestones, recognizing the achievements made in 2012.

49 CFR 37.193 - Interim service requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Interim service requirements. 37.193 Section 37.193 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.193 Interim service requirements. (a) Until...

76 FR 57657 - Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

...] Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This regulation establishes an extension of time-limited interim..., and Cosmetic Act (FFDCA). The time-limited tolerances expire on March 18, 2013. DATES: This regulation...

EPA Interim Evaluation of 2014-2015 Milestone Progress in the Chesapeake Bay Watershed

EPA Pesticide Factsheets

This page provides the EPA interim evaluations of the 2014-2015 milestones for the Chesapeake Bay TMDL. These interim assessments provide a mid-point check on the progress made on the 2014-2015 milestones, recognizing the achievements made in 2014.

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

45 CFR 1623.6 - Interim funding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Interim funding. 1623.6 Section 1623.6 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION SUSPENSION PROCEDURES § 1623.6 Interim funding. (a) Pending the completion of suspension proceedings under this part...

An interim prosthesis program for lower limb amputees: comparison of public and private models of service.

PubMed

Gordon, Robert; Magee, Christopher; Frazer, Anna; Evans, Craig; McCosker, Kathryn

2010-06-01

This study compared the outcomes of an interim mechanical prosthesis program for lower limb amputees operated under a public and private model of service. Over a two-year period, 60 transtibial amputees were fitted with an interim prosthesis as part of their early amputee care. Thirty-four patients received early amputee care under a public model of service, whereby a prosthetist was employed to provide the interim mechanical prosthesis service. The remaining 26 patients received early amputee care under a private model of service, where an external company was contracted to provide the interim mechanical prosthesis service. The results suggested comparable clinical outcomes between the two patient groups. However, the public model appeared to be less expensive with the average labour cost per patient being 29.0% lower compared with the private model. The results suggest that a public model of service may provide a more comprehensive and less expensive interim prosthesis program for lower limb amputees.

Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis.

PubMed

Miller, Frank; Björnsson, Marcus; Svensson, Ola; Karlsten, Rolf

2014-03-01

Dose-finding studies in non-oncology areas are usually conducted in Phase II of the development process of a new potential medicine and it is key to choose a good design for such a study, as the results will decide if and how to proceed to Phase III. The present article has focus on the design of a dose-finding study for pain in osteoarthritis patients treated with the TRPV1 antagonist AZD1386. We describe different design alternatives in the planning of this study, the reasoning for choosing the adaptive design and experiences with conduct and interim analysis. Three alternatives were proposed: one single dose-finding study with parallel design, a programme with a smaller Phase IIa study followed by a Phase IIb dose-finding study, and an adaptive dose-finding study. We describe these alternatives in detail and explain why the adaptive design was chosen for the study. We give insights in design aspects of the adaptive study, which need to be pre-planned, like interim decision criteria, statistical analysis method and setup of a Data Monitoring Committee. Based on the interim analysis it was recommended to stop the study for futility since AZD1386 showed no significant pain decrease based on the primary variable. We discuss results and experiences from the conduct of the study with the novel design approach. Huge cost savings have been done compared to if the option with one dose-finding design for Phase II had been chosen. However, we point out several challenges with this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

78 FR 14487 - Tetrachlorvinphos; Proposed Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

...] Tetrachlorvinphos; Proposed Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: This regulation proposes the extension of the time-limited... related to EPA's extension of the time-limited interim tolerances for the combined residues of the...

78 FR 15880 - Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

... Tetrachlorvinphos; Extension of Time-Limited Interim Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This regulation extends the time-limited interim tolerances for the... . II. Background A detailed summary of the background related to EPA's extension of the time-limited...

24 CFR 115.207 - Consequences of interim certification and certification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consequences of interim certification and certification. 115.207 Section 115.207 Housing and Urban Development Regulations Relating to... ENFORCEMENT AGENCIES Certification of Substantially Equivalent Agencies § 115.207 Consequences of interim...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

46 CFR 308.203 - Amount insured under interim binder.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 8 2012-10-01 2012-10-01 false Amount insured under interim binder. 308.203 Section 308.203 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Protection and Indemnity Insurance § 308.203 Amount insured under interim binder. The...

76 FR 74834 - Interim Staff Guidance on Aging Management Program for Steam Generators

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... NRC staff's evaluation of the suitability of using Revision 3 of the Nuclear Energy Institute's (NEI... NUCLEAR REGULATORY COMMISSION [NRC-2011-0228] Interim Staff Guidance on Aging Management Program for Steam Generators AGENCY: Nuclear Regulatory Commission. ACTION: Interim staff guidance; issuance...

75 FR 58390 - Decision To Evaluate a Petition To Designate a Class of Employees From the Vitro Manufacturing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... Manufacturing. Location: Canonsburg, Pennsylvania. Job Titles and/or Job Duties: All employees who worked in any...: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute...

75 FR 24957 - Decision to Evaluate a Petition to Designate a Class of Employees From BWX Technologies Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

.... Job Titles and/or Job Duties: All Atomic Weapons Employer employees. Period of Employment: January 1... INFORMATION CONTACT: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support...

75 FR 22409 - Decision To Evaluate a Petition To Designate a Class of Employees From the Sandia National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

.... Location: Albuquerque, New Mexico. Job Titles and/or Job Duties: All employees who worked within the... CONTACT: Stuart L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National...

Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients.

PubMed

Bartha, Erzsebet; Davidson, Thomas; Brodtkorb, Thor-Henrik; Carlsson, Per; Kalman, Sigridur

2013-07-09

A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation's main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society's willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society's willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million. If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as 'further research is needed' are replaced with 'further research is cost-effective and 'further funding of a trial is justified'. ClinicalTrials.gov NCT01141894.

Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for Neovascular Age-Related Macular Degeneration in the UK: Interim Results from TERRA.

PubMed

Yang, Yit; Downey, Louise; Mehta, Hemal; Mushtaq, Bushra; Narendran, Niro; Patel, Nishal; Patel, Praveen J; Ayan, Filis; Gibson, Kara; Igwe, Franklin; Jeffery, Pete

2017-06-01

Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. Two cohorts, those switching from a PRN to a T&E regimen ('prior PRN') and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy ('anti-VEGF-naïve') were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and -67.7 μm (95% CI -106.5, -28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Novartis Pharmaceuticals UK Limited.

Added value of dynamical downscaling of winter seasonal forecasts over North America

NASA Astrophysics Data System (ADS)

Tefera Diro, Gulilat; Sushama, Laxmi

2017-04-01

Skillful seasonal forecasts have enormous potential benefits for socio-economic sectors that are sensitive to weather and climate conditions, as the early warning routines could reduce the vulnerability of such sectors. In this study, individual ensemble members of the ECMWF global ensemble seasonal forecasts are dynamically downscaled to produce ensemble of regional seasonal forecasts over North America using the fifth generation Canadian Regional Climate Model (CRCM5). CRCM5 forecasts are initialized on November 1st of each year and are integrated for four months for the 1991-2001 period at 0.22 degree resolution to produce a one-month lead-time forecast. The initial conditions for atmospheric variables are obtained from ERA-Interim reanalysis, whereas the initial conditions for land surface are obtained from a separate ERA-interim driven CRCM5 simulation with spectral nudging applied to the interior domain. The global and regional ensemble forecasts were then verified to investigate the skill and economic benefits of dynamical downscaling. Results indicate that both the global and regional climate models produce skillful precipitation forecast over the southern Great Plains and eastern coasts of the U.S and skillful temperature forecasts over the northern U.S. and most of Canada. In comparison to ECMWF forecasts, CRCM5 forecasts improved the temperature forecast skill over most part of the domain, but the improvements for precipitation is limited to regions with complex topography, where it improves the frequency of intense daily precipitation. CRCM5 forecast also yields a better economic value compared to ECMWF precipitation forecasts, for users whose cost to loss ratio is smaller than 0.5.

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle - an update.

PubMed

Konold, Timm; Arnold, Mark E; Austin, Anthony R; Cawthraw, Saira; Hawkins, Steve A C; Stack, Michael J; Simmons, Marion M; Sayers, A Robin; Dawson, Michael; Wilesmith, John W; Wells, Gerald A H

2012-12-05

To provide information on dose-response and aid in modelling the exposure dynamics of the BSE epidemic in the United Kingdom groups of cattle were exposed orally to a range of different doses of brainstem homogenate of known infectious titre from clinical cases of classical bovine spongiform encephalopathy (BSE). Interim data from this study was published in 2007. This communication documents additional BSE cases, which occurred subsequently, examines possible influence of the bovine prion protein gene on disease incidence and revises estimates of effective oral exposure. Following interim published results, two further cattle, one dosed with 100 mg and culled at 127 months post exposure and the other dosed with 10 mg and culled at 110 months post exposure, developed BSE. Both had a similar pathological phenotype to previous cases. Based on attack rate and incubation period distribution according to dose, the dose estimate at which 50% of confirmed cases would be clinically affected was revised to 0.15 g of the brain homogenate used in the experiment, with a 95% confidence interval of 0.03-0.79 g. Neither the full open reading frame nor the promoter region of the prion protein gene of dosed cattle appeared to influence susceptibility to BSE, but this may be due to the sample size. Oral exposure of cattle to a large range of doses of a BSE brainstem homogenate produced disease in all dose groups. The pathological presentation resembled natural disease. The attack rate and incubation period were dependent on the dose.

Impact of changes in Medicare Home Health care reimbursement on month-to-month Home Health utilization between 1996 and 2001 for a national sample of patients undergoing orthopedic procedures.

PubMed

FitzGerald, John D; Mangione, Carol M; Boscardin, John; Kominski, Gerald; Hahn, Bevra; Ettner, Susan L

2006-09-01

Beginning October 1, 1997, Medicare implemented a series of major changes to the Home Health (HH) reimbursement system. Reimbursements were first significantly reduced under the Interim Payment System (IPS) and then relaxed slightly until implementation of the HH Prospective Payment System (PPS) on October 1, 2000. The objective of this study was to examine the impact of reimbursement policy on HH care utilization. We postulated that in response to the initial changes, there would be reductions in both the probability of any HH use and the number of HH visits per HH user. Under PPS, we postulated there would be further reduction in number of HH visits. We tested whether the policy response differed by HH agency structure and whether subgroups of patients were differentially affected. An interrupted time-series analysis was conducted to examine month-to-month probability of HH selection and the number of HH visits among users. A 100% sample of all Medicare recipients undergoing either elective joint replacement (1.6 million hospital discharges) or surgical management of hip fracture (1.2 million hospital discharges) between January 1996 and December 2001 was selected. Under the IPS, the probability of any HH use and number of visits per episode of HH care fell until the IPS was refined in October 1998. With implementation of the PPS, HH visits fell commensurately. Differentially larger reductions in care were noted at for-profit HH agencies, for the elderly, women, patients receiving state assistance, and patients first discharged to skilled nursing facility or rehabilitation hospitals. Changes in month-to-month utilization of HH services were sharp and well correlated with policy implementation dates, strengthening the evidence for a causal association between policy and patient care in the midst of a sea of concurrent policy changes. Greater reductions in HH visits were noted for vulnerable groups.

Chronic Disease Management for Tobacco Dependence

PubMed Central

Joseph, Anne M.; Fu, Steven S.; Lindgren, Bruce; Rothman, Alexander J.; Kodl, Molly; Lando, Harry; Doyle, Brandon; Hatsukami, Dorothy

2014-01-01

Background Tobacco dependence disorder is a chronic relapsing condition, yet treatment is delivered in discrete episodes of care that yield disappointing long-term quit rates. Methods We conducted a randomized controlled trial from June 1, 2004, through May 31, 2009, to compare telephone-based chronic disease management (1 year; longitudinal care [LC]) with evidence-based treatment (8 weeks; usual care [UC]) for tobacco dependence. A total of 443 smokers each received 5 telephone counseling calls and nicotine replacement therapy by mail for 4 weeks. They were then randomized to UC(2 additional calls) or LC(continued counseling and nicotine replacement therapy for an additional 48 weeks). Longitudinal care targeted repeat quit attempts and interim smoking reduction for relapsers. The primary outcome was 6 months of prolonged abstinence measured at 18 months of follow-up. Results At 18 months, 30.2% of LC participants reported 6 months of abstinence from smoking, compared with 23.5% in UC (unadjusted, P=.13). Multivariate analysis showed that LC (adjusted odds ratio, 1.74; 95% CI, 1.08–2.80), quit attempts in past year (1.75; 1.06–2.89), baseline cigarettes per day (0.95; 0.92–0.99), and smoking in the 14- to 21-day interval post-quit (0.23; 0.14–0.38) predicted prolonged abstinence at 18 months. The LC participants who did not quit reduced smoking more than UC participants (significant only at 12 months). The LC participants received more counseling calls than UC participants (mean, 16.5 vs 5.8 calls; P<.001), longer total duration of counseling (283 vs 117 minutes; P<.001), and more nicotine replacement therapy (4.7 vs 2.4 boxes of patches; P<.001). Conclusion A chronic disease management approach increases both short- and long-term abstinence from smoking. Trial Registration clinicaltrials.gov Identifier: NCT00309296 PMID:22123795

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

30 CFR 827.13 - Coal preparation plants: Interim performance standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Coal preparation plants: Interim performance...-COAL PREPARATION PLANTS NOT LOCATED WITHIN THE PERMIT AREA OF A MINE § 827.13 Coal preparation plants: Interim performance standards. (a) Persons operating or who have operated coal preparation plants after...

75 FR 13484 - Foreign-Trade Zone 22; Temporary/Interim Manufacturing Authority; LG Electronics Mobilecomm USA...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... DEPARTMENT OF COMMERCE [Docket T-1-2010] Foreign-Trade Zones Board Foreign-Trade Zone 22; Temporary/Interim Manufacturing Authority; LG Electronics Mobilecomm USA, Inc. (Cell Phones); Notice of.../ interim manufacturing (T/IM) authority, on behalf of LG Electronics Mobilecomm USA, Inc. (LGEMU), to...

76 FR 37781 - Foreign-Trade Zone 26; Atlanta, GA; Application for Temporary/Interim Manufacturing Authority...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

..., GA; Application for Temporary/ Interim Manufacturing Authority; Makita Corporation of America; (Hand- Held Power Tool and Gasoline/Electric-Powered Garden Product Manufacturing); Buford, GA An application... Georgia Foreign-Trade Zone, Inc., grantee of FTZ 26, requesting temporary/interim manufacturing (T/IM...

Interim Action Proposed Plan for the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit

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

Bradley, J.

2002-06-18

The purpose of this Interim Action Proposed Plan (IAPP) is to describe the preferred interim remedial action for addressing the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit and to provide an opportunity for public input into the remedial action selection process.

The Intentional Interim

ERIC Educational Resources Information Center

Nugent, Patricia A.

2011-01-01

The author spent years in central-office administration, most recently in an interim position. Some interim administrators simply see themselves as placeholders until the real deal is hired, giving the organization the opportunity to coast. There are others who see themselves as change agents and cannot wait to undo or redo what their predecessor…

Presidential Transition: The Experience of Two Community College Interim Presidents

ERIC Educational Resources Information Center

Thompson, Matthew D.

2010-01-01

The purpose of this qualitative case study was to understand the experiences of two community college interim presidents, their characteristics, and how they led institutions following an abrupt presidential departure. There were two fundamental questions framing this research study, 1. How do two interim community college presidents lead…

47 CFR 73.404 - Interim hybrid IBOC DAB operation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RADIO BROADCAST SERVICES Digital Audio Broadcasting § 73.404 Interim hybrid IBOC DAB operation. (a) The... test operation pursuant to § 73.1620, may commence interim hybrid IBOC DAB operation with digital... No. 99-325. FM stations are permitted to operate with hybrid digital effective radiated power equal...

17 CFR 210.10-01 - Interim financial statements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accountant on the review must be filed with the interim financial statements. (e) Filing of other interim... sheets shall include only major captions (i.e., numbered captions) prescribed by the applicable sections... the date of any material accounting change and the reasons for making it. In addition, for filings on...

77 FR 55232 - Japan Lessons-Learned Project Directorate Interim Staff Guidance JLD-ISG-2012-03; Compliance With...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0067] Japan Lessons-Learned Project Directorate Interim...-Learned Project Directorate Interim Staff Guidance; issuance. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing the Final Japan Lessons-Learned Project Directorate (JLD...

78 FR 40199 - Draft Spent Fuel Storage and Transportation Interim Staff Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0140] Draft Spent Fuel Storage and Transportation Interim... Spent Fuel Storage and Transportation Interim Staff Guidance No. 24 (SFST-ISG-24), Revision 0, ``The Use of a Demonstration Program as Confirmation of Integrity for Continued Storage of High Burnup Fuel...

75 FR 66553 - Truth in Lending

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... AGENCY: Board of Governors of the Federal Reserve System. ACTION: Interim final rule; request for public comment. SUMMARY: The Board is publishing for public comment an interim final rule amending Regulation Z (Truth in Lending). The interim rule implements Section 129E of the Truth in Lending Act (TILA), which...

Staff Reactions to Interim Leadership in a Student Affairs Organization

ERIC Educational Resources Information Center

Jones, Robin D.

2011-01-01

Interim leadership appointments in higher education are a common strategy used to fill leadership gaps in executive positions. Because student affairs executives are particularly vulnerable to high turnover rates, interim appointments are becoming more widespread. Even with the prevalence of this trend, little attention has been given to the…

Faculty and Student Views of the Interim Term

ERIC Educational Resources Information Center

Centra, John A.; Sobol, Marion G.

1974-01-01

Evaluations of the interim term or 4-1-4 program at various colleges have been generally favorable. A detailed evaluation of the Rider College interim study program based on faculty and student reports indicated that the more nontraditionally oriented courses were rated higher than the more traditional offerings. (Editor/PG)

12 CFR 541.18 - Interim Federal savings association.

Code of Federal Regulations, 2010 CFR

2010-01-01

... an existing savings and loan holding company or to facilitate any other transaction the Office may... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Interim Federal savings association. 541.18... REGULATIONS AFFECTING FEDERAL SAVINGS ASSOCIATIONS § 541.18 Interim Federal savings association. The term...

15 CFR 904.322 - Interim action.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Interim action. 904.322 Section 904... Sanctions and Denials Permit Sanction for Violations § 904.322 Interim action. (a) To protect marine resources during the pendency of an action under this subpart, in cases of willfulness, or as otherwise...

15 CFR 904.322 - Interim action.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Interim action. 904.322 Section 904... Sanctions and Denials Permit Sanction for Violations § 904.322 Interim action. (a) To protect marine resources during the pendency of an action under this subpart, in cases of willfulness, or as otherwise...

Into the Sunset: Reflections of an Interim Administrator.

ERIC Educational Resources Information Center

Marlowe, John

2000-01-01

One advantage to an interim administrative position is that the public cuts short-timers a little slack. Temporary administrators can learn on the job and become experts on specialized subjects. Personnel issues demand more time than interims possess. Such positions usually do not turn into long-term contracts. (MLH)

PCoD Lite - Using an Interim PCoD Protocol to Assess the Effects of Disturbance Associated with US Navy Exercises on Marine Mammal Populations

DTIC Science & Technology

2015-09-30

1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. PCoD Lite - Using an Interim PCoD Protocol to Assess...US National Research Council (NRC 2005). Here, we provide an insight into how the Interim PCoD approach (Harwood et al. 2014, King et al. 2015...illustrate how the interim PCoD protocol can be used to inform the process of determining whether or not Navy activities are likely to have an impact on

[A pilot clinical study of immediate provisionalization with a chairside computer aided design and computer aided manufacture monolithic crown for single tooth immediate implant placement].

PubMed

Tian, J H; Di, P; Lin, Y; Zhang, Y; Wei, D H; Cui, H Y

2017-01-09

Objective: To evaluate the primary clinical outcomes of immediate provisionalization with a monolithic crown utilizing a novel chairside computer aided design and computer aided manufacture (CAD/CAM) workflow for single tooth immediate implant placement. Methods: This pilot study was a prospective within-subjects design. Thirteen consecutive patients were included and diagnosed with untreatable single incisor or premolar with fine general and local anatomical conditions. The trial was conducted at Department of Implantology, Peking University School and Hospital of Stomatology, Beijing, between January 2016 and June 2016. The teeth were extracted atraumatically and implants were immediately placed in the fresh sockets. Two screw-retained interim crowns were fabricated for the same site utilizing different workflows, a monolithic lithium disilicate (LS2) crown produced by CEREC (Sirona, Germany) chairside CAD/CAM system (CER group) and a manually fabricated resin crown utilizing conventional workflow (CONV group) respectively. The patients were blinded to the group allocation of the two interim crowns. After the clinical try-in for both crowns in a randomized sequence, the patients ' level of satisfaction was assessed with a virtual analogue scale (VAS) questionnaire. The restorations chosen by patients themselves were seated in the implants by one experienced prosthodontist. The accuracy, aesthetic effect and clinical time consumption of both groups were compared. Statistical analyses were performed with the Wilcoxon signed rank test. Results: All patients were treated with atraumatic tooth extraction, immediate implant placement using flapless surgery and immediate provisionalization in a single visit. The interim crowns of both groups could be fitted with or without slight adjustments. For each patient, the interim crown of CER group was chosen to be seated with a relatively higher VAS result. The white esthetic score (WES) results demonstrated no statistically significant difference between CER group (7.5±1.1) and CONV group (7.9±0.9) ( P> 0.05). The mean total work time was significantly different resulting in (131.9±5.0) min for CER group and (205.2±6.3) min( P< 0.05). The major difference lied in the laboratory work time, resulting in (113.5±6.3) min for CER group which was significantly shorter than (185.6±6.6) min for CONV group. As for impression taking time, the CER group (7.5±0.8) min was significantly shorter than CONV group (11.7± 1.1) min ( P< 0.05). However, analysis for clinical adjustment time showed a significantly longer time for CER group [(11.0±2.1) min vs (8.0±2.8) min, P< 0.05]. After 3-6 months of observation, the overall survival rate was 100%. Screw loosening occurred in 4 patients and was tightened again. No other major complication soccurred. Conclusions: The full digital workflow utilizing CEREC chairside CAD/CAM system to fabricate interim crowns after immediate implant placement in one single visit was feasible. It was more time-efficient and could effectively shorten the laboratory work time compared to the conventional workflow. Patients demonstrated high satisfaction and there was no statistical difference in WES results compared to the conventional workflow. Favorable clinical outcomes were gained in this short-term follow-up study.

The Analytic Onion: Examining Training Issues from Different Levels of Analysis. Interim Technical Paper for Period July 1989-June 1991.

ERIC Educational Resources Information Center

Lamb, Theodore A.; Chin, Keric B. O.

This paper proposes a conceptual framework based on different levels of analysis using the metaphor of the layers of an onion to help organize and structure thinking on research issues concerning training. It discusses the core of the "analytic onion," the biological level, and seven levels of analysis that surround that core: the individual, the…

The Similarity of Job Types Reported from Two Independent Analyses of Occupational Data. Interim Report. April 2, 1973-October 12, 1973.

ERIC Educational Resources Information Center

Watson, William J.

Occupational analysts using Comprehensive Occupational Data Analysis Programs (CODAP) make subjective decisions at various stages in their analysis of an occupation. The possibility exists that two different analysts could reach different conclusions in analyzing an occupation, and thereby provide divergent guidance to management. Two analysts,…

Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment.

PubMed

Okada, Masaya; Imagawa, Jun; Tanaka, Hideo; Nakamae, Hirohisa; Hino, Masayuki; Murai, Kazunori; Ishida, Yoji; Kumagai, Takashi; Sato, Seiichi; Ohashi, Kazuteru; Sakamaki, Hisashi; Wakita, Hisashi; Uoshima, Nobuhiko; Nakagawa, Yasunori; Minami, Yosuke; Ogasawara, Masahiro; Takeoka, Tomoharu; Akasaka, Hiroshi; Utsumi, Takahiko; Uike, Naokuni; Sato, Tsutomu; Ando, Sachiko; Usuki, Kensuke; Mizuta, Syuichi; Hashino, Satoshi; Nomura, Tetsuhiko; Shikami, Masato; Fukutani, Hisashi; Ohe, Yokiko; Kosugi, Hiroshi; Shibayama, Hirohiko; Maeda, Yasuhiro; Fukushima, Toshihiro; Yamazaki, Hirohito; Tsubaki, Kazuo; Kukita, Toshimasa; Adachi, Yoko; Nataduka, Toshiki; Sakoda, Hiroto; Yokoyama, Hisayuki; Okamoto, Takahiro; Shirasugi, Yukari; Onishi, Yasushi; Nohgawa, Masaharu; Yoshihara, Satoshi; Morita, Satoshi; Sakamoto, Junichi; Kimura, Shinya

2018-05-01

We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ + T-cell and CD4 + regulatory T-cell (CD25 + CD127 low ) counts before discontinuation correlated significantly with successful therapy discontinuation. These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

76 FR 42631 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition To List Pinus...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

...We, the U.S. Fish and Wildlife Service (Service), announce a 12-month finding on a petition to list Pinus albicaulis (whitebark pine) as threatened or endangered and to designate critical habitat under the Endangered Species Act of 1973, as amended (Act). After review of all available scientific and commercial information, we find that listing P. albicaulis as threatened or endangered is warranted. However, currently listing P. albicaulis is precluded by higher priority actions to amend the Lists of Endangered and Threatened Wildlife and Plants. Upon publication of this 12-month petition finding, we will add P. albicaulis to our candidate species list. We will develop a proposed rule to list P. albicaulis as our priorities and funding will allow. We will make any determination on critical habitat during development of the proposed listing rule. In any interim period, we will address the status of the candidate taxon through our annual Candidate Notice of Review.

Remedy Selection and Land Use at Federal Facilities

EPA Pesticide Factsheets

Analysis of approximately 98 percent of the interim and final source control Records of Decision signed at Federal Facilities on the NPL from the beginning of Superfund through August 1995. PB96-963309. EPA/540/R-96/020. August 1996

75 FR 24957 - Decision to Evaluate a Petition to Designate a Class of Employees From the Los Alamos National...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... Laboratory. Location: Los Alamos, New Mexico. Job Titles and/or Job Duties: All employees of the Department.... Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute for...

75 FR 51815 - Decision To Evaluate a Petition To Designate a Class of Employees From the Norton Company...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

..., Massachusetts. Job Titles and/or Job Duties: All employees who worked in any building or area. Period of..., Interim Director, Division of Compensation Analysis and Support, National Institute for Occupational...

Bend case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

2000-01-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and aerial photos, gro...

McMinnville case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

1999-12-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed : the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and : aerial photos,...

Precipitation and floodiness: forecasts of flood hazard at the regional scale

NASA Astrophysics Data System (ADS)

Stephens, Liz; Day, Jonny; Pappenberger, Florian; Cloke, Hannah

2016-04-01

In 2008, a seasonal forecast of an increased likelihood of above-normal rainfall in West Africa led the Red Cross to take early humanitarian action (such as prepositioning of relief items) on the basis that this forecast implied heightened flood risk. However, there are a number of factors that lead to non-linearity between precipitation anomalies and flood hazard, so in this presentation we use a recently developed global-scale hydrological model driven by the ERA-Interim/Land precipitation reanalysis (1980-2010) to quantify this non-linearity. Using these data, we introduce the concept of floodiness to measure the incidence of floods over a large area, and quantify the link between monthly precipitation, river discharge and floodiness anomalies. Our analysis shows that floodiness is not well correlated with precipitation, demonstrating the problem of using seasonal precipitation forecasts as a proxy for forecasting flood hazard. This analysis demonstrates the value of developing hydrometeorological forecasts of floodiness for decision-makers. As a result, we are now working with the European Centre for Medium-Range Weather Forecasts and the Joint Research Centre, as partners of the operational Global Flood Awareness System (GloFAS), to implement floodiness forecasts in real-time.

Comparison of surface sensible and latent heat fluxes over the Tibetan Plateau from reanalysis and observations

NASA Astrophysics Data System (ADS)

Xie, Jin; Yu, Ye; Li, Jiang-lin; Ge, Jun; Liu, Chuan

2018-02-01

Surface sensible and latent heat fluxes (SH and LE) over the Tibetan Plateau (TP) have been under research since 1950s, especially for recent several years, by mainly using observation, reanalysis, and satellite data. However, the spatiotemporal changes are not consistent among different studies. This paper focuses on the spatiotemporal variation of SH and LE over the TP from 1981 to 2013 using reanalysis data sets (ERA-Interim, JRA-55, and MERRA) and observations. Results show that the spatiotemporal changes from the three reanalysis data sets are significantly different and the probable causes are discussed. Averaged for the whole TP, both SH and LE from MERRA are obviously higher than the other two reanalysis data sets. ERA-Interim shows a significant downward trend for SH and JRA-55 shows a significant increase of LE during the 33 years with other data sets having no obvious changes. By comparing the heat fluxes and some climate factors from the reanalysis with observations, it is found that the differences of heat fluxes among the three reanalysis data sets are closely related to their differences in meteorological conditions as well as the different parameterizations for surface transfer coefficients. In general, the heat fluxes from the three reanalysis have a better representation in the western TP than that in the eastern TP under inter-annual scale. While in terms of monthly variation, ERA-Interim may have better applicability in the eastern TP with dense vegetation conditions, while SH of JRA-55 and LE of MERRA are probably more representative for the middle and western TP with poor vegetation conditions.

Developing a concept for a national used fuel interim storage facility in the United States

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

Lewis, Donald Wayne

2013-07-01

In the United States (U.S.) the nuclear waste issue has plagued the nuclear industry for decades. Originally, spent fuel was to be reprocessed but with the threat of nuclear proliferation, spent fuel reprocessing has been eliminated, at least for now. In 1983, the Nuclear Waste Policy Act of 1982 [1] was established, authorizing development of one or more spent fuel and high-level nuclear waste geological repositories and a consolidated national storage facility, called a 'Monitored Retrievable Storage' facility, that could store the spent nuclear fuel until it could be placed into the geological repository. Plans were under way to buildmore » a geological repository, Yucca Mountain, but with the decision by President Obama to terminate the development of Yucca Mountain, a consolidated national storage facility that can store spent fuel for an interim period until a new repository is established has become very important. Since reactor sites have not been able to wait for the government to come up with a storage or disposal location, spent fuel remains in wet or dry storage at each nuclear plant. The purpose of this paper is to present a concept developed to address the DOE's goals stated above. This concept was developed over the past few months by collaboration between the DOE and industry experts that have experience in designing spent nuclear fuel facilities. The paper examines the current spent fuel storage conditions at shutdown reactor sites, operating reactor sites, and the type of storage systems (transportable versus non-transportable, welded or bolted). The concept lays out the basis for a pilot storage facility to house spent fuel from shutdown reactor sites and then how the pilot facility can be enlarged to a larger full scale consolidated interim storage facility. (authors)« less

75 FR 7591 - Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-SFUND-2009-0907; FRL-9114-6] RIN 2050-ZA05 Guidance on Recommended Interim Preliminary Remediation Goals for Dioxin in Soil at CERCLA and RCRA Sites; Extension of... Interim Preliminary Remediation Goals for Dioxin in Soil at Comprehensive Environmental Response...

Do Interim Assessments Reduce the Race and SES Achievement Gaps?

ERIC Educational Resources Information Center

Konstantopoulos, Spyros; Li, Wei; Miller, Shazia R.; van der Ploeg, Arie

2017-01-01

The authors examined differential effects of interim assessments on minority and low socioeconomic status students' achievement in Grades K-6. They conducted a large-scale cluster randomized experiment in 2009-2010 to evaluate the impact of Indiana's policy initiative introducing interim assessments statewide. The authors used 2-level models to…

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

75 FR 54526 - Defense Federal Acquisition Regulation Supplement; Payment of Costs Prior to Definitization...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... in 48 CFR Part 217 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the... interim rule. Therefore, DoD is finalizing the interim rule without change. This rule was not subject to...

76 FR 43260 - Foreign-Trade Zone 72-Indianapolis, IN; Application for Temporary/Interim Manufacturing Authority...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...--Indianapolis, IN; Application for Temporary/Interim Manufacturing Authority; Brevini Wind USA, Inc. (Wind... temporary/interim manufacturing (T/IM) authority within FTZ 72 at the Brevini Wind USA, Inc. (Brevini... requested authority to produce wind turbine gear boxes (HTSUS 8483.40, duty rate: 2.5%). Foreign components...

75 FR 60436 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it is releasing an interim...

75 FR 24667 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it released an interim change...

75 FR 10476 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it released an interim change...

76 FR 776 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it is releasing an interim...

75 FR 15420 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) NO. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it will release an interim...

76 FR 59119 - Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... DEPARTMENT OF DEFENSE Department of the Army Interim Change to the Military Freight Traffic Unified Rules Publication (MFTURP) No. 1 AGENCY: Department of the Army, DoD. SUMMARY: The Military Surface Deployment and Distribution Command (SDDC) is providing notice that it has released an interim...

Can Interim Assessments Be Used for Instructional Change? Policy Brief. RB-51

ERIC Educational Resources Information Center

Goertz, Margaret E.; Olah, Leslie Nabors; Riggan, Matthew

2009-01-01

The purpose of this exploratory study was to examine the use of interim assessments and the policy supports that promote their use to change instruction, focusing on elementary school mathematics. The authors use the term "interim assessments" to refer to assessments that: a) evaluate student knowledge and skills, typically within a…

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2011 CFR

2011-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... 40 Protection of Environment 26 2011-07-01 2011-07-01 false EPA Interim Primary Drinking Water... Water Standards Parameter Maximum level (mg/l) Arsenic 0.05 Barium 1.0 Cadmium 0.01 Chromium 0.05...

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2010 CFR

2010-07-01

...) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT... 40 Protection of Environment 25 2010-07-01 2010-07-01 false EPA Interim Primary Drinking Water... Water Standards Parameter Maximum level (mg/l) Arsenic 0.05 Barium 1.0 Cadmium 0.01 Chromium 0.05...

33 CFR 96.360 - Interim Safety Management Certificate: what is it and when can it be used?

Code of Federal Regulations, 2010 CFR

2010-07-01

... section, when— (1) The company's valid Document of Compliance certificate or Interim Document of Compliance certificate applies to that vessel type; (2) The company's safety management system for the vessel... to the responsible person or their company. (b) An Interim Safety Management Certificate is valid for...

76 FR 15028 - Airport Improvement Program (AIP): Interim Policy Regarding Access to Airports From Residential...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... resolution. The goal of the interim policy is to strike a careful balance by accommodating residential... will allow the agency to complete a separate, ongoing general aviation airport study that is analyzing the federally assisted general aviation airport system. The interim policy adopts the changes proposed...

18 CFR 300.20 - Interim acceptance and review of Bonneville Power Administration rates.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Interim acceptance and review of Bonneville Power Administration rates. 300.20 Section 300.20 Conservation of Power and Water... Director of the Office of Energy Market Regulation; or (ii) Deny the Administrator's interim rate request...

42 CFR 417.572 - Budget and enrollment forecast and interim reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Budget and enrollment forecast and interim reports... PLANS, AND HEALTH CARE PREPAYMENT PLANS Medicare Payment: Cost Basis § 417.572 Budget and enrollment forecast and interim reports. (a) Annual submittal. The HMO or CMP must submit an annual operating budget...

78 FR 5830 - Draft Environmental Assessment and Proposed Habitat Conservation Plan for the Interim Operations...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... Operations of PacifiCorp's Klamath Hydroelectric Project on the Klamath River, Klamath County, OR, and... Environmental Policy Act (NEPA) for the interim operations of the Klamath Hydroelectric Project in [[Page 5831... habitats upon which they depend, resulting from the interim operations of the Klamath Hydroelectric Project...

40 CFR Appendix III to Part 265 - EPA Interim Primary Drinking Water Standards

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false EPA Interim Primary Drinking Water Standards III Appendix III to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Pt....

75 FR 65528 - Membership of the National Science Board's Senior Executive Service Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

...: Comments should be addressed to Interim Director, Division of Human Resource Management and Chief Human.... Judith S. Sunley, Interim Director, Division of Human Resource Management and Chief Human Capital Officer..., Interim Director, Division of Human Resource Management and Chief Human Capital Officer. [FR Doc. 2010...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

46 CFR 308.6 - Period of interim binders, updating application information and new applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information and new applications. 308.6 Section 308.6 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.6 Period of interim binders, updating... interim binders are required to notify the American War Risk Agency annually, by June 30th, of any change...

77 FR 15818 - License Renewal Interim Staff Guidance LR-ISG-2011-05: Ongoing Review of Operating Experience

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...-05: Ongoing Review of Operating Experience AGENCY: Nuclear Regulatory Commission. ACTION: Interim... License Renewal Interim Staff Guidance (LR-ISG), LR-ISG-2011-05, ``Ongoing Review of Operating Experience... industry-wide operating experience as an attribute of aging management programs used at nuclear power...

31 CFR 50.7 - Special Rules for Interim Guidance Safe Harbors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Special Rules for Interim Guidance Safe Harbors. 50.7 Section 50.7 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM General Provisions § 50.7 Special Rules for Interim Guidance Safe Harbors...

Tabulations of ambient ozone data obtained by GASP (Global Air Sampling Program) airliners, March 1975 to July 1979

NASA Technical Reports Server (NTRS)

Jasperson, W. H.; Holdeman, J. D.

1984-01-01

Tabulations are given of GASP ambient ozone mean, standard deviation, median, 84th percentile, and 98th percentile values, by month, flight level, and geographical region. These data are tabulated to conform to the temporal and spatial resolution required by FAA Advisory Circular 120-38 (monthly by 2000 ft in altitude by 5 deg in latitude) for climatological data used to show compliance with cabin ozone regulations. In addition seasonal x 10 deg latitude tabulations are included which are directly comparable to and supersede the interim GASP ambient ozone tabulations given in appendix B of FAA-EE-80-43 (NASA TM-81528). Selected probability variations are highlighted to illustrate the spatial and temporal variability of ambient ozone and to compare results from the coarse and fine grid analyses.

A Conservative Method of Retaining an Interim Obturator for a Total Maxillectomy Patient

PubMed Central

Bettie, Nirmal Famila

2017-01-01

Interim obturators are indicated during the postsurgical phases. It promotes surgical healing and serves as a temporary prosthesis to rehabilitate a patient with intra-oral surgical defect. Retention is gained by wiring, surgical suturing, and other noninvasive methods to enable functional rehabilitation and easy replacement with a permanent obturator. Interim obturators serve as an easy guide for replacing with definitive obturators by indicating prosthesis extensions and the required method of retention. A more conservative and noninvasive method of retaining an interim obturator for a maxillectomy patient is described in this case report. PMID:29284985

A Conservative Method of Retaining an Interim Obturator for a Total Maxillectomy Patient.

PubMed

Bettie, Nirmal Famila

2017-11-01

Interim obturators are indicated during the postsurgical phases. It promotes surgical healing and serves as a temporary prosthesis to rehabilitate a patient with intra-oral surgical defect. Retention is gained by wiring, surgical suturing, and other noninvasive methods to enable functional rehabilitation and easy replacement with a permanent obturator. Interim obturators serve as an easy guide for replacing with definitive obturators by indicating prosthesis extensions and the required method of retention. A more conservative and noninvasive method of retaining an interim obturator for a maxillectomy patient is described in this case report.

Relationships between High Impact Tropical Rainfall Events and Environmental Conditions

NASA Astrophysics Data System (ADS)

Painter, C.; Varble, A.; Zipser, E. J.

2017-12-01

While rainfall increases as moisture and vertical motion increase, relationships between regional environmental conditions and rainfall event characteristics remain more uncertain. Of particular importance are long duration, heavy rain rate, and significant accumulation events that contribute sizable fractions of overall precipitation over short time periods. This study seeks to establish relationships between observed rainfall event properties and environmental conditions. Event duration, rain rate, and rainfall accumulation are derived using the Tropical Rainfall Measuring Mission (TRMM) 3B42 3-hourly, 0.25° resolution rainfall retrieval from 2002-2013 between 10°N and 10°S. Events are accumulated into 2.5° grid boxes and matched to monthly mean total column water vapor (TCWV) and 500-hPa vertical motion (omega) in each 2.5° grid box, retrieved from ERA-interim reanalysis. Only months with greater than 3 mm/day rainfall are included to ensure sufficient sampling. 90th and 99th percentile oceanic events last more than 20% longer and have rain rates more than 20% lower than those over land for a given TCWV-omega condition. Event duration and accumulation are more sensitive to omega than TCWV over oceans, but more sensitive to TCWV than omega over land, suggesting system size, propagation speed, and/or forcing mechanism differences for land and ocean regions. Sensitivities of duration, rain rate, and accumulation to TCWV and omega increase with increasing event extremity. For 3B42 and ERA-Interim relationships, the 90th percentile oceanic event accumulation increases by 0.93 mm for every 1 Pa/min change in rising motion, but this increases to 3.7 mm for every 1 Pa/min for the 99th percentile. Over land, the 90th percentile event accumulation increases by 0.55 mm for every 1 mm increase in TCWV, whereas the 99th percentile increases by 0.90 mm for every 1 mm increase in TCWV. These changes in event accumulation are highly correlated with changes in event duration. Relationships between 3B42 event properties and ERA-Interim environmental conditions are currently being evaluated using the MERRA-2 reanalysis and two years of 30-minute, 0.1° Integrated Multi-satellitE Retrievals for GPM (IMERG) data. If results remain consistent, they may be valuable for evaluating weather and climate models.

A Vectorized ’Nearest-Neighbors’ Algorithm of Order N Using a Monotonic Logical Grid

DTIC Science & Technology

1985-05-29

Computational Phy’sics 0 4 May 29 , 1985 This work was supported by the Office of Naval Research. . ~ Q~JUN 1719851- * NAVAL RESEARCH LABORATORY * lit...YE ’.ARK:NGS UNCLASSIFIED_______________ _____ K -. A R, ~ CA7,ON 4, 71CO1, 3 :)-S7R,9U-ON AdA,.A3:L ’Y OF REPOR7Io - EC..ASi.’ CA27 ON., DOWNGAZING...Year. Month. Day) 5 PAGE COUNT Interim FROM -____ Toi__ 1985 May 29 50 𔄀 SuPPILSMENTARY NOTATION This work was supported by the Office of Naval

Large Area Crop Inventory Experiment (LACIE). First interim phase 3 evaluation report. [Great Plains and U.S.S.R.

NASA Technical Reports Server (NTRS)

1978-01-01

The author has identified the following significant results. LACIE acreage estimates were in close agreement with SRS estimates, and an operational system with a 14 day LANDSAT data turnaround could have produced an accurate acreage estimate (one which satisfied the 90/90 criterion) 1 1/2 to 2 months before harvest. Low yield estimates, resulting from agromet conditions not taken into account in the yield models, caused production estimates to be correspondingly low. However, both yield and production estimates satisfied the LACIE 90/90 criterion for winter wheat in the yardstick region.

7 CFR 1738.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... means the pro forma financial analysis prepared by the applicant, and acceptable to RUS, to determine... years estimated in the feasibility study for completion of the construction covered by the loan... the RE Act to each eligible entity. Interim construction means the construction, improvement, or...

7 CFR 1738.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... means the pro forma financial analysis prepared by the applicant, and acceptable to RUS, to determine... years estimated in the feasibility study for completion of the construction covered by the loan... the RE Act to each eligible entity. Interim construction means the construction, improvement, or...

75 FR 14443 - Decision To Evaluate a Petition To Designate a Class of Employees for Revere Copper and Brass in...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

.... Job Titles and/or Job Duties: Extruders and Shapes Specialists who worked in the Rod and Shape Mill... L. Hinnefeld, Interim Director, Division of Compensation Analysis and Support, National Institute...

Grants Pass case study : indirect land use and growth impacts : interim report

DOT National Transportation Integrated Search

1999-08-01

To improve environmental analysis of indirect land use impacts of highway capacity improvements, this study analyzed the land use and growth patterns of 20 Oregon communities over 20 years. Using a Geographic Information System and aerial photos, gro...

40 CFR 265.113 - Closure; time allowed for closure.

Code of Federal Regulations, 2010 CFR

2010-07-01

... includes an amended waste analysis plan, ground-water monitoring and response program, human exposure....113 Section 265.113 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND...

Land Use Management for Solid Waste Programs

ERIC Educational Resources Information Center

Brown, Sanford M., Jr.

1974-01-01

The author discusses the problems of solid waste disposal and examines various land use management techniques. These include the land use plan, zoning, regionalization, land utilities, and interim use. Information concerning solid waste processing site zoning and analysis is given. Bibliography included. (MA)

Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data

PubMed Central

Araújo, Alex Maurício

2017-01-01

This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area. PMID:28817731

Wave energy resource of Brazil: An analysis from 35 years of ERA-Interim reanalysis data.

PubMed

Espindola, Rafael Luz; Araújo, Alex Maurício

2017-01-01

This paper presents a characterization of the wave power resource and an analysis of the wave power output for three (AquaBuoy, Pelamis and Wave Dragon) different wave energy converters (WEC) over the Brazilian offshore. To do so it used a 35 years reanalysis database from the ERA-Interim project. Annual and seasonal statistical analyzes of significant height and energy period were performed, and the directional variability of the incident waves were evaluated. The wave power resource was characterized in terms of the statistical parameters of mean, maximum, 95th percentile and standard deviation, and in terms of the temporal variability coefficients COV, SV e MV. From these analyses, the total annual wave power resource available over the Brazilian offshore was estimated in 89.97 GW, with largest mean wave power of 20.63 kW/m in the southernmost part of the study area. The analysis of the three WEC was based in the annual wave energy output and in the capacity factor. The higher capacity factor was 21.85% for Pelamis device at the southern region of the study area.

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

50 CFR 660.720 - Interim protection for sea turtles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Interim protection for sea turtles. 660... Migratory Fisheries § 660.720 Interim protection for sea turtles. (a) Until the effective date of §§ 660.707... harvest of swordfish (Xiphias gladius) using longline gear deployed on the high seas of the Pacific Ocean...

49 CFR 37.169 - Interim requirements for over-the-road bus service operated by private entities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Interim requirements for over-the-road bus service... Interim requirements for over-the-road bus service operated by private entities. (a) Private entities operating over-the-road buses, in addition to compliance with other applicable provisions of this part...

76 FR 48197 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... assessable professional reported or required to be reported by a municipal advisor to the MSRB on Form A-11... Assessment and Form A-11- Interim. For purposes of the interim assessment, an assessable professional of a...-Interim as an assessable professional any associated person (i) Who otherwise qualifies as an assessable...

78 FR 53038 - Interim Final Determination to Stay and Defer Sanctions; California; San Joaquin Valley

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R09-OAR-2013-0534; FRL-9900-36-Region 9.... Environmental Protection Agency (EPA). ACTION: Interim final rule. SUMMARY: EPA is making an interim [email protected] . Mail or deliver: Frances Wicher (AIR-2), U.S. Environmental Protection Agency Region 9...